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Journal of Drug Delivery Science and Technology (17732247) 112
GABAB receptors are key regulators of neuronal excitability via slow inhibitory mechanisms. Their downregulation in cerebral ischemic stroke impairs excitotoxicity and neuronal death. Quercetin (QC), a well-known flavonoid, has neuroprotective properties but is limited by poor bioavailability and low water solubility. To overcome these restrictions, quercetin was conjugated with superparamagnetic iron oxide nanoparticles (QCSPIONs) and their effectiveness as a treatment was evaluated in an aged rat model of transient middle cerebral artery occlusion (tMCAO). Animals were given QC, QCSPIONs, and vehicle orally for 14 days after reperfusion following exposure to tMCAO. Neurological deficits, infarct volume, brain edema, sensory-motor function, learning, memory, and hippocampal mRNA expression of GABAB receptor subunits, CHOP, Bax, and Bcl-2 were evaluated. Both QC and QCSPIONs significantly enhanced neurological function, reduced infarct volume, alleviated brain edema, and improved cognitive recovery. QCSPIONs showed higher efficacy in comparison to free QC, as evidenced by better performance in behavioral tests, and greater modulation of gene expression. Treatment with QC and QCSPIONs reduced CHOP and the Bax/Bcl-2 ratio while increasing the mRNA expression of GABAB receptor subunits and Bcl-2, suggesting anti-apoptotic and neuroprotective properties. These findings propose that QCSPIONs increase neuroprotection against excitotoxicity by modulating GABAB receptor and CHOP mRNA expression in aged rats following ischemic stroke. Our study highlights the therapeutic potential of QCSPIONs as a novel strategy for moderating brain injury and improving functional recovery after cerebral ischemia/reperfusion. © 2025 Elsevier B.V.
Oncology Reviews (19705557) 18
Background: Malignant gliomas are known with poor prognosis and low rate of survival among brain tumors. Resection surgery is followed by chemotherapy and radiotherapy in treatment of gliomas which is known as the conventional treatment. However, this treatment method results in low survival rate. Vaccination has been suggested as a type of immunotherapy to increase survival rate of glioma patients. Different types of vaccines have been developed that are mainly classified in two groups including peptide vaccines and cell-based vaccines. However, there are still conflicts about which type of vaccines is more efficient for malignant glioma treatment. Methods: Phase Ⅰ/Ⅱ clinical trials which compared the efficacy and safety of various vaccines with conventional treatments were searched in databases through November 2022. Overall survival (OS) rate, progression free survival (PFS), and OS duration were used for calculation of pooled risk ratio (RR). In addition, fatigue, headache, nausea, diarrhea, and flu-like syndrome were used for evaluating the safety of vaccines therapy in glioma patients. Results: A total of twelve articles were included in the present meta-analysis. Comparison of OS rate between vaccinated groups and control groups who underwent only conventional treatments showed a significant increase in OS rate in vaccinated patients (I2 = 0%, RR = 11.17, 95% CI: 2.460–50.225). PFS rate was better in vaccinated glioma patients (I2 = 83%, RR = 2.87, 95% CI: 1.63–5.03). Assessment of safety demonstrated that skin reaction (I2 = 0.0%, RR = 3.654; 95% CI: 1.711–7.801, p-value = 0.0058) and flu-like syndrome were significantly more frequent adverse effects win vaccinated groups compared to the control group. Subgroup analysis also showed that vaccination leads to better OS duration in recurrent gliomas than primary gliomas, and in LGG than HGG (p-value = 0). On the other hand, personalized vaccines showed better OS duration than non-personalized vaccines (p-value = 0). Conclusion: Vaccination is a type of immunotherapy which shows promising efficacy in treatment of malignant glioma patients in terms of OS, PFS and duration of survival. In addition, AFTV, peptide, and dendritic cell-based vaccines are among the most efficient vaccines for gliomas. Personalized vaccines also showed considerable efficacy for glioma treatments. Copyright © 2024 Amanzadeh Jajin, Oraee Yazdani, Zali and Esmaeili.
Esmaeili, A. ,
Ebrahimpour, S. ,
Hefshejani, K.F. ,
Esmaeili, A. Archives of Oral Biology (00039969) 159
Objective: We investigated the effects of molar tooth shortening on the mRNA expression of the AβPP/BACE1, BDNF/TrkB, and Bax/Bcl-2 signaling pathways in the Wistar male rat hippocampal regions. Design: Four groups (n = 5 per group) of male Wistar rats (control, SRM (shortened right molar), SLM (shortened left molar), and SBM (shortened bilateral molar)) were used. RNA was isolated from the hippocampus and transformed into cDNA. Real-time quantitative PCR was used to evaluate the mRNA expression levels of AβPP, BACE1, Bax, Bcl-2, BDNF, and TrkB. Results: Differential mRNA expression was observed in rat groups. SBM significantly upregulated the AβPP, BACE1, and Bax mRNA expressions, whereas the expression levels of Bcl-2, BDNF, and TrkB were decreased. SRM and SLM approximately had the same effect on the expression enhancement of AβPP, BACE1, and Bax; however, SRM was more effective than SLM in increasing the expression of these genes. Conclusions: Symmetrical molar teeth shortening affected the mRNA expression of AβPP and BACE1, which is related to learning and memory dysfunction. © 2024 Elsevier Ltd
Ageing Research Reviews (15681637) 97
Parkinson's disease is predominantly caused by dopaminergic neuron loss in the substantia nigra pars compacta and the accumulation of alpha-synuclein protein. Though the general consensus is that several factors, such as aging, environmental factors, mitochondrial dysfunction, accumulations of neurotoxic alpha-synuclein, malfunctions of the lysosomal and proteasomal protein degradation systems, oxidative stress, and neuroinflammation, are involved in the neurodegeneration process of Parkinson's disease, the precise mechanism by which all of these factors are triggered remains unknown. Typically, neurotoxic compounds such as rotenone, 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl 4-phenyl pyridinium (mpp+), paraquat, and maneb are used to Preclinical models of Parkinson's disease Ferulic acid is often referred to by its scientific name, 4-hydroxy-3-methoxycinnamic acid (C10H10O4), and is found naturally in cereals, fruits, vegetables, and bee products. This substance exhibits neuroprotective effects against Parkinson's disease because of its intriguing potential, which includes anti-inflammatory and antioxidant qualities. This review goes into additional detail about Parkinson's disease and the neuroprotective properties of ferulic acid that may help prevent the condition. © 2024 Elsevier B.V.
Environmental Research (00139351) 232
Neurogenesis is decreased in the absence of nerve growth factor (NGF). It would be beneficial to discover substances that stimulate neurogenesis without NGF, given the high molecular weight and brief half-life of NGF. This work aims to assess the neurogenesis of ginger extract (GE) combined with superparamagnetic iron oxide nanoparticles (SPIONs) without NGF. Based on our research, GE and SPIONs start neurogenesis before NGF. In comparison to the control group, GE and SPIONs dramatically reduced the length and quantity of neurites, according to statistical analysis. Our findings also indicated that SPIONs and ginger extract together had an additive impact on one another. The total number significantly increased with the addition of GE and nanoparticles. In comparison to NGF, the mixture of GE and nanoparticles significantly enhanced the total number of cells with neurites (by about 1.2-fold), the number of branching points (by about 1.8-fold), and the length of neurites. The difference between ginger extract and nanoparticles with NGF was significant (about 3.5-fold), particularly in the case of cells with one neurite. The results of this study point to the possibility of treating neurodegenerative disorders via the combination of GE and SPIONs without NGF. © 2023 Elsevier Inc.
Chamgordani, M.K. ,
Bardestani, A. ,
Ebrahimpour, S. ,
Esmaeili, A. BMC Pharmacology and Toxicology (20506511) 24(1)
Background: Quercetin (QC) possesses a variety of health-promoting effects in pure and in conjugation with nanoparticles. Since the mRNA-SIRT1/p66Shc pathway and microRNAs (miRNAs) are implicated in the oxidative process, we aimed to compare the effects of QC and QC-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on this pathway. Methods: Through the use of the chemical coprecipitation technique (CPT), SPIONs were synthesized, coated with dextran, and conjugated with quercetin. Adult male Wistar rats were given intraperitoneal injections of streptozotocin to look for signs of type 1 diabetes (T1D). The animals were randomized into five groups: the control group got deionized water (DI), free QC solution (25 mg/kg), SPIONs (25 mg/kg), and QCSPIONs (25 mg/kg), and all groups received repeat doses administered orally over 35 days. Real-time quantitative PCR was used to assess the levels of miR-34a, let-7a-p5, SIRT1, p66Shc, CASP3, and PARP1 expression in the hippocampus of diabetic rats. Results: In silico investigations identified p66Shc, CASP3, and PARP1 as targets of let-7a-5p and miR-34a as possible regulators of SIRT1 genes. The outcomes demonstrated that diabetes elevated miR-34a, p66Shc, CASP3, and PARP1 and downregulated let-7a-5p and SIRT1 expression. In contrast to the diabetic group, QCSPIONs boosted let-7a-5p expression levels and consequently lowered p66Shc, CASP3, and PARP1 expression levels. QCSPIONs also reduced miR-34a expression, which led to an upsurge in SIRT1 expression. Conclusion: Our results suggest that QCSPIONs can regulate the SIRT1/p66Shc-mediated signaling pathway and can be considered a promising candidate for ameliorating the complications of diabetes. © 2023, The Author(s).
Ebrahimpour, S. ,
Esmaeili, A. ,
Esmaeili, A. ,
Sattari, K. ,
Forouzandeh hafshejani, K. Oral Diseases (1354523X) 29(3)pp. 1356-1366
Objective: This study aimed to investigate the relationship between different patterns of molar crown loss and the association between symmetrical and asymmetrical shortening molar teeth with memory impairment. Materials and methods: Male Wistar rats were divided into four groups (n = 10) including control, SLM (shortened left molar), SRM (shortened right molar), and SBM (shortened bilateral molar) groups. Morris water maze (MWM) and passive avoidance test (PAT) were performed to assess spatial and fear memory, respectively. Besides, histological assessment of hippocampus and gingival tissues was done. Results: In the MWM test, SBM and SLM groups had higher escape latency over training trials and spent less time in the target quadrant in the probe trial (p < 0.01). In the PAT, step-through latency was significantly reduced in three groups, and time spent in the dark compartment increased in SBM (p < 0.01) and SLM (p < 0.05) groups. In addition, each teeth shortening group indicated a reduction in density (p < 0.01) and thickness layer (p < 0.05) of pyramidal cells. Gingival was normal after shortening of the molar crown. Conclusions: Different patterns of molar teeth shortening induced learning and memory impairment; however, symmetrical molar teeth shortening has more effects on memory impairment. © 2021 Wiley Periodicals LLC.
BioImpacts (22285652) 12(4)pp. 295-299
Despite the progress made in the diagnosis and treatment of cancer, it has remained the second cause of death in industrial countries. Cancer is a complex multifaceted disease with unique genomic and proteomic hallmarks. Optogenetics is a biological approach, in which the light-sensitive protein modules in combination with effector proteins that trigger reversibly fundamental cell functions without producing a long-term effect. The technology was first used to address some key issues in neurology. Later on, it was also used for other diseases such as cancer. In the case of cancer, there exist several signaling pathways with key proteins that are involved in the initiation and/or progression of cancer. Such aberrantly expressed proteins and the related signaling pathways need to be carefully investigated in terms of cancer diagnosis and treatment, which can be managed with optogenetic tools. Notably, optogenetics systems offer some advantages compared to the traditional methods, including spatial-temporal control of protein or gene expression, cost-effective and fewer off-target side effects, and reversibility potential. Such noticeable features make this technology a unique drug-free approach for diagnosis and treatment of cancer. It can be used to control tumor cells, which is a favorable technique to investigate the heterogeneous and complex features of cancerous cells. Remarkably, optogenetics approaches can provide us with outstanding tool to extend our understanding of how cells perceive, respond, and behave in meeting with complex signals, particularly in terms of cancer evasion from the anticancer immune system functions. © 2022 The Author(s).
Pharmaceutics (19994923) 14(12)
Regeneration of the damaged neurons in neurological disorders and returning their activities are two of the main purposes of neuromedicine. Combination use of specific nanoformulations with a therapeutic compound could be a good candidate for neuroregeneration applications. Accordingly, this research aims to utilize the combination of curcumin, as a neurogenesis agent, with dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate their effects on PC12 cellsʹ neuronal branching morphogenesis in the absence of nerve growth factor. Therefore, the effects of each component alone and in combination form on the cytotoxicity, neurogenesis, and neural branching morphogenesis were evaluated using MTT assay, immunofluorescence staining, and inverted microscopy, respectively. Results confirmed the effectiveness of the biocompatible iron oxide nanoparticles (with a size of about 100 nm) in improving the percentage of neural branching (p < 0.01) in PC12 cells. In addition, the combination use of these nanoparticles with curcumin could enhance the effect of curcumin on neurogenesis (p < 0.01). These results suggest that SPIONs in combination with curcumin could act as an inducing factor on PC12 neurogenesis in the absence of nerve growth factor and could offer a novel therapeutic approach to the treatment of neurodegenerative diseases. © 2022 by the authors.
Bhat, M.A. ,
Esmaeili, A. ,
Neumann, E. ,
Balakrishnan, K. ,
Benke, D. Frontiers in Pharmacology (16639812) 13
GABAB receptors control neuronal excitability via slow and prolonged inhibition in the central nervous system. One important function of GABAB receptors under physiological condition is to prevent neurons from shifting into an overexcitation state which can lead to excitotoxic death. However, under ischemic conditions, GABAB receptors are downregulated, fostering over-excitation and excitotoxicity. One mechanism downregulating GABAB receptors is mediated via the interaction with the endoplasmic reticulum (ER) stress-induced transcription factor CHOP. In this study, we investigated the hypothesis that preventing the interaction of CHOP with GABAB receptors after an ischemic insult restores normal expression of GABAB receptors and reduces neuronal death. For this, we designed an interfering peptide (R2-Pep) that restored the CHOP-induced downregulation of cell surface GABAB receptors in cultured cortical neurons subjected to oxygen and glucose deprivation (OGD). Administration of R2-Pep after OGD restored normal cell surface expression of GABAB receptors as well as GABAB receptor-mediated inhibition. As a result, R2-Pep reduced enhanced neuronal activity and inhibited progressive neuronal death in OGD stressed cultures. Thus, targeting diseases relevant protein-protein interactions might be a promising strategy for developing highly specific novel therapeutics. Copyright © 2022 Bhat, Esmaeili, Neumann, Balakrishnan and Benke.
BMC Research Notes (17560500) 14(1)
Objective: Papillary Thyroid carcinoma accounts for more than 60% of adult thyroid carcinomas. Finding a helpful marker is vital to determine the correct treatment approach. The present study was aimed to evaluate the expression of the B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) gene in papillary carcinoma, adenoma, and adjacent healthy thyroid tissues. Pathology blocks of thyroid tissues at the pathology department of patients who have undergone thyroid surgery between 2015 and 2019 were examined; papillary carcinoma, adenoma, and healthy tissues were selected and sectioned. Total RNA was extracted, and the relative expression level of the BMI-1 gene was examined using the Real-Time qPCR method. Results: In the papillary and adenoma tissues, BMI-1 was overexpressed (1.047-fold and 1.042-fold) in comparison to healthy tissues (p < 0.05 for both comparisons). However, no statistically significant differences were observed between adenoma and papillary carcinoma tissues regarding BMI-1 gene expression. This study demonstrated a new biomarker for thyroid malignancies and found that the mRNA levels of the BMI-1 gene were higher in tumor tissues compared with healthy tissues. Further studies are needed to evaluate the BMI1 gene expression in other thyroid cancers. © 2021, The Author(s).
Sinaei, M. ,
Alaei, H. ,
Nazem, F. ,
Kargarfard, M. ,
Feizi, A. ,
Talebi, A. ,
Esmaeili, A. ,
Nobari, H. ,
Pérez-gómez, J. Biochemical and Biophysical Research Communications (0006291X) 566pp. 204-210
Different exercise patterns, neurotransmitters, and some genes have numerous effects on learning and memory. This research aims to investigate the long-term effects of submaximal aerobic exercise on spatial memory (SM), passive avoidance learning (PAL), levels of serum relaxin-3, gamma-aminobutyric acid (GABA), RLN3 gene, and glutamic acid decarboxylase (GAD65/67 genes) in the brainstem of adult male Wistar rats. Fifty male Wistar rats were randomly divided into five groups: aerobic exercise groups, performed on a treadmill running (TR), for 5 weeks (Ex5, n = 10), 10 weeks (Ex10, n = 10), involuntary running wheel group for 5 weeks (IRW5, n = 10), sham (Sh, n = 10) and control (Co, n = 10). Consequently, SM, PAL, serum relaxin-3, GABA, and GAD65/67 and RLN3 genes were measured by ELISA and PCR. Ex5, Ex10 and IRW5 improved significantly SM (p ≤ 0.05), PAL (p ≤ 0.001) and decreased significantly relaxin-3 (p ≤ 0.001). RLN3 in the brain also decreased. However, it was not significant. GABA and GAD65/GAD67 increased significantly (p ≤ 0.05) in Ex5, Ex10 compared to Sh and Co. Aerobic exercise enhanced SM and PAL in Ex compared to Co and Sh. However, duration and type of exercise affected the level of enhancement. The serum relaxin-3 and RLN3 gene displayed reverse functions compared to GABA and GAD65/67 genes in Ex. Therefore, the changes of neurotransmitters in serum relaxin-3, GABA, and their genes: RLN3 and GAD65/67 respectively, influenced learning and memory meaningfully. © 2021 Elsevier Inc.
Archives of Oral Biology (00039969) 127
Objective: In the current study, we aimed to investigate the expression profile of TrkA, TrkB, TrkC, and p75NTR neurotrophin receptors because of their roles in the functional differentiation of human exfoliated deciduous teeth (SHED) cells into neural-like cells before and after differentiation of SHED cells into neural-like cells. Design: Total RNAs isolated from dental pulp tissue, SHED cells, and neural-like cells were reverse transcribed into complementary DNA. Neurotrophin receptor expression at mRNA and protein levels were compared in these three cell types by means of real-time PCR and western blot methods. Results: TrkA mRNA increased (713.6 ± 251.5) significantly (p < 0.01) in neural-like cells difference from SHED and TrkB mRNA enhanced to 3618 times in these cells. The expression pattern of TrkC was very similar to the pattern of TrkA, and B. p75NTR mRNA increased 41.99 ± 21.61 fold in neural-like cells and 9.805 ± 4.06 fold in SHED cells. Almost the same pattern was observed for the expression of these receptors at the protein levels. Alterations with different grades and trends in neurotrophin receptors mRNA and protein expression levels were observed in these cells. Conclusion: Neurotrophin receptors are important in the existence and differentiation of SHED cells into neuron cells. Therefore, because of the neurogenic potential and accessibility of SHED cells, derived cells from SHED cells can be distinguished as an ideal source for tissue engineering. © 2021 Elsevier Ltd
Bagheri, A. ,
Ebrahimpour, S. ,
Nourbakhsh, N. ,
Talebi, S. ,
Esmaeili, A. Archives of Oral Biology (00039969) 125
Objective: We aimed to assess the effect of quercetin as one of the most common polyphenols with anti-inflammatory and antioxidant properties on expression levels of catalase (CAT), superoxide dismutase 1 (SOD1), and glutathione peroxidase 1 (GPX1), involved in the detoxification of reactive oxygen species (ROS), and histology of dental pulp in streptozotocin-diabetic rats. Design: Type 1 diabetes mellitus (T1DM) was induced by intraperitoneal injection of streptozotocin in adult male Wistar rats. Animals (n = 24) were equally distributed into control, diabetes, and diabetes treated with quercetin groups. Rats were gavaged daily with quercetin (25 mg/kg) for forty days. To measure the mRNA levels of antioxidant genes, quantitate real-time PCR was applied. The oxidative stress parameters such as total antioxidant capacity (TAC) and histopathological assessments were performed. Results: A significant increase in the relative quantification mRNA levels of SOD1, CAT, GPX1 was detected in diabetic rat dental pulp. Besides, persistent hyperglycemia led to the enhancement of TAC level and degeneration of connective tissue of the dental pulp. Interestingly, quercetin normalized the expression mRNA levels of CAT, SOD1, GPX1 to near the normal level. Moreover, quercetin treatment normalized TAC levels. Conclusions: Because of the crucial role of antioxidants in diabetic complications, the findings of the current study presented a molecular basis for the protective effect of quercetin on dental pulp in diabetic conditions. © 2021 Elsevier Ltd
Journal of Nanobiotechnology (14773155) 19(1)
Iron oxide nanoparticles (IONPs) have been proposed as targeted carriers to deliver therapeutic molecules in the central nervous system (CNS). However, IONPs may damage neural tissue via free iron accumulation, protein aggregation, and oxidative stress. Neuroprotective effects of quercetin (QC) have been proven due to its antioxidant and anti-inflammatory properties. However, poor solubility and low bioavailability of QC have also led researchers to make various QC-involved nanoparticles to overcome these limitations. We wondered how high doses or prolonged treatment with quercetin conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) could improve cognitive dysfunction and promote neurogenesis without any toxicity. It can be explained that the QC inhibits protein aggregation and acts against iron overload via iron-chelating activity, iron homeostasis genes regulation, radical scavenging, and attenuation of Fenton/Haber–Weiss reaction. In this review, first, we present brain iron homeostasis, molecular mechanisms of iron overload that induced neurotoxicity, and the role of iron in dementia-associated diseases. Then by providing evidence of IONPs neurotoxicity, we discuss how QC neutralizes IONPs neurotoxicity, and finally, we make a brief comparison between QC and conventional iron chelators. In this review, we highlight that QC as supplementation and especially in conjugated form reduces iron oxide nanoparticles neurotoxicity in clinical application. [Figure not available: see fulltext.] © 2021, The Author(s).
Scientific Reports (20452322) 11(1)
Quercetin (QC) is a dietary bioflavonoid that can be conjugated with nanoparticles to facilitate its brain bioavailability. We previously showed that quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) reduced the level of blood glucose in diabetic rats. Glucose transporters (GLUTs), insulin-like growth factor-1 (IGF-1), and microRNA-29 (miR-29) play a critical role in brain glucose homeostasis. In the current study, we examined the effects of QCSPION on the expression of glucose metabolism-related genes, and the miR-29 family as a candidate regulator of glucose handling in the hippocampus of diabetic rats. Our in silico analyses introduce the miR-29 family as potential regulators of glucose transporters and IGF-1 genes. The expression level of the miR-29 family, IGF-1, GLUT1, GLUT2, GLUT3, and GLUT4 were measured by qPCR. Our results indicate that diabetes significantly results in upregulation of the miR-29 family and downregulation of the GLUT1, 2, 3, 4, and IGF-1 genes. Interestingly, QCSPIONs reduced miR-29 family expression and subsequently enhanced GLUT1, 2, 3, 4, and IGF-1expression. In conclusion, our findings suggest that QCSPION could regulate the expression of the miR-29 family, which in turn increases the expression of glucose transporters and IGF-1, thereby reducing diabetic complications. © 2021, The Author(s).
Iranian Journal Of Basic Medical Sciences (20083874) 23(7)pp. 886-893
Objective(s): Chemotherapies used to treat colon cancer might often fail due to the emergence of chemoresistance and side effects. Escherichia coli Nissle 1917 (EcN) is a beneficial probiotic, whose molecular mechanisms in the prevention of colon cancer are yet to be fully understood. The present study assessed the anti-cancer effects of EcN treatments in human colorectal cancer, HT-29 cell line, with the analysis of related mechanisms. Materials and Methods: The co-culture conditioned-media (CM) of EcN with adenocarcinoma HT-29 cells and heat-inactivated bacteria (HIB) were applied for the treatment of the HT-29 cells. To study the inhibition potential of CM and HIB on cancer cells, various cellular/molecular analyses were implemented, including DAPI-staining and DNA ladder assays, flow cytometry and Real-time quantitative PCR (qPCR), as well as Western blotting analyses. Results: Our results indicated that EcN could elicit apoptotic impacts on the colon cancer HT-29 cells by up-regulating PTEN and Bax and down-regulating AKT1 and Bcl-xL genes. Conclusion: Based on our findings, EcN is proposed as a useful supplemental probiotic treatment against colon cancer.
Alizadeh, S. ,
Esmaeili, A. ,
Barzegari, A. ,
Rafi, M.A. ,
Omidi, Y. Journal of Drug Targeting (1061186X) 28(7-8)pp. 700-713
Despite many endeavours for the development of new anticancer drugs, effective therapy of solid tumours remains a challenging issue. The current cancer chemotherapies may associate with two important limitations, including the lack/trivial specificity of treatment modalities towards diseased cells/tissues resulting in undesired side effects, and the emergence of drug-resistance mechanisms by tumour cells causing the failure of the treatment. Much attention, therefore, has currently been paid to develop smart and highly specific anticancer agents with maximal therapeutic impacts and minimal side effects. Among various strategies used to target cancer cells, bacteria-based cancer therapies (BCTs) have been validated as potential gene/drug delivery carriers, which can also be engineered to be used in diagnosis processes. They can be devised to selectively target the tumour microenvironment (TME), within which they may preferentially proliferate in the necrotic and anaerobic parts–often inaccessible to other therapeutics. BCTs are capable to sense and respond to the environmental signals, upon which they are considered as smart microrobots applicable in the controlled delivery of therapeutic agents to the TME. In this review, we aimed to provide comprehensive insights into the potentials of the bioengineered bacteria as smart and targeted bio-carriers and discuss their applications in cancer therapy. © 2020 Informa UK Limited, trading as Taylor & Francis Group.
Ageing Research Reviews (15681637) 62
Obesity and diabetes are the most common metabolic disorders, which are strongly related to Alzheimer's disease (AD) in aging. Diabetes and obesity can lead to the accumulation of amyloid plaques, neurofibrillary tangles (NFTs), and other symptoms of AD through several pathways, including insulin resistance, hyperglycemia, hyperinsulinemia, chronic inflammation, oxidative stress, adipokines dysregulation, and vascular impairment. Currently, the use of polyphenols has been expanded in animal models and in-vitro studies because of their comparatively negligible adverse effects. Among them, quercetin (QT) is one of the most abundant polyphenolic flavonoids, which is present in fruits and vegetables and displays many biological, health-promoting effects in a wide range of diseases. The low bioavailability and poor solubility of QT have also led researchers to make various QT-involved nanoparticles (NPs) to overcome these limitations. In this paper, we review significant molecular mechanisms induced by diabetes and obesity that increase AD pathogenesis. Then, we summarize in vitro, in vivo, and clinical evidence regarding the anti-Alzheimer, anti-diabetic and anti-obesity effects of QT. Finally, QT in pure and combination form using NPs has been suggested as a promising therapeutic agent for future studies. © 2020 Elsevier B.V.
BioImpacts (22285652) 10(3)pp. 187-193
Introduction: Colorectal cancer (CRC) is one of the main health burden worldwide, which can cause major economic and physiological problems along with relatively high rate of mortality. It is important to develop new methods for the localized delivery of recombinant protein therapeutics, in large part due to the failure of conventional therapies in most cases. Since E. coli Nissle 1917 (EcN) does not produce any virulence factors, here we used these bacteria with the light-activated promoter system to deliver therapeutic agents in the desired location and time. Methods: In this study, Staphylococcus aureus alpha hemolysin (SAH), after codon usage optimization, was cloned into blue light activating vector (pDawn) and transferred to EcN strain. Then, the functionality and cytotoxicity of secreted alpha hemolysin was evaluated in the SW480 colon cancer cell line by using different experiments, including blood agar test, flow cytometry analysis, and DAPI staining. Results: Our findings revealed that EcN can produce functional SAH under the blue light irradiation against SW480 cancer cells. Moreover, cytotoxicity assays confirmed the dose- and time-dependent toxicity of this payload (SAH) against SW480 cancer cells. Conclusion: Based on our results, EcN is proposed as an appropriate light-activated vehicle for delivery of anticancer agents to the target cancer cells/tissues. © 2020 The Author(s).
Scientific Reports (20452322) 10(1)
Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) have an ameliorative effect on diabetes-induced memory impairment. The current study aimed to compare the effect of quercetin (QC) and QCSPIONs on inflammation-related microRNAs and NF-κB signaling pathways in the hippocampus of diabetic rats. The expression levels of miR-146a, miR-9, NF-κB, and NF-κB-related downstream genes, including TNF-α, BACE1, AβPP, Bax, and Bcl-2 were measured using quantitative real-time PCR. To determine the NF-κB activity, immunohistochemical expression of NF-κB/p65 phosphorylation was employed. Computer simulated docking analysis also performed to find the QC target proteins involved in the NF-κB pathway. Results indicate that diabetes significantly upregulated the expression levels of miR-146a, miR-9, TNF-α, NF-κB, and subsequently AβPP, BACE1, and Bax. Expression analysis shows that QCSPIONs are more effective than pure QC in reducing the expression of miR-9. Interestingly, QCSPIONs reduce the pathological activity of NF-κB and subsequently normalize BACE1, AβPP, and the ratio of Bax/Bcl-2 expression better than pure QC. Comparative docking analyses also show the stronger binding affinity of QC to IKK and BACE1 proteins compared to specific inhibitors of each protein. In conclusion, our study suggests the potent efficacy of QCSPIONs as a promising drug delivery system in memory improvement through targeting the NF-κB pathway. © 2020, The Author(s).
Physiology And Pharmacology (24765236) 24(1)pp. 46-53
Introduction: Frankincense expands memory performance in different experimental models of learning. Nevertheless, the causal molecular mechanisms have not been well investigated. The expression levels of some of the synaptic proteins might probably change following the consumption of frankincense. The present study investigated the effect of maternal injection of frankincense during gestation and lactation periods on memory performance and the mRNA expression levels of syntaxin1A and synaptophysin in the hippocampus of the offspring rats. Methods: Adult female Wistar rats weighing 180-220g received two doses (50 or 100mg/kg) of the aqueous extract of frankincense by gavage during gestation and lactation periods for 45 consecutive days, except three days after labor. The control group received water. Spatial memory was assessed in the male offspring rats using the Morris water maze. Quantitative PCR was used to measure mRNAs expression levels of syntaxin1A and synaptophysin. Results: Frankincense improved spatial memory retrieval in the offspring rats. Data analysis by one-way ANOVA demonstrated that frankincense did not change the expression levels of the hippocampal syntaxin1A mRNA in the offspring rats. However, it significantly decreased the expression levels of the hippocampal synaptophysin mRNA. Conclusion: The results indicate that consumption of frankincense during both gestation and lactation periods has a beneficial impact on spatial memory performance, which is accompanied by the down-regulation of the hippocampal synaptophysin mRNA. Nevertheless, this down-regulation did not change the improving effect of frankincense in memory. © 2020, Iranian Society of Physiology and Pharmacology. All rights reserved.
Cancer Medicine (20457634) 9(10)pp. 3537-3550
Drug resistance is a fundamental clinical concern in pediatric acute lymphoblastic leukemia (pALL), and methotrexate (MTX) is an essential chemotherapy drug administered for the treatment. In the current study, the effect of iron in response to methotrexate and its underlying mechanisms were investigated in pALL cells. CCRF-CEM and Nalm6 cell lines were selected as T and B-ALL subtypes. Cells were pretreated with ferric ammonium citrate, exposed to the IC50 concentration of MTX and cell viability was assessed using MTT, colony formation, and flow cytometry assays. Iron-loaded cells were strongly resistant to MTX cytotoxicity. The inhibitory effect of N-acetyl cysteine to reverse the acquired MTX resistance was greater than that of the iron chelator, deferasirox, highlighting the importance of iron-mediated ROS in MTX resistance. Subsequently, the upregulation of BCL2, SOD2, NRF2, and MRP1 was confirmed using quantitative RT-PCR. Moreover, a positive correlation was demonstrated between the MRP1 expression levels and bone marrow iron storage in pALL patients. Further supporting our findings were the hematoxylin and eosin-stained histological sections showing that iron-treated nude mice xenografts demonstrated significantly more liver damage than those unexposed to iron. Overall, iron is introduced as a player with a novel role contributing to methotrexate resistance in pALL. Our findings suggest that the patients' bone marrow iron stores are necessary to be assessed during the chemotherapy, and transfusions should be carefully administrated. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Ebrahimpour, S. ,
Shahidi, S.B. ,
Abbasi, M. ,
Tavakoli, Z. ,
Esmaeili, A. Scientific Reports (20452322) 10(1)
Oxidative stress is one of the earliest defects involved in the development of diabetes-induced cognitive impairment. Nrf2 is the master regulator of the cellular antioxidant system can be regulated by some microRNAs. The study aimed to evaluate the effects of quercetin (QC) and quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on Nrf2-controlled antioxidant genes through the redox-sensitive miR-27a. Expression levels of miR-27a, Nrf2, SOD1, GPX1, and CAT were measured by quantitative real-time PCR. Moreover, the oxidative stress parameters including total antioxidant capacity (TAC) and histological alterations were investigated. The expression level of miR-27a was significantly up-regulated in diabetic rats. While expression levels of Nrf2, SOD1, GPX1, and CAT were significantly down-regulated under diabetic condition. Interestingly, QCSPIONs decreased expression level of miR-27a and subsequently enhanced the expression levels of Nrf2, SOD1, and CAT to the control level. No significant difference was observed in the expression level of GPX1. Besides, QC in pure and especially conjugated form was able to normalize TAC and regenerate pathological lesions in STZ-diabetic rats. Our result demonstrates that QCSPIONs as an effective combined therapy can decrease miR-27a expression, which in turn increases the Nrf2 expression and responsive antioxidant genes, resulting in improvement of memory dysfunction in diabetic rats. © 2020, The Author(s).
Frontiers in Neuroscience (1662453X) 14
Alzheimer’s disease (AD) is a neurodegenerative disease with cognitive impairment. Oxidative stress in neurons is considered as a reason for development of AD. Antioxidant agents such as quercetin slow down AD progression, but the usage of this flavonoid has limitations because of its low bioavailability. We hypothesized that quercetin-conjugated superparamagnetic iron oxide nanoparticles (QT-SPIONs) have a better neuroprotective effect on AD than free quercetin and regulates the antioxidant, apoptotic, and APP gene, and miRNA-101. In this study, male Wistar rats were subjected to AlCl3, AlCl3 + QT, AlCl3 + SPION, and AlCl3 + QT-SPION for 42 consecutive days. Behavioral tests and qPCR were used to evaluate the efficiency of treatments. Results of behavioral tests revealed that the intensity of cognitive impairment was decelerated at both the middle and end of the treatment period. The effect of QT-SPIONs on learning and memory deficits were closely similar to the control group. The increase in expression levels of APP gene and the decrease in mir101 led to the development of AD symptoms in rats treated with AlCl3 while these results were reversed in the AlCl3 + QT-SPIONs group. This group showed similar results with the control group. QT-SPION also decreased the expression levels of antioxidant enzymes along with increases in expression levels of anti-apoptotic genes. Accordingly, the antioxidant effect of QT-SPION inhibited progression of cognitive impairment via sustaining the balance of antioxidant enzymes in the hippocampus of AD model rats. © Copyright © 2021 Amanzadeh Jajin, Esmaeili, Rahgozar and Noorbakhshnia.
Reviews in the Neurosciences (21910200) 30(5)pp. 555-572
Quercetin is a polyphenolic flavonoid, which is frequently found in fruits and vegetables. The antioxidant potential of quercetin has been studied from subcellular compartments, that is, mitochondria to tissue levels in the brain. The neurodegeneration process initiates alongside aging of the neurons. It appears in different parts of the brain as Aβ plaques, neurofibrillary tangles, Lewy bodies, Pick bodies, and others, which leads to Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and other diseases. So far, no specific treatment has been identified for these diseases. Despite common treatments that help to prevent the development of disease, the condition of patients with progressive neurodegenerative diseases usually do not completely improve. Currently, the use of flavonoids, especially quercetin for the treatment of neurodegenerative diseases, has been expanded in animal models. It has also been used to treat animal models of neurodegenerative diseases. In addition, improvements in behavioral levels, as well as in cellular and molecular levels, decreased activity of antioxidant and apoptotic proteins, and increased levels of antiapoptotic proteins have been observed. Low bioavailability of quercetin has also led researchers to construct various quercetin-involved nanoparticles. The treatment of animal models of neurodegeneration using quercetin-involved nanoparticles has shown that improvements are observed in shorter periods and with use of lower concentrations. Indeed, intranasal administration of quercetin-involved nanoparticles, constructing superparamagnetic nanoparticles, and combinational treatment using nanoparticles such as quercetin and other drugs are suggested for future studies. © 2019 Walter de Gruyter GmbH, Berlin/Boston 2019.
Aliakbari, M. ,
Mohammadian, E. ,
Esmaeili, A. ,
Pahlevanneshan, Z. Toxicology in Vitro (08872333) 54pp. 114-122
Polyvinylpyrrolidone superparamagnetic iron oxide nanoparticles (PVP-SPIONs) have unique properties. Due to these characteristics, PVP-SPIONs have been used in several medical applications such as magnetic resonance imaging (MRI) contrast agent or drug delivery system. However, a more comprehensive understanding of the environmental safety of PVP-SPIONs is vital for consumption of these nanomaterials. In this study, we describe the effects of PVP-SPIONs on cell viability of the BT-474 human breast cancer cells. Cell viability of the BT-474 cells treated with PVP-SPIONs (10–800 μg/ml) was assessed by MTT assay. MRC-5 cell line was used as a control. Quantitative real-time PCR was performed to investigate the mRNA expression levels of apoptotic (caspase 3) and anti-apoptotic (BCL2) genes Confluent BT-474 monolayers exposed to PVP-SPIONs showed biphasic effects on cell proliferation. PVP-SPIONs at 10–100 μg /ml promote proliferation of BT-474 cells but not the MRC-5 cells. At higher dosage, PVP-SPIONs have toxicity on BT-474 cells. The results of real-time PCR was in line with MTT assay. The increase of cell proliferation at low PVP-SPIONs concentrations is different from what would be expected for these nanoparticles. Our results suggest that more attentions are needed to ensure the safer use of SPION in nanomedicine. © 2018 Elsevier Ltd
Amidfar, M. ,
Karami, Z. ,
Kheirabadi, G. ,
Afshar, H. ,
Esmaeili, A. Journal Of Research In Medical Sciences (17351995) 24(1)
Background: Involvement of the immune system is one of the issues raised in the pathophysiology of depression. BCL2 and BAX genes are related to immune system regulation. We investigated the BCL2 and BAX expression as a probable mechanism of immune system involvement in depression. Materials and Methods: This case.control study was conducted on 28 patients with major depression (case) and 28 nondepressed individuals (control) within the age range of 18.55 years in the Isfahan University of Medical Sciences. Clinical interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, were conducted to detect depression, and Beck fs Depression Inventory was used to measure the severity of depression in the individuals. In addition, a real-time polymerase chain reaction was employed to compare the level of Bax and Bcl-2 gene expression in peripheral blood lymphocytes. The multivariate covariance analysis was used to explore the correlation between BCL2 and BAX gene expression and to control the effect of duration and severity of depression. Results: The results showed that none of the variables including group membership, the duration of depression, and the severity of depression were not significantly correlated with the expression of BCL2 and BAX genes. Furthermore, there was no statistically significant relationship between the Bax and Bcl-2 genes expression in case and control groups (P > 0.05). Conclusion: Depression may have no impact on Bax and Bcl-2 gene expression in patients with major depression. Studies with larger sample size are recommended. © 2019 Wolters Kluwer Medknow Publications. All rights reserved.
Rezaei, N. ,
Talebi, F. ,
Ghorbani, S. ,
Rezaei, A. ,
Esmaeili, A. ,
Noorbakhsh, F. ,
Ganjalikhani-hakemi, M. Inflammation (03603997) 42(1)pp. 235-245
Dysregulation of microRNAs (miRNAs) has been linked to the progress of a number of autoimmune diseases including multiple sclerosis (MS), and its animal model, experimental autoimmune encephalomyelitis (EAE). IFN-γ-producing Th1 cells are major players in MS/EAE pathogenesis. It is known that differentiation of T cells towards the Th1 phenotype is influenced by various factors including miRNAs. The miR-92a shows substantial upregulation in MS; however, little is known about its role in the development of autoimmune and inflammatory responses. Herein, we investigated the role of miR-92a in the pathogenesis of MS, focusing on its potential effects on differentiation of Th1 cells. The expression levels of miR-92a were assessed in the spinal cord tissues and splenocytes from mice with EAE using real-time RT-PCR. Next, using transfection with miR-92a mimic sequences, the potential involvement of miR-92a in Th1 polarization was investigated by flow cytometric analysis. Moreover, the expression levels of miR-92a targets were explored in spinal cord tissues of EAE mice. miR-92a expression was enhanced in mouse spinal cord samples at the peak of EAE disease. Overexpression of miR-92a in splenocytes led to increased differentiation of Th1 cells compared with cells transfected with negative control sequences. Enhanced miR-92a expression was accompanied by reduced expression TSC1 or DUSP10, predicted miR-92a targets, in EAE spinal cords. Our data point to a potential role for miR-92a in neuroinflammatory responses in EAE. Our results indicate that miR-92a might affect Th1 differentiation, likely due to downregulation of TSC1 and DUSP10. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
Amanzadeh, E. ,
Esmaeili, A. ,
Abadi, R.E.N. ,
Kazemipour, N. ,
Pahlevanneshan, Z. ,
Beheshti, S. Scientific Reports (20452322) 9(1)
Biomedical application of quercetin (QT) as an effective flavonoid has limitations due to its low bioavailability. Superparamagnetic iron oxide nanoparticle (SPION) is a novel drug delivery system that enhances the bioavailability of quercetin. The effect of short time usage of quercetin on learning and memory function and its signaling pathways in the healthy rat is not well understood. The aim of this study was to investigate the effect of free quercetin and in conjugation with SPION on learning and memory in healthy rats and to find quercetin target proteins involved in learning and memory using Morris water maze (MWM) and computational methods respectively. Results of MWM show an improvement in learning and memory of rats treated with either quercetin or QT-SPION. Better learning and memory functions using QT-SPION reveal increased bioavailability of quercetin. Comparative molecular docking studies show the better binding affinity of quercetin to RSK2, MSK1, CytC, Cdc42, Apaf1, FADD, CRK proteins. Quercetin in comparison to specific inhibitors of each protein also demonstrates a better QT binding affinity. This suggests that quercetin binds to proteins leading to prevent neural cell apoptosis and improves learning and memory. Therefore, SPIONs could increase the bioavailability of quercetin and by this way improve learning and memory. © 2019, The Author(s).
International Journal Of Nanomedicine (11782013) 14pp. 2157-2169
Background: The investigation of agents promoting recovery of nerve regeneration following neurodegenerative diseases has been the most important issue in neuroscience. Nerve growth factor (NGF) and quercetin as potential flavonoids could possibly have therapeutic applications in the field of degenerative diseases such as Parkinson and Alzheimer. Materials and methods: The MTT assay was done at 24, 48, and 72 hours to examine the cytotoxicity of superparamagnetic iron oxide nanoparticles (SPIONs) and quercetin. We combined NGF and quercetin with different concentrations of SPIONs as novel compounds to study their effect on neuronal branching morphogenesis of PC12 cells. Results: Morphological analysis showed a significant growth (P<0.001) in neurite length when PC12 cells were incubated in quercetin solution. We found a significant neurite outgrowth promotion and an increase in the complexity of the neuronal branching trees after exposing PC12 cells to both quercetin and SPIONs. In addition, a higher level of β3-tubulin expression was observed in these cells when treated with both quercetin and SPIONs. Conclusion: Different photographic analyses indicated that iron oxide nanoparticles function as an important factor in order to improve the efficiency of NGF through improving cell viability, cell attachment, and neurite outgrowth in the shelter of quercetin as an accelerator of these phenomena. The use of the quercetin-SPION complex as a suitable method for improving NGF efficacy and activity opens a novel window for substantial neuronal repair therapeutics. © 2019 Katebi et al.
International Journal Of Nanomedicine (11782013) 14pp. 6813-6830
Background: We recently showed that quercetin-conjugated iron oxide nanoparticles (QNPs) promoted the bioavailability of quercetin (Qu) in the brain of rats and improved the learning and memory of diabetic rats. In this study, we characterized the modifications in the antitoxic effects of Qu after conjugation. Materials and methods: We conjugated Qu to dextran-coated iron oxide nanoparticles (DNPs) and characterized DNPs and QNPs using FTIR, XRD, DLS, Fe-SEM, and EDX analyzes. The antiradical properties of Qu, DNPs, and QNPs were compared by 2, 2-diphenyl- 1-picrylhydrazyl (DPPH) scavenging activity assay. Catalase-like activities of DNPs and QNPs were estimated using catalase activity assay kit, and the antitoxic effects of Qu and QNPs were evaluated with spectrophotometry, MTT assay, flow cytometry, and real-time q-PCR. Results: Qu had a stronger anti-radical activity than DNPs and its activity decreased after being conjugated to DNPs. The catalase-like activity of DNPs remained intact after conjugation. DNPs had less toxicity on PC12 cells viabilities as compared to free Qu, and the conjugation of Qu with DNPs attenuated its cytotoxicity. Furthermore, MTT assay results indicated 24 h pretreatment with Qu had more protective effects than QNPs against H2O2- induced cytotoxicity, while Qu and QNPs had the same effects for 48 and 72 h incubation. Although the total antioxidant capacity of Qu was attenuated after conjugation, the results of flow cytometry and real-time q-PCR confirmed that 24 h pretreatment with the low concentrations of Qu and QNPs had the similar antioxidant, anti-inflammatory, and antiapoptotic effects against the cytotoxicity of H2O2. Conclusion: Qu and QNPs showed the similar protective activities against H2O2-induced toxicity in PC12 cells. Given the fact that QNPs have magnetic properties, they may serve as suitable carriers to be used in neural research and treatment. © 2019 Yarjanli et al.
Dehghani i., ,
Mostajeran a., A. ,
Esmaeili, A. ,
Ghanadian, M. Applied Ecology and Environmental Research (15891623) 17(2)pp. 4883-4902
Dehydration causes loss of wheat (Triticum aestivum L.) yield. Inoculation of wheat with Azospirillum brasilense improves its tolerance to drought. Although up-regulation of DREB2 gene has increased drought tolerance of wheat, less information exists about DREB2 expression under inoculation with A. brasilense. In this study, the physiological responses of different pairs of six wheat cultivars with A. brasilense Sp7 and Sp245 strains were evaluated to drought and the tolerant (Roshan-Sp245), sensitive (Shahpasand-Sp7), moderately tolerant (Roshan-Sp7) and moderately sensitive pairs (Shahpasand-Sp245) were selected. Afterward, in the second experiment, DREB2 expression of the selected pairs was evaluated under inoculation and/or dehydration (ψ w = -90 MPa) at 0, 120 and 360 minutes. At 120 min, DREB2 expression was more in the tolerant and moderately tolerant pairs than others and also higher in inoculated and/or dehydration conditions. Root’s DREB2 was up-regulated almost 700-fold in the tolerant and moderately tolerant pairs under dehydration. In contrast, in the sensitive cv., DREB2 expression did not change due to dehydration or inoculation. This could be the effect of compatibility or homology of A. brasilense strains and wheat cultivars which affected DREB2 expression. Therefore, DREB2 expression had a significant effect on increased drought tolerance in tolerant and moderately tolerant pairs. © 2019, ALÖKI Kft., Budapest, Hungary.
Journal of Cellular Biochemistry (07302312) 120(2)pp. 1185-1192
Since the morphology of the rooster spermatozoa is different to other animal spermatozoa, the aim of the current study was to investigate the transfection efficiency and cytotoxicity of polyethyleneimine (PEI) coated magnetic iron oxide nanoparticles (MION) on these cells. Liposome/nucleic acid (NA) complexes and PEI-coated MION linked to the labeled oligonucleotides were used. Viability and percentage of exogenous nucleic acid uptake of spermatozoa were measured by flow cytometry analyses. The results showed a significant increase in exogenous nucleic acid uptake by rooster spermatozoa (P < 0.001) when treated with MION-NA complexes in comparison to liposome/NA. There were no significant differences between efficiency of lipid-based transfection agent and MION (P > 0.05) during short incubation period. MION with or without magnetic field, did not show significant cytotoxicity while the lipid-based transfection agent significantly decreased (P < 0.05) the viability of rooster spermatozoa. Results of this study showed that magnetofection and lipofection were both effective methods which increased exogenous nucleic acid uptake by rooster spermatozoa. However, the magnetofection method was more successful in maintaining the cell's survival than lipofection method. © 2018 Wiley Periodicals, Inc.
Journal of Neurosurgical Sciences (03905616) 62(2)pp. 146-152
BACKGROUND: Neurotrophins as polypeptide growth factors have important roles during nervous system development and are involved in neuronal differentiation and survival and spinal cord reorganization. Neurotrophins have been recognized as factors which are involved in the development of damaged axons and increase the axon growth ability and neuroplasticity. Spinal cord injury (SCI) is associated with numerous physiological damages, leading to neuron death, axon extended destruction healthy and intact neurons demyelination, inflammation, cell death and severe motor/sensory defects. The aim of this study was to investigate the alteration in messenger RNAneurotrophin 4 and tyrosine kinase receptors B expression levels following SCI. METHODS: In this research, to know expression level alterations of neurotrophin 4 mRNA and its receptor Trk-B at 6 hours and 1, 3, 7 and 10 days after SCI, we developed competitive RT-qPCR. mRNAwas extracted from T9 injury site (epicenter, rostral and caudal to the epicenter) and reversed to cDNA. RESULTS: The results showed that the expression of these genes changed after SCI. The NT4 mRNAexpression level in the rostral to the epicenter decreased after enhancement in the 1st 6 hours. At the epicenter and in the caudal to the epicenter, it decreased. mRNAexpression level of Trk-B decreased after an increase in the initial hours in all the areas. CONCLUSIONS: The present results showed that NT4 and Trk-B are expressed temporary and spatially following SCIand the adjustment of these neurotrophins rate in SCI may provide therapeutic benefits. © 2016 EDIZIO NI MINERVA MEDICA.
International Journal Of Nanomedicine (11782013) 13pp. 6311-6324
Background: Diabetes mellitus plays a causative role in cognitive decline. Newly, neuroprotective effects of flavonoids have been widely investigated in neurodegenerative diseases. Quercetin (QC) is a phyto-derived bioactive flavone with numerous beneficial activities. However, its limited permeability to cross the blood–brain barrier, low oral bioavailability, poor aqueous solubility, and rapid gastrointestinal digestion lead to the administration of high dose of QC in clinical application. Materials and methods: In order to overcome these limitations, we conjugated QC with superparamagnetic iron oxide nanoparticles (QCSPIONs) and supplemented streptozotocin-induced diabetic rats with it to improve diabetes-related memory impairment. In this regard, 40 rats were distributed into five groups with eight animals: control, diabetes, and diabetes treated with SPIONs, QC, and QCSPIONs. All treatments (at the dose of 25 mg/kg) were dissolved in deionized water and gavaged for 35 consecutive days. Results: At the end of the study, QCSPIONs possessed significantly better efficacy than free QC on the improvement of memory performance. In the Morris water maze test, QCSPIONs compared to free QC reduced much better the escape latency over training trials (P<0.01) and increased the time spent in the target quadrant in probe trial (P<0.001). In the passive avoidance test, it increased step-through latency (P<0.05) and reduced the time spent in the dark compartment (P<0.01). In addition, both free QC and QCSPIONs were able to prevent the changes in body weight and decrease blood glucose levels in diabetic rats (P<0.05). Conclusion: Overall, according to these results, we conclude that QC in the conjugated state with lower dose offers significantly higher potency in ameliorating diabetes-related memory impairment. Thus, this study offers an effective combined therapy for improving learning and memory. © 2018 Ebrahimpour et al.
Kazemipour, N. ,
Nazifi, S. ,
Poor, M.H.H. ,
Esmailnezhad, Z. ,
Najafabadi, R.E. ,
Esmaeili, A. Comparative Clinical Pathology (1618565X) 27(6)pp. 1621-1628
The pharmaceutical use of quercetin is limited due to the problems such as low solubility, bioavailability, permeability, and instability. High doses of quercetin show toxic effects in clinical and experimental studies. Therefore, a method is needed to overcome these problems without the use of toxic doses. Iron oxide nanoparticles can be used as a drug delivery system. Biocompatible polymers such as dextran are used to cover nanoparticles to increase the stability of nanoparticles. Besides their beneficial effects, nanoparticles can cause toxicity, oxidative stress, and cellular dysfunction. The aim of the present study was to investigate the hepatotoxicity and nephrotoxicity of dextran-coated iron oxide nanoparticles (IONPs) and quercetin conjugated with IONPs (QNPs). This study was conducted for 1 week in eight groups of Wistar male rats including control, sham, quercetin (at doses of 50 and 100 mg/kg), dextran-coated IONPs (at doses of 50 and 100 mg/kg), and QNPs (at doses of 50 and 100 mg/kg). Rats were euthanized, and their liver and kidney tissues were evaluated for the changes in oxidative stress indices and important biochemical enzyme activities. Hepatic and renal AST, ALT, ALP, GGT, and LDH activities were not significantly different between control group and other groups. Hepatic TAC and GSH levels and CAT activity significantly increased, and MDA level significantly decreased in rats injected with 100 mg/kg quercetin compared to the control group. IONPs of 100 mg/kg induced a significant decrease in hepatic GSH level and CAT activity and a significant increase in hepatic MDA. Hepatic TAC, GSH and MDA levels, and CAT activity were not significantly different between QNP groups and the control group. Renal CAT activity showed a significant increase in 100 mg/kg quercetin group and a significant decrease in 100 mg/kg IONP group compared to the control group. However, renal TAC, GSH, and MDA levels were not significantly different among groups. Dextran-coated IONPs of 100 mg/kg caused oxidative damage in the hepatic tissue, but QNPs did not cause hepatic and renal oxidative injury. © 2018, Springer-Verlag London Ltd., part of Springer Nature.
Acta Agriculturae Slovenica (15819175) 111(2)pp. 431-443
Salinity stress reduces plant growth via failure of physiological processes mainly due to the abundance of Na+ ion. Salt overly sensitive (SOS) signaling pathway is considered as an important component of Na+/K+ homeostasis system in plants, especially under saline condition. Moreover, it is reported that wheat-Azospirillum associated has resulted in an enhanced salinity tolerance. To evaluate involvement of Azospirillum species in regulation of SOS signaling pathway, inoculated and none-inoculated wheat seedlings with Azospirillum brasilense Sp7 were grown for five days. Then uniform seedlings were transferred into saline hydroponic media with and without 200 mM NaCl. The relative expression of TaSOS1 of root, sheath, and blade as well as Na+/K+ ratio was measured after 6, 24 and 48 hours since inoculated and non-inoculated seedling were transferred to NaCl media. Simultaneously Ca, Fe, proline content, root and shoot dry mass and soluble sugars were measured at 72 hour after application of NaCl. Result showed that salinity increased TaSOS1 gene expression, Na+, prolin and Na+/K+ ratio but Ca and Fe were decreased in root and shoot of wheat seedlings. Although A. brasilense Sp7 could improve salinity tolerance in wheat via reduction of Na uptake and upregulation of TaSOS1 expression, but do not have any effect in sodium distribution within plant parts. Therefore, salinity could increase TaSOS1 expression in the root, sheath and blade and A. brasilense Sp7 also could reduce the adverse effect of salinity via addition of over expression of TaSOS1. © 2018 University of Ljubljana. All Rights Reserved.
BMC Pharmacology and Toxicology (20506511) 19(1)
Background: Quercetin (QT) as a bioactive flavonoid has a potential therapeutic activity for numerous neuronal injuries and neurodegenerative diseases. However, the low absorption rate of QT, especially through the blood-brain barrier, restricts its bioactivity in the body. The current research took the advantage of superparamagnetic iron oxide nanoparticles (SPIONs) to enhance the bioavailability of quercetin. Methods: Quercetin conjugated with SPIONs was prepared by means of nanoprecipitation method and was characterized by X-ray diffractometer, scanning electron microscope, and Fourier transformed infrared spectrometer analyses. Wistar male rats were orally fed by gavage with QT and QT-SPION at 50 and 100 mg/kg daily doses for 7 days. Using high-performance liquid chromatography (HPLC) method, biodistribution of QT was evaluated in plasma and brain tissue. Results: The outcomes of this research revealed a higher concentration in the plasma and brain of the rats fed with QT-SPION in comparison to free QT. Conclusion: The results of this study confirm that SPION as a targeted drug delivery system enhances the bioavailability of quercetin in the brain about ten folds higher than free quercetin and could be used for the treatment of neurodegenerative disorders. © 2018 The Author(s).
RSC Advances (20462069) 7(86)pp. 54835-54843
The 10-23 deoxyribozyme is considered as sequence-specific "molecular scissors" for RNA molecules. Extensive investigations have been reported for this deoxyribozyme in vitro and in eukaryotic host cells. However, few investigations are reported in the literature on the activity of this deoxyribozyme inside bacterial cells. The available reports focus on the cleavage of target mRNAs that encode for proteins which are responsible for the viability of bacterial colonies. Hence, the growth of bacterial cells was blocked and the main readouts in such studies were colony counts or optical density at 600 nm. In the current study, blue-white screening was utilized as a novel readout for analysis of the activity of the 10-23 deoxyribozymes in viable bacterial cells. Two deoxyribozymes were designed to target the α-peptide fragment from β-galactosidase (lacZ) mRNA at two different positions, i.e. 5′ untranslated region and translated region. Control experiments were performed utilizing DNA oligos that lacked the catalytic core. The 3′-3 inverted thymidine modified deoxyribozymes were compared with unmodified ones to analyze the effect of such modification in prokaryotic cells. The activity of the designed deoxyribozymes caused a significant retardation in the formation of the blue-color in colonies with deoxyribozymes. Miller assay confirmed the blue-white screening results. This report showed a proof of concept for application of blue-white screening as a readout system for the activity of the 10-23 deoxyribozyme that is a model RNA-cleaving deoxyribozyme. The result of this report can promote future investigations on the activity of deoxyribozymes in prokaryotic cells. © 2017 The Royal Society of Chemistry.
BMC Neuroscience (14712202) 18(1)
Background: In the recent decade, iron oxide nanoparticles (IONPs) have been proposed for several applications in the central nervous system (CNS), including targeting amyloid beta (Aβ) in the arteries, inhibiting the microglial cells, delivering drugs, and increasing contrast in magnetic resonance imaging. Conversely, a notable number of studies have reported the role of iron in neurodegenerative diseases. Therefore, this study has reviewed the recent studies to determine whether IONPs iron can threaten the cellular viability same as iron. Results: Iron contributes in Fenton's reaction and produces reactive oxygen species (ROS). ROS cause to damage the macromolecules and organelles of the cell via oxidative stress. Iron accumulation and oxidative stress are able to aggregate some proteins, including Aβ and α-synuclein, which play a critical role in Alzheimer's and Parkinson's diseases, respectively. Iron accumulation, oxidative stress, and protein aggregation make a positive feedback loop, which can be toxic for the cell. The release of iron ions from IONPs may result in iron accumulation in the targeted tissue, and thus, activate the positive feedback loop. However, the levels of IONPs induced toxicity depend on the size, concentration, surface charge, and the type of coating and functional groups of IONPs. Conclusion: IONPs depending on their properties can lead to iron accumulation, oxidative stress and protein aggregation in the neural cells. Therefore, in order to apply IONPs in the CNS, the consideration of IONPs properties is crucial. © 2017 The Author(s).
Behavioural Brain Research (18727549) 320pp. 85-90
Gap junction channels are implicated in learning and memory process. However, their role on each of the particular stages of memory formation has been studied less. In this study, the time profile of the expression levels of hippocampal connexins 36 and 45 (Cx36 and Cx45) mRNAs was measured during memory consolidation, in a passive avoidance paradigm. Totally 30 adult male rats were distributed into 5 groups of each 6. At different times profiles (30 min, 3, 6 and 24 h) following training, rats were decapitated and their hippocampi were immediately removed and frozen in liquid nitrogen. Total RNA was extracted and cDNA was synthesized, using oligo-dt primers. A quantitative real-time PCR was used to measure the levels of each of Cx36 and Cx45 mRNAs. Both connexins showed a rapid upregulation (30 min) at the transcriptional level, which declined in later times and reached to the control level at 24 h. The rapid up-regulation of Cx36 and Cx45 mRNAs might be accompanied with increasing intercellular coupling via gap junction channels and neuronal oscillatory activities required for memory consolidation. The results highlight the role of gap junctional coupling between hippocampal neurons during memory consolidation in the physiological conditions. © 2016 Elsevier B.V.
Journal of Babol University of Medical Sciences (15614107) 18(6)pp. 66-72
BACKGROUND AND OBJECTIVE: Gamma-aminobutyric acid (GABA) is a four-carbon non-protein amino acid used in the treatment of hypertension, diabetes, inflammation, and depression. GABA is synthesized by glutamic acid decarboxylase (GAD) enzyme in many organisms, including bacteria. Therefore, cloning of this enzyme is essential to the optimization of GABA production. This study aimed to clone and construct the expression vector of GAD gene from Lactobacillus plantarum PTCC 1058 bacterium. METHODS: In this experimental study, we investigated the morphological, biochemical, genetic and 16s rDNA sequencing of L. plantarum PTCC 1058 strain. Genomic DNA of the bacterium was isolated and amplified using the GAD gene via polymerase chain reaction (PCR). Afterwards, the gene was inserted into the pJET1.2/blunt cloning vector and subcloned in vector pET32a. Plasmid pET32a-gad expression vector was transformed in Escherichia coli BL21 strain, and protein expression was assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). FINDINGS: Morphological, biochemical and genetic analyses of 16s rDNA sequencing indicated that the studied substrain was of the L. plantarum strain. In addition, results of nucleotide sequencing of the fragmented segment via PCR showed the presence of GAD gene. Results of colony PCR and SDS-PAGE analysis confirmed the accuracy of the cloning and gene expression of the recombinant Escherichia coli BL21 strain. CONCLUSION: According to the results of this study, cloning of GAD gene from L. plantarum PTCC 1058 was successful. These cloned genes could grow rapidly in prokaryotic and eukaryotic systems and be used in cost-effective culture media and even non-recyclable waste. © 2016, Babol University of Medical Sciences. All rights reserved.
Molecular And Cellular Biochemistry (03008177) 412(1-2)pp. 229-233
CCX-CKR (CCRL1) as one of the chemokine receptor-like proteins is a scavenger of CCL19, CCL21, CCL25, and CXCL13 chemokines. Human CCX-CKR is expressed in various tissues. Since HEK 293 cells are used for both transient and stable expression of CCX-CKR gene, it is important to determine endogenous expression of CCX-CKR gene. Therefore, in the current study endogenous expression of CCX-CKR gene was evaluated in HEK 293 cells. To test the expression of CCX-CKR gene in HEK 293 cells, total RNA was isolated from HEK 293 cells and RT-PCR reaction was primed with the gene-specific primers. Protein expression is then evaluated by Western blot analysis and flow cytometry. Results of this study show that HEK 293 cells express an endogenous CCRL1 gene only at mRNA level. These data therefore represent the important implications for the use of HEK 293 cells as a host cell system for the study of CCX-CKR. © 2015, Springer Science+Business Media New York.
Network Modeling Analysis in Health Informatics and Bioinformatics (21926670) 5(1)
An in silico study was conducted to identify antigens with potential possibility of being a vaccine against type 1 diabetes mellitus (T1DM). A molecular mimicry between protein 2C of coxsackievirus B4 and autoantigen glutamic acid decarboxylase 65 is a significant factor in the pathogenesis of T1DM. The aim of this study was to predict the protein 2C of coxsackievirus B4 epitopes and design a vaccine against T1DM. Several web servers were used to predict continuous B cell epitopes and 8 peptides (P1–P8) were selected. Then the 3D structure of P2C was built by structural modeling using Robetta and the structure was subjected to 10 ns molecular dynamics simulation by Amber to obtain an average structure in an explicit water system. Molecular mimicry theory was confirmed by local structural alignment of modeled structure protein 2C with glutamic acid decarboxylase 65 using Swiss pdb viewer. Then conformational B cell epitope web servers were used to identify discontinuous B cells epitopes. PDBsum was used for the analysis of the protein 2C secondary structure. Finally, T cells epitopes have been predicted by the immune epitope database analysis resource (IEDB). In silico analysis of the sequence and structure retrieved by mentioned methods and web servers, revealed that two out of 8 peptides (P2 and P7 epitopes) are the best choices for the vaccine design. These results suggest that epitopes and structural features of the protein 2C of coxsackievirus B4 can be predicted and this information could be used to make novel vaccines for control of T1DM. © 2016, Springer-Verlag Wien.
Computational Biology and Chemistry (14769271) 64pp. 74-81
Glutamate decarboxylase (GAD) is an enzyme that converts l-glutamate to gamma amino butyric acid (GABA) that is a widely used drug to treat mental disorders like Alzheimer's disease. In this study for the first time point mutation was performed virtually in the active site of the E. coli GAD in order to increase thermal stability and catalytic activity of the enzyme. Energy minimization and addition of water box were performed using GROMACS 5.4.6 package. PoPMuSiC 2.1 web server was used to predict potential spots for point mutation and Modeller software was used to perform point mutation on three dimensional model. Molegro virtual docker software was used for cavity detection and stimulated docking study. Results indicate that performing mutation separately at positions 164, 302, 304, 393, 396, 398 and 410 increase binding affinity to substrate. The enzyme is predicted to be more thermo- stable in all 7 mutants based on ΔΔG value. © 2016 Elsevier Ltd. All rights reserved.
Journal of Magnetism and Magnetic Materials (03048853) 402pp. 184-189
Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer. © 2015 Elsevier B.V.
Molecular Biology Reports (03014851) 43(7)pp. 583-589
ACKR4 also called CCX-CKR, CCRL1 as a member of atypical chemokine receptors, regulates the biological responses by clearance or transporting homeostatic chemokines such as CCL19, CCL21, CCL25, and CXCL13. Since these chemokines are involved in cancer development and metastasis, ACKR4 could have inhibition roles in cancer cell proliferation and invasion. Forming complexes with chemokine receptors by ACKR4 as in the case of hCXCR3 which lead to chemotaxis prevention is the other function of this protein is. However, as an atypical chemokine receptor, ACKR4 is less well-characterized compared to other members. Here, as the first step in understanding the molecular mechanisms of ACKR4 action, transfectants in HEK293T cell, was generated. In this study, ACKR4 coding sequence was cloned and human embryonic kidney 293T cells were used for recombinant production of ACKR4 protein. The liposome-mediated transfection with ACKR4 CDs, were detected in ACKR4 positive cells as early as 48 h post-transfection. The production of ACKR4 protein was confirmed using RT-PCR, dot blot, western blot, and flow cytometry. ACKR4 may represent a novel molecular target in cancer therapy, which might provide a chance for new therapeutic strategy. Therefore, the first step in the understanding of the molecular mechanisms of ACKR4 action is generation ACKR4-HEK293T recombinant cells. © 2016, Springer Science+Business Media Dordrecht.
Pharmacological Reports (17341140) 67(2)pp. 370-375
Background Neuroinflammation is considered to be a major factor in several neurodegenerative diseases. Recently, the polyunsaturated fatty acid omega-3 has been shown to have anti-inflammatory effects and might play an effective role in improving memory impairment due to inflammation. In order to test this, we stimulated neuroinflammation in an animal model and induced memory dysfunction as measured by reduced retention of passive avoidance learning (PAL) and altered expression of CaMKII-α, a gene known to be crucial for memory formation. We then investigated whether treatment with dietary omega-3 prevents inflammation-induced memory dysfunction in this model.
Nikbakht dastjerdi m., ,
Babazadeh z., ,
Rabbani, M. ,
Gharagozloo m., ,
Esmaeili, A. ,
Narimani m., M. Research in Pharmaceutical Sciences (17355362) 9(4)pp. 287-294
Pancreatic carcinoma is currently considered as a rapidly progressive and fatal disease, and is typically diagnosed late in its natural course. It is characterized by a poor diagnosis and lack of response to conventional therapy. Recent studies have suggested that disulfiram (DSF), a member of the dithiocarbamate family, may have antitumor activity. This study aimed to evaluate the in vitro effect of DSF on apoptosis in human pancreatic cancerous cell line (PANC-1). PANC-1 cells were cultured and treated with DSF at doses of 5, 10, 13 μM for 24 h and apoptosis was measured. Methylation specific PCR (MS-PCR) and real-time quantitative PCR were carried out to detect the methylation pattern and to estimate the mRNA expression levels of RASSF1A, p21 and Bax. MS-PCR analysis demonstrated that no unmethylated band was apeared in PANC-1 cell line after DSF treatments. The real-time quantitative PCR results showed no significant mRNA expression for RASSF1A (p>0.05); whereas p21 and Bax expression were significantly (p<0.01) enhanced after treatment with DSF. The results of the current study indicated that DSF can induce appoptosis in PANC-1 through p21 and Bax pathway but not through RASSF1A.
Journal of Babol University of Medical Sciences (15614107) 16(8)pp. 46-56
BACKGROUND AND OBJECTIVE: Gamma-aminobutyric acid (GABA) is a non-protein amino acid that can be found broadly in all organisms. GABA is synthesized by glutamate decarboxylase (GAD). Therefore, GABA production depends on biochemical properties of this enzyme. GABA has several physiological functions such as hypotensive activity, insomnia, depression, as well as diuretic effects. Bacteria, fungi and yeast produce considerable amount of GABA. Among bacteria, acid lactic bacteria due to their physiological and safety properties have been considered. These bacteria are used in food industry and act as probiotics in digestive system. The aim of this study was to identify and introduce GABA producing acid lactic bacteria. METHODS: In this paper using data banks such as PubMed and Google scholar and key words such as GABA producing acid lactic bacteria, isolation sources of them, factors that affect GABA production, acid lactic bacteria glutamate decarboxylase properties, glutamate decarboxylase gene cloning and regulation of them, the potential applications of GABA producing acid lactic bacteria and strain screenings have been reviewed. FINDINGS: Data from variety of papers showed that production of GABA using acid lactic bacteria is safe and biocompatible. This may lead to GABA rich fermented products. CONCLUSION: Results of this study showed that natural GABA has significant effects on human health. Therefore it seems acid lactic bacteria are the most suitable sources for GABA production. © 2014, Babol University of Medical Sciences. All rights reserved.
Genetics in the Third Millennium (24237159) 12(2)pp. 3564-3571
Nowadays, recombinant products have been produced using transgenic animal technology. So far, several techniques have been used to produce transgenic organisms. The most recent of these techniques is SMGT that has been established based on the ability of the sperm to uptake exogenous DNA and transfer it to the oocyte during fertilization. SMGT can be an efficient method when coupled with complementary methods such as electroporation, lipofection, ICSI, REMI and other techniques. The mechanism of the action of SMGT is not well defined. However, it seems that entering exogenous DNA into the sperm genome is a non-random event. The sperm chromatin condenses defines the limited sites for DNA integration. SMGT accompanied by other methods such as electroporation, lipofection, ICSI, REMI and other techniques can be an efficient method, but each of these methods has different efficiency and effects in different species. It is now clear that the sperm has the ability to transfer DNA molecules to egg during fertilization. Recent advances have reported that the efficiency of SMGT is growing and it is a cheap, fast and efficient technique for producing transgenic animals. © 2014, Iranian Neurogenetics Society. All rights reserved.
Avicenna Journal of Medical Biotechnology (20084625) 6(1)pp. 21-26
Background: Stem cells from Human Exfoliated Deciduous teeth (SHED) have the capability to differentiate into neural cells. Neurotrophins including Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), neurotrophin- 3 (NT-3), and neurotrophin-4 (NT-4) have neurogenesis, neurotrophic, or neuroprotective effects and are expressed in developing teeth. The aim of this study was to measure quantitative changes in mRNA expression levels of neurotrophins in neural-like cells differentiated from dental pulp stem cells. Methods: Isolated total RNA from SHED, dental pulp and neural-like cells (n=3) were transcribed into cDNA. Then real time PCR was done. Expression levels of mRNA for NGF, BDNF, NT-3, and NT-4 genes were compared in these three cells. Results: In neural like cells, BDNF mRNA increased (372.1±113.5) significantly (p<0.01) after differentiation. NGF mRNA increased to more than 266 times the dental pulp level after differentiation. A similar pattern was seen for the expression of NT3 after differentiation. NT4 mRNA enhancement was 1344± 630.8 and 30.7±7.9 fold in neural like cells and SHED cells, respectively. Results show alterations with different degrees and direction in neurotrophins mRNA expression levels in these cells. Conclusion: Our results suggest that neurotrophins dental pulp cells, SHED cells and neural like cells derived from SHED cells produce neurotrophic factors. Since the large amounts of neurotrophins are expressed in SHED and neural like cells they may have important role in survival and differentiation of dental pulp stem cells and obtained information may lead to a novel method for tooth regeneration. © 2014, Avicenna Journal of Medical Biotechnology. All rights reserved.
Rahgozar, S. ,
Moafi, A. ,
Abedi, M. ,
Entezar-e-ghaem, M. ,
Moshtaghian, J. ,
Ghaedi, K. ,
Esmaeili, A. ,
Montazeri, F. Cancer Biology and Therapy (15384047) 15(1)pp. 35-41
Multidrug resistance (MDR) is an important cause of treatment failure in acute lymphoblastic leukemia (ALL). The ABC family of membrane transporters is proposed, albeit with controversy, to be involved in this process. The present study aims to investigate the mRNA expression profile of several genes of this family, including ABCA 2, ABCA 3, ABCB1/MDR1, MRP1/ABCC 1, MRP3/ABCC 3, ABCG2/BCRP, and the intracellular transporter MVP/LRP, in childhood ALL, and to evaluate their association with response to therapy. Some genes in the present research are being studied for the first time in Iran. Using quantitative real time PCR, we evaluated 27 children with ALL at diagnosis and 15 children with normal bone marrow. The status of response to therapy was assessed one year after the onset of therapy through investigating the IgH/TCRγ gene rearrangements. Our findings indicate a considerable and direct relationship between mRNA expression levels of ABCA 2, ABCA 3, MDR1, and MRP1 genes and positive minimal residual disease (MRD) measured after one-year treatment. Statistical analysis revealed that expression of these genes higher than the cutoff point will raise the risk of MRD by 15-, 6.25-, 12-, and 9-fold, respectively. No relationship was found between of MVP/LRP, MRP3 and ABCG2 genes expression and ALL prognoses. Considering the direct and significant relationship between the increased expression of ABCA 2, ABCA 3, MDR1, and MRP1 genes and positive risk of MRD in children with ALL, evaluating the expression profile of these genes on diagnosis may identify high risk individuals and help plan a more efficient treatment strategy. © 2014 Landes Bioscience.
Esfandiari, E. ,
Karimipour, M. ,
Mardani, M. ,
Alaei, H. ,
Ghanadian, M. ,
Kazemi, M. ,
Mohammadnejad, D. ,
Hosseini, N. ,
Esmaeili, A. Journal of Neuroscience Research (10974547) 92(4)pp. 517-530
The number of older people who are suffering from memory impairment is increasing among populations throughout the world. Alzheimer's disease (AD) affects about 5% of people over 65 years old. The hippocampus, a brain area critical for learning and memory, is especially vulnerable to damage in the early stages of AD. Emerging evidence suggests that loss of neurons and synapses are correlated with dementia in this devastating disease. Therefore, neurogenesis and synaptogenesis in adulthood could serve as a preventive as well as a therapeutic target for AD. This study investigated the effect of Rosa damascena extract on neurogenesis and synaptogenesis in an animal model of AD. Molecular, cellular, and behavioral experiments revealed that this treatment could induce neurogenesis and synaptic plasticity and improve memory in AD. Our study suggests that R. damascena is a promising treatment for mild memory impairments and AD. © 2013 Wiley Periodicals, Inc.
Tousheh, M. ,
Miroliaei, M. ,
Asghar rastegari, A. ,
Ghaedi, K. ,
Esmaeili, A. ,
Matkowski, A. Computers in Biology and Medicine (00104825) 43(11)pp. 1732-1738
A computational study was carried out to identify the structural determinant controlling the affinity, specificity and binding strength of several saturated and unsaturated fatty acids with Oryza sativa (Indica group) nonspecific lipid transfer protein (nsLTP2). Association between the number, position and conformation of hydrophobic patches and lipid binding properties of the protein was evidenced by docking analysis. Binding affinity is influenced by the number of carbon atoms, location of double bonds and hydroxyl group in the acyl chain. The results may direct at developing applications in LTP-mediated transport and controlled release of low molecular weight drugs. © 2013 Elsevier Ltd.
Razavi, S. ,
Mardani, M. ,
Kazemi, M. ,
Esfandiari, E. ,
Narimani m., M. ,
Esmaeili, A. ,
Ahmadi, N. Cellular and Molecular Neurobiology (02724340) 33(2)pp. 283-289
The Schwann cells (SCs) may be obtain from nerve biopsies for autologous transplantation. However, it is difficult to obtain sufficient amount of SCs for clinical applications. Human adipose-derived stem cells (ADSCs) can be induced to differentiate into Schwann-like cells (S-like cells) and used for autologous transplantation. However, effect of leukemia inhibitory factor (LIF) on the myelinogenic ability of SC-like cells induced from human ADSC is not investigated yet. The aim of this study was to evaluate of the effect of exogenous LIF on myelinogenic potential of differentiated cells in vitro. ADSCs were harvested from human fat tissue and characterized using flow cytometry. Human ADSCs were treated for sphere formation and LIF was added to terminal differentiation medium. GFAP/S100β and MBP markers were used to confirm differentiation of human ADSCs, and myelinogenic ability of SC-like cells, respectively, using both immunostaining and real-time RT-PCR analysis. The analysis for GFAP+/S100β+ revealed that LIF can increase both differentiated cells rates and the percentage of myelinating SC-like cells (p < 0.05). Our data showed that SC-like cells induced from human ADSCs were able to generate myelin when exposed to LIF and these cells could be a potential source for the treatment of peripheral and central axonal injuries. © 2012 Springer Science+Business Media New York.
Journal of Spinal Cord Medicine (20457723) 36(3)pp. 231-236
Background: Induction of p75 neurotrophin receptor (p75NTR) could be one of the first steps that initiate apoptotic cascade after injury, or it may indicate regeneration responses undertaken by the injured system, possibly in collaboration with resident tropomyosin-receptor-kinase (Trk). Objective: To measure quantitative changes in messenger RNA (mRNA) expression levels of p75NTR, Trk A, and caspase-9 in rat's injured spinal cord (SCI). The reciprocal interaction between Trk and p75NTR signaling pathways can dictate cellular responses to neurotrophins. p75NTR can regulate Trk-dependent responses, but the role of Trk in regulating p75NTR-dependent signaling is not well documented. Design: Using real-time polymerase chain reaction, this study analyzed changes in the mRNA abundance of the mentioned genes at 6, 24, and 72 hours and 7 and 10 days after SCI in adult male rats. SCI was induced at T9 level by transsection. Results: Results show a complicated temporal and spatial pattern of alteration with different degrees and direction (up- or down-regulation) in p75NTR, Trk A, and caspase-9 mRNA expression levels after SCI. The greatest variation was seen in center regions following SCI. This study shows that alteration in p75NTR, Trk A, and caspase-9 expression starts as early as 6 hours after SCI. Alterations in p75NTR, Trk A, and caspase-9 expression within the spinal cord may play a key role in the apoptotic cell death. Conclusion: Results suggest that the role of p75NTR is to eliminate damaged cells by activating the apoptotic machinery, especially at the center of damage and during first week after injury. © The Academy of Spinal Cord Injury Professionals, Inc. 2013.
Mardani, M. ,
Kabiri, A. ,
Esfandiari, E. ,
Esmaeili, A. ,
Pourazar, A. ,
Ansar, M. ,
Hashemibeni, B. Iranian Journal of Basic Medical Sciences (20083874) 16(11)pp. 1163-1169
Objective(s): Platelet-rich plasma (PRP) has recently emerged as a promising strategy in regenerative medicine due to its multiple endogenous growth factors. Little is known about the role of PRP as a promoter in chondrogenesis of human adipose derived stem cells (hADSCs). The aim of this study was to determine whether PRP may be considered as a natural and easy achievable source of growth factors to promote the chondrogenic differentiation of hADSCs in Transwell culture. Materials and Methods: Biochemical, immunohistological and molecular assays were used to evaluate the effect of different concentrations (5%, 10%, and 15%) of PRP on chondrogenic differentiation of hADSCs in Transwell culture. Results: The cells in the presence of 10% PRP produced markedly higher amounts of GAG and DNA, in comparison to the control group. PRP also increased chondrogenic markers in these cells, such as sox-9, aggrecan and collagen type II. A high expression level of collagen type X as a hypertrophic marker was observed in cartilage produced by using either PRP or TGF-β1.Conclusion: Our findings indicate that autologous PRP at an optimum concentration had beneficial effects on differentiation of hADSCs in Transwell culture. Further, in vivo studies are necessary to fully define the clinical implications of PRP.
Torktaz, I. ,
Mohamadhashem, F. ,
Esmaeili, A. ,
Behjati, M. ,
Sharifzadeh, S. Bioimpacts (22285660) 3(3)pp. 141-144
Introduction: Metastasis is a crucial aspect of cancer. Macrophage stimulating protein (MSP) is a single chain protein and can be cleaved by serum proteases. MSP has several roles in metastasis. In this in silico study, MSP as a metastatic agent was considered as a drug target. Methods: Crystallographic structure of MSP was retrieved from protein data bank. To find a chemical inhibitor of MSP, a library of KEGG compounds was screened and 1000 shape complemented ligands were retrieved with FindSite algorithm. Molegro Virtual Docker (MVD) software was used for docking simulation of shape complemented ligands against MSP. Moldock score was used as scoring function for virtual screening and potential inhibitors with more negative binding energy were obtained. PLANS scoring function was used for revaluation of virtual screening data. Results: The top found chemical had binding affinity of -183.55 based on MolDock score and equal to -66.733 PLANTs score to MSP structure. Conclusion: Based on pharmacophore model of potential inhibitor, this study suggests that the chemical which was found in this research and its derivate can be used for subsequent laboratory studies. © 2013 by Tabriz University of Medical Sciences.
Kabiri, A. ,
Esfandiari, E. ,
Hashemibeni, B. ,
Kazemi, M. ,
Mardani, M. ,
Esmaeili, A. Biochemical and Biophysical Research Communications (0006291X) 424(2)pp. 234-238
Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10. ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering. © 2012 Elsevier Inc.
Nikbakht n., ,
Zarei b., ,
Shirani, E. ,
Moshtaghian, J. ,
Esmaeili, A. ,
Habibian s., Neuroscience (18737544) 218pp. 49-55
The expression of Arc and Homer 1a (H1a) depends on neural activity. This study was designed to determine hippocampal Arc and H1a mRNA expression levels after spatial learning with differing behavioral task demands. Forty-four male rats were distributed into 11 groups of four. One group received no training or trial sessions. Of the ten remaining groups, three were tested on the 8-arm maze, three on the 12-arm maze, two on the 8-arm maze and then the 12-arm maze, and two on the 12-arm maze and then the 8-arm maze. Each animal was sacrificed 30. min after the last session of maze testing and its hippocampus was immediately dissected and stored at -80°C. The level of mRNA expression at different stages of maze learning was determined using real-time reverse-transcription polymerase chain reaction (qRT-PCR). Significantly elevated expression of both Arc and H1a was observed. The orchestrated expression levels of both genes were correlated with the behavioral task demand level and behavioral performance. © 2012 IBRO.
Molecular Biology Reports (03014851) 39(3)pp. 2169-2178
VIGS (virus induced gene silencing) is considered as a powerful genomics tool for characterizing the function of genes in a few closely related plant species. The investigations have been carried out mainly in order to test if a pre-existing VIGS vector can serve as an efficient tool for gene silencing in a diverse array of plant species. Another route of investigation has been the constructing of new viral vectors to act in their hosts. Our approach was the creation of a heterologous system in which silencing of endogenous genes was achieved by sequences isolated from evolutionary remote species. In this study, we showed that a TRV-based vector cloned with sequences from a gymnosperm, Taxus baccata L. silenced the endogenous phytoene desaturase in an angiosperm, N. benthamiana. Our results showed that inserts of between 390 and 724 bp isolated from a conserved fragment of the Taxus PDS led to silencing of its homolog in tobacco. The real time analysis indicated that the expression of PDS was reduced 2.1- to 4.0-fold in pTRV-TbPDS infected plants compared with buffer treated plants. Once the best insert is identified and the conditions are optimized for heterologous silencing by pTRV-TbPDS in tobacco, then we can test if TRV can serve as an efficient silencing vector in Taxus. This strategy could also be used to silence a diverse array of genes from a wide range of species which have no VIGS protocol. The results also showed that plants silenced heterologously by the VIGS system a minimally affected with respect to plant growth which may be ideal for studying the genes that their complete loss of function may lead to decrease of plant growth or plant death. © Springer Science+Business Media B.V. 2011.
Iranian Journal Of Basic Medical Sciences (20083874) 15(5)pp. 1097-1101
Objective(s) In this study we investigated the expression of GABAA receptor subunits during brain development. These receptors may change in the embryonic chick forebrain. Materials and Methodes The expression levels of four types of GABAA receptor gamma subunits (γ1, γ2, γ3 and γ4) were quantified in the embryonic chick forebrain at 32 hr, 3, 7, 14, and 20 days of incubation and day one after hatching. The expression level of mRNA in the forebrain of embryonic chicken was measured using real-time RT-PCR. Results The expression level of each subunit increased gradually with development and reached a plateau on 20th day of embryonic development. A reduction was observed on day one after hatching in all gamma subunits. Conclusion This may explain the different physiological and pharmacological function of GABA receptor gamma subunits before and after hatching.
Ghoochani, A. ,
Shabani, K. ,
Peymani, M. ,
Ghaedi, K. ,
Karamali, F. ,
Karbalaei k.h., K. ,
Tanhaie, S. ,
Salamian, A. ,
Esmaeili, A. ,
Valian-borujeni, S. Differentiation (14320436) 83(1)pp. 60-67
Peroxisome proliferator activated receptor γ, belongs to PPARs, which exerts various metabolic functions including differentiation process. To testify the importance of PPARγ in neural differentiation of mouse embryonic stem cells (mESCs), its expression level was assessed. Data revealed an elevation in expression level of PPARγ when neural precursors (NPs) are formed upon retinoic acid treatment. Thus, involvement of PPARγ in two stages of neural differentiation of mESCs, during and post-NPs formation was examined by application of its agonist and antagonist. Our results indicated that PPARγ inactivation via treatment with GW9662 during NPs formation, reduced expression of neural precursor and neural (neuronal and astrocytes) markers. However, PPARγ inactivation by antagonist treatment post-NPs formation stage only decreased the expression of mature astrocyte marker (Gfap) suggesting that inactivation of PPARγ by antagonist decreased astrocyte differentiation. Here, we have demonstrated the stage dependent role of PPARγ modulation on neural differentiation of mESCs by retinoic acid treatment for the first time. © 2011 International Society of Differentiation.
Zahednasab h., H. ,
Saadatnia, M. ,
Jabalameli, M.R. ,
Zarkesh-esfahani, H. ,
Esmaeili, A. ,
Bahreini s.a., S.A. Journal of Neuroimmunology (01655728) 230(1-2)pp. 191-191
Spinal Cord (14765624) 49(2)pp. 280-284
Study design:Spinal cord injury (SCI) results in alterations in the regulation of many genes that may influence neuronal death and the subsequent loss of motor function and neuropathic pain. The subtype expression mRNA levels of glycine receptors (GlyRs) after SCI are unknown.Methods:Using real-time reverse transcription PCR, this study analyzed changes in the mRNA abundance of the four major GlyR subunits (α13 and β) at 6, 24 h and 3, 7 and 10 days after SCI in adult male rats. SCI was induced at the T9 level by transection.Results:Our results show a complicated temporal and spatial pattern of alteration in GlyR mRNA expression levels after SCI. Temporal and spatial variations with different degrees and direction (up or downregulation) of expression alteration were observed. The greatest variation was seen in GlyRα1, whereas GlyRα2 was downregulated in all regions following SCI.Conclusion:This study shows that alteration in GlyR expression starts as early as 6 h after SCI. The most significant points of this research are temporal elevation of GlyRα1 and continuous reduction of GlyRα2. Alterations in GlyR expression within the spinal cord may have a key role in the development of pathological pain. Therefore, control of GlyR expression could represent a novel therapeutic avenue for the development of new painkiller agents in SCI. © 2011 International Spinal Cord Society All rights reserved.
Journal of Diabetes and its Complications (10568727) 25(1)pp. 39-43
Background: Postsurgical adhesion formation is a significant clinical problem within every surgical specialty. In type I diabetic patients, the problem is more severe and wound healing is slow. A wide variety of treatments have been proposed to deal with the problems that adhesion causes. One of the modalities that have not been studied extensively yet is the use of amniotic fluid. The purpose of the present study was to evaluate the clinical value of bovine amniotic fluid (BAF) efficacy in the treatment of postsurgical adhesion formation in diabetic male rats. Materials and Methods: Fifty male Wistar rats in five groups were used for our study, with animal identification being facilitated by a microchip implant system. Diabetes was induced in all groups except for the control group by intraperitoneal alloxan injection (120 mg/kg). Based upon blood glucose concentration, rats received either one third of the required insulin (two groups) or all the required insulin (remaining groups). After 2 weeks, a laparotomy was performed on each rat and adhesions were scaled. Bovine amniotic fluid was then applied to two groups, and, as a control, sterilized water was applied to the other groups. After 2 weeks, a laparotomy was again performed on each rat and adhesion was rescored. Results and Conclusion: Significant reductions (P<.05) in adhesions were seen with BAF only in those diabetic rats that had received the required insulin. The results of our study suggest that BAF could be effective in the treatment of adhesion formation during diabetes. © 2011 Elsevier Inc. All rights reserved.
Shafaei h., ,
Esmaeili, A. ,
Mardani, M. ,
Razavi, S. ,
Hashemibeni, B. ,
Nasr-esfahani, M.H. ,
Shiran m.b., ,
Esfandiari, E. Bone Marrow Transplantation (14765365) 46(11)pp. 1464-1471
Media used for tissue culture may have significant effects on the growth and morphology of the adipose tissue-derived stem cells (ADSCs). As fetal bovine serum (FBS) may induce an immunological reaction and health risks, this study was designed to evaluate and compare the effects of human placental serum (HPS) on the proliferation and morphology of hADSCs. We cultured hADSCs for at least three passages in four different culture media containing either FBS, HPS, autologous serum (AS) or human allogeneic serum (HAS). Morphological and immunophenotypic characteristics, as well as proliferation rates of the hADSCs were determined. The rates of proliferation of hADSCs seemed as follows: AS>HPS≫HAS≥FBS. Morphologically, hADSCs isolated and expanded in medium containing HPS were similar to those grown in medium containing AS, whereas the morphology of cells cultured in human sera was different in comparison with FBS-ADSCs cultures. The immunophenotypic markers of hADSCs grown up in medium containin actal serum such as CD44 +, CD90 + and CD105 +, were similar to hADSCs grown up in media containing other sera. These results indicate that medium enriched with HPS provided a better microenvironment for hADSCs in comparison with medium enriched with commercially available FBS, and other human sera. © 2011 Macmillan Publishers Limited All rights reserved.
European Journal of Neurology (14681331) 18(8)
Journal of Theoretical Biology (10958541) 281(1)pp. 18-23
The amino acid gamma-aminobutyric-acid receptors (GABAARs) belong to the ligand-gated ion channels (LGICs) superfamily. GABAARs are highly diverse in the central nervous system. These channels play a key role in regulating behavior. As a result, the prediction of GABAARs from the amino acid sequence would be helpful for research on these receptors. We have developed a method to predict these proteins using the features obtained from Chou's pseudo-amino acid composition concept and support vector machine as a powerful machine learning approach. The predictor efficiency was assessed by five-fold cross-validation. This method achieved an overall accuracy and Matthew's correlation coefficient (MCC) of 94.12% and 0.88, respectively. Furthermore, to evaluate the effect and power of each feature, the minimum Redundancy and Maximum Relevance (mRMR) feature selection method was implemented. An interesting finding in this study is the presence of all six characters (hydrophobicity, hydrophilicity, side chain mass, pK1, pK2 and pI) or combination of the characters among the 5 higher ranked features (pk2 and pI, hydrophobicity and mass, pk1, hydrophilicity and mass) obtained from the mRMR feature selection method. The results show a biologically justifiable ranked attributes of pk2 and pI; hydrophobicity, hydrophilicity and mass; mass and pk1; pk2 and mass. Based on our results, using the concept of Chou's pseudo-amino acid composition and support vector machine is an effective approach for the prediction of GABAARs. © 2011.
Hepatitis Monthly (1735143X) 11(2)pp. 130-131
Esmaeili, A. ,
Akhavan a., A. ,
Bouzari, M. ,
Mousavi s.b., ,
Torabinia n., ,
Adibi s., S. International Endodontic Journal (13652591) 44(6)pp. 499-504
Aim To determine mRNA expression levels of Nav 1.8 in inflamed pulps of rats. Methodology Inflammation was induced by creating pulp exposures in rat incisors. Histopathological changes in the induced pulpitis were evaluated 1, 3, 7 and 10days after exposure. Using real-time PCR, the relative mRNA expression levels of Nav 1.8 in the inflamed rat dental pulp was determined. Results At day 1, no inflammation was evident in the pulp tissue, whereas increased levels of inflammatory responses were identified at day 3 and day 7. No pulpal inflammation was evident in day 10 or in the control group. Nav 1.8 was expressed in the rat dental pulp and increased at day 3 and day 7. Time course study of dental pulp inflammation indicated that differences in relative mRNA expression levels of Nav 1.8 were correlated with the severity of inflammation. Conclusions Nav 1.8 channels seem to be expressed significantly more under a temporal control so as to be associated with a severity of inflammation during pulpitis. As Nav 1.8 has been considered to have a role in neuropathic pain, its expression within dental pulp may contribute to the pathophysiology of tooth pain. © 2011 International Endodontic Journal.
Russian Journal of Plant Physiology (10214437) 57(4)pp. 480-484
Expression of two key biosynthetic enzymes for terpenoid biosynthesis (squalene synthase and beta-amyrin synthase) was analyzed in licorice as a model organism. For two elicitors, methyl jasmonate (MeJa) and salicylic acid (SA), the roots of 65-day-old plantlets treated with a combination of various elicitor concentrations and treatment times were used for RNA extraction and reverse transcription to cDNA. A protocol for real-time quantitative PCR (RT-qPCR) analysis of these two genes was developed (relative approach) using 18S rRNA gene as an internal standard. Results showed that after 24 h of elicitation, transcripts of SQS gene were increased at all concentrations of the MeJa, but increased only at 0.1 and 1 mM of SA. For bAS gene, after 24 h of elicitation, transcripts were increased at 0.1, 1, and 2 mM of MeJa, while they were increased only at 0.1 and 1 mM SA. These results are discussed and showed that they are well in accordance with our previous results on glycyrrhizin accumulation in the roots. © 2010 Pleiades Publishing, Ltd.
Delaney a.j., ,
Esmaeili, A. ,
Sedlak p.l., ,
Lynch j.w., J.W. ,
Sah p., P. Neuroscience Letters (03043940) 469(2)pp. 237-242
The amygdalar complex is a limbic structure that plays a key role in emotional processing and fear conditioning. Although inhibitory transmission in the amygdala is predominately GABA-ergic, neurons of the amygdala are also known to express glycine receptors. The subtype and function of these glycine receptors within the synaptic circuits of the amygdala are unknown. In this study, we have investigated the relative expression of the four major glycine receptor subunits (α1-3 and β) in the rat basolateral (BLA) and central amygdala (CeA), using real-time PCR and protein biochemistry. We demonstrate that α1, α2, α3, and β subunits are all expressed in the BLA and CeA with α2 being the predominant α-subunit in both nuclei. Electrophysiological recordings from BLA and CeA neurons in acute brain slices indicated that differences in relative expression of these subunits were correlated with the pharmacological properties of native glycine receptors expressed on these neurons. We conclude that glycine receptors assembled in BLA neurons are largely α1β-containing heteromultimers whereas receptors assembled in neurons of the central amygdala are primarily α2β-, α3β- or α1β-containing heteromultimers, with a minor component of α2 or α3 homomeric receptors also expressed. © 2009 Elsevier Ireland Ltd. All rights reserved.
International Journal of Surgery (17439191) 8(8)pp. 639-642
Background: A wide variety of treatments have been proposed in order to deal with prevention of postoperative adhesions formation, but, no definitive results have been achieved. In the present study, bovine amniotic fluid (BAF) has been investigated as a possible option. Materials and methods: 84 male Wistar rats were undergone a laparotomy. After 2 weeks, adhesions were scaled grossly. Bovine amniotic fluid (in whole combination, without cells or without cells and proteins) extracted from cows carried either male or female calves was then applied to treated groups 2 weeks later during the second laparotomy. Adhesions were rescored 2 weeks later during a third laparotomy. Results and conclusion: A significant reduction (P< 0.05) in adhesions formation was observed only in rats treated with male bovine amniotic fluid without cells and proteins. Therefore, BAF could be used in treatment of adhesion formation because it is inexpensive, readily available, and has minimal side effects. © 2010 Surgical Associates Ltd.
Ghasemi, S. ,
Ghaedi, K. ,
Esfahani, M.N. ,
Tanhaei, S. ,
Rabeei, F. ,
Karbalaii, K. ,
Baharvand, H. ,
Esmaeili, A. Yakhteh (15614921) 12(1)pp. 97
Objective: The aim of this study was to clone PPARγ1 cDNA in an appropriate mammalian expression vector, with a chimeric cDNA form, encompassing PPARγ with enhanced green fluorescent protein (EGFP) cDNA. This recombinant plasmid will be used for further analyses to investigate the molecular mechanism of PPARγ1 for neural differentiation process. Moreover, the nuclear localization of the PPARγ1 protein linked to EGFP marker was chased by using transient transfection of a constructed plasmid into bovine fibroblast cells. Materials and Methods: Total RNA was extracted from the fatty tissue of an adult mouse. Using specific pair primers, PPARγ1 cDNA was synthesized and amplified to produce the entire length of ORF. RT-PCR products containing PPARγ1 cDNA were treated by enzymatic digestion and inserted into the pEGFP-C1 downstream from EGFP cDNA. The constructed vector was used for transformation into bacterial competent cells. Positive colonies which showed inserted PPARγ1 cDNA were selected for plasmid preparations and additional analysis was performed to ensure that PPARγ1 cDNA was inserted properly. Finally, to confirm the intracellular localization of EGFP-PPARγ1, bovine fibroblast cells were transfected with the recombinant plasmid. Results: Our results from enzymatic digestion and sequencing confirmed, as expected, that PPARγ1 cDNA was amplified and cloned correctly. This cDNA gene encompassed 1428 bp. The related product was entered into the nucleus of bovine fibroblasts after transfection of its cDNA. Conclusion: PPARγ1 cDNA was cloned and sorted into nuclear compartments of bovine fibroblast cells upon transfection.
Journal of Neurophysiology (15221598) 101(1)pp. 341-349
γ-Aminobutyric acid (GABA) is the primary inhibitory transmitter in the mammalian brain. This inhibition is mediated by type A (GABAA) receptors that are pentameric proteins assembled from 14 different subunits. Although inhibitory synaptic transmission has been studied in the amygdala, the subunit composition of receptors present at different synapses is not well understood. In this study we examined the subunit composition of GABA A receptors at synapses in the basolateral and central amygdala. Using receptors expressed in HEK293 cells we first determined the pharmacology of receptors of different subunit compositions. We then used this pharmacological profile to test the properties of receptors present at synapses in the central and basolateral amygdala. These results show that the GABA A receptor subunits are differentially distributed in the amygdala. Our data indicate that in the basolateral amygdala, GABAergic synapses are likely composed of receptors that contain α2βxγ2 subunits. In the central amygdala receptors at the medial input, carrying afferents from the bed nucleus of the stria terminalis contain similar receptors, whereas in the lateral input GABA receptors likely contain γ1 subunits. These inputs arise from the intercalated cells masses, thought to be responsible for mediating extinction of conditioned fear, raising the possibility of new targets for the treatment of anxiety-related disorders. Copyright © 2009 The American Physiological Society.
Journal of Biomolecular Screening (1552454X) 14(1)pp. 86-91
Despite being important clinical targets, it is not straightforward to reliably express recombinant trimeric αβγ GABA-A receptors (GABAARs) for high-throughput screening. This study therefore sought to devise a simple and reliable means of transiently expressing α1β1γ1 and α1β1γ2 GABAARs in HEK293 cells. Expression efficiencies resulting from 5 different transfection strategies were assessed by flow cytometry and pharmacological analysis using an anion-sensitive yellow fluorescent protein-based assay. PolyFect™ and Effectene™, employed according to the manufacturers' instructions, conferred the strongest and most reliable expression of trimeric αβγGABAARs. Functional analysis via the yellow fluorescent protein assay revealed dramatic differences in the pharmacological properties of γ1- and γ2-containing receptors, consistent with previous electrophysiological characterizations. The authors conclude that this method of expressing and screening recombinant GABAARs provides an effective means of discovering novel GABAAR modulators for use as therapeutic lead compounds and pharmacological probes. © 2009 Society for Biomolecular Sciences.
International Journal of Fertility and Sterility (2008076X) 2(3)pp. 121-124
Background: γ-Aminobutyric acid (GABA) is considered to be the predominant inhibitory neurotransmitter in mammalian central nervous systems (CNS). There are two major classes of GABA receptors: GABAARs and GABABRs. The GABAA receptor is derived from various subunits such as alpha1-alpha 6, beta1-beta 3, gamma1-gamma 4, delta, epsilon, pi, and rho1-3. Intensive research has been performed to understand and establish the distribution and functions of these receptors in the CNS and peripheral tissues. The presence of some GABAA receptors in sperm prompted us to explore the existence of GABAA receptors in rat testis and sperm. Materials and Methods: Total cellular RNA was isolated from Wistar rat sperm and testis and reverse transcriptased to cDNA. PCR reactions were performed in a 20μl (microliter) volume containing specific GABAAR subunits (forward and reverse primers) with other required materials. Reactions were carried out using a PCR machine to investigate the existence of GABAA receptor subunits in rat testis and sperm. The amplification products were analyzed on 2% agarose gels stained with ethidium bromide. Results: Our results showed that GABAARs composed of α5, β1, β3, and γ1 subunits were expressed in both testis and sperm. These results indicate that, in sperm, GABAA receptors might have important functions. Conclusion: Sperm could be a novel site of GABAA expression. Further studies should be taken to explore the role of these receptors on sperm acrosome reaction.
