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1.
Noncoding RNA Res ; 7(1): 1-6, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35087989

ABSTRACT

In the current study, the effects of 7-BIO as a specific GSK3ß inhibitor was examined on cell survival and expression of miR-29a-3p and miR-34a-5p in neurotoxin MPP+ treated SH-SY5Y cells. Our findings revealed that while co-treatment of the cells with 7-BIO and MPP+ did not alter the toxicity induced by MPP+, pretreatment with 3.5 µM 7-BIO for 6 h increased the survival of the 2 mM MPP+ treated cells. Also, qRT-PCR analysis of gene expression showed that while miR-29a-3p was unchanged in cells treated with either 2 mM MPP+ or 3.5 µM 7-BIO alone, miR-34a-5p was increased by MPP+ but decreased by 7-BIO. Pretreatment with 3.5 µM 7-BIO prior to MPP+ however, increased miR-29a-3p but decreased miR-34a-5p induced by MPP+. We therefore suggest that 7-BIO inhibition of GSK3ß alleviates the MPP+ induced neurotoxicity by regulating miR-29a-3p and miR-34a-5p expressions in Parkinson's disease model SH-SY5Y cells.

2.
Acta Neurobiol Exp (Wars) ; 81(2): 171-180, 2021.
Article in English | MEDLINE | ID: mdl-34170264

ABSTRACT

Evidence suggests that transcranial direct current stimulation (tDCS) modulates conditioned fear memories and has effects on cognitive flexibility via the dopaminergic system. This study examines whether modulation of scopolamine­induced fear memory deficit by anodal tDCS could be mediated by the dopaminergic system. The male NMRI mice received scopolamine, 30 min before fear conditioning, and showed impaired contextual memory retention. Mice subjected to left frontal anodal stimulation for 20 or 30 min, before fear conditioning, impaired fear memory retrieval. Anodal application for 20 min significantly decreased scopolamine response on fear retention, while the one applied for 30 min did not alter. Moreover, anodal stimulation for 30 min abolished scopolamine­induced fear memory deficit. Dopaminergic antagonists SCH23390 and sulpiride, alone or in combination, prevented the abolishment effect of anodal stimulation on scopolamine­induced fear memory deficit, whereas they did not alter the impairing effect of scopolamine at the dose of 2 mg/kg. Our data suggest that anodal stimulation for 30 min abrogates the impairing effect of scopolamine on fear memory retention. This influence could be prevented by dopaminergic antagonists, indicating the involvement of the dopaminergic system in the effect of anodal stimulation on scopolamine­induced fear memory deficit.


Subject(s)
Dopaminergic Neurons/drug effects , Fear/drug effects , Memory Disorders/drug therapy , Memory/drug effects , Prefrontal Cortex/drug effects , Animals , Fear/physiology , Frontal Lobe/drug effects , Male , Memory Disorders/chemically induced , Mice , Prefrontal Cortex/physiology , Scopolamine/pharmacology , Transcranial Direct Current Stimulation/methods
3.
Immunobiology ; 224(2): 262-269, 2019 03.
Article in English | MEDLINE | ID: mdl-30579628

ABSTRACT

The most bacterial cause of infectious diseases associated with diarrhea are enterotoxigenic and enterohemorrhagic Escherichia coli (ETEC and EHEC, respectively). These strains use colonization factors for the attachment to the human intestinal mucosa, followed by enterotoxins production that could induce more host damage. The Heat-labile enterotoxin (LT) and colonization factors (CFs) are momentous factors for the pathogenesis of ETEC. Also, Intimin and Shiga like toxin (STX) are the main pathogenic factors expressed by EHEC. Because of mucosal surfaces are the major entry site for these pathogens, oral immunization with providing the protective secretary IgA antibody (sIgA) responses in the mucosa, could prevent the bacterial adherence to the intestine. In this study oral immunogenicity of a synthetic recombinant protein containing StxB, Intimin, CfaB and LtB (SICL) was investigated. For specific expression in canola seeds, the optimized gene was cloned in to plant expression vector containing the Fatty Acid Elongase (FAE) promoter. The evaluation of the expression level in canola seeds was approximately 0.4% of total soluble protein (TSP). Following to oral immunization of mice, serum IgG and fecal IgA antibody responses induced. Caco-2 cell binding assay with ETEC shows that the sera from immunized mice could neutralize the attachment properties of toxigenic E. coli. The reduction of bacterial shedding after the challenge of immunized mice with E. coli O157:H7 was significant. The sera from immunized mice in the rabbit ileal loop experiment exhibited a significant decrease in the fluid accumulation compared to the control. The results indicate efficacy of the recombinant chimeric protein SICL in transgenic canola seed as an effective immunogen, which elicits both systemic and mucosal immune responses as well as protection against EHEC and ETEC adherence and toxicity.


Subject(s)
Bacterial Vaccines/immunology , Escherichia coli Infections/prevention & control , Escherichia coli O157/immunology , Vaccines, Edible/immunology , Administration, Oral , Animals , Antibodies, Bacterial/immunology , Antibodies, Neutralizing/immunology , Bacterial Vaccines/administration & dosage , Immunity, Humoral , Immunity, Mucosal , Immunization , Mice , Neutralization Tests , Plants, Genetically Modified , Recombinant Fusion Proteins/immunology , Vaccines, Edible/administration & dosage
4.
Mol Med Rep ; 17(1): 1901-1906, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29138831

ABSTRACT

Migri­Heal®, is a novel herbal remedy that was introduced for the treatment of migraine headaches. Previous studies revealed that this drug may reduce nitric oxide (NO) in an in vitro inflammatory model. The aim of the present study was to investigate the anti­inflammatory effect of Migri­Heal® on primary mix glial cells stimulated with LPS. In the current study, neonatal rat primary mix glial cells were isolated from the mixed glial cultures via shaking, and cultured in Dulbecco's' modified Eagle's medium supplemented with 10% fetal bovine serum. Following pretreatment with Migri­Heal® (25, 75, 100, 150, 200 and 300 µg/ml) and cells were treated with LPS (10 µg/ml) for 1 h, and incubated for 48 h. The present study determined that 150 µg/ml Migri­Heal® significantly reduced the production of NO in rat mix glial cells stimulated with 10 µg/ml LPS. Migri­Heal® also suppressed mRNA expression level of LPS­induced inducible nitric oxide synthase and tumor necrosis factor α, which was accompanied by inhibition of the transcription factor nuclear factor­κB. Additionally, MTT assay determined that Migri­Heal® was not cytotoxic, suggesting that the anti­inflammatory effects of Migri­Heal® observed were not due to cell death. In conclusion, the findings of the present study demonstrated that Migri­Heal® may be useful as a potential anti­inflammatory agent in inflammatory diseases. However, additional studies are required to confirm these findings.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Neuroglia/drug effects , Plant Preparations/pharmacology , Animals , Cell Survival/drug effects , Cells, Cultured , Lipopolysaccharides/pharmacology , NF-kappa B/metabolism , Neuroglia/immunology , Nitric Oxide/metabolism , Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism , Rats, Wistar
5.
Int J Oral Maxillofac Implants ; 32(6): 1266-1272, 2017.
Article in English | MEDLINE | ID: mdl-29140371

ABSTRACT

PURPOSE: Titanium-based biomaterials present good biocompatibility, while their osseointegration and antibacterial properties need to be improved. This study aimed to enhance the bone-bonding ability of titanium-based granules, which are intended to be used as bone graft. MATERIALS AND METHODS: The titanium granules were anodized in ethylene glycol-based electrolyte and subsequently annealed to be loaded separately with simvastatin. The samples were then inspected with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) for drug loading. The release of simvastatin from titanium granule samples was measured after soaking samples in phosphate-buffered saline (PBS) for 30 days using ultraviolet-visible (UV/Vis) spectroscopy. The alkaline phosphatase (ALP) activity of MG63 osteosarcoma-loaded samples was measured, and microbroth dilution assay was performed to evaluate the antibacterial potential of drug-loaded and nonloaded titanium granule samples for bacterial growth. RESULTS: The results expressed the gradual and constant release of simvastatin within the duration of the examination. ALP of the samples showed improved activity of anodized and annealed granules, while the antibacterial test illustrated no significant improvement in their bactericidal effects. However, the simvastatin-loaded samples showed an improved antibacterial effect compared with nonloaded samples. CONCLUSION: It is assumed that anodizing, annealing, and subsequent simvastatin loading of titanium granules could be used as surface modification to improve osseointegration and restrain bacterial growth and adhesion. It is fair to believe that the results of this study could be used to treat titanium granules as bone graft substitute materials for dental and orthopedic applications.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Coated Materials, Biocompatible , Drug Delivery Systems/methods , Escherichia coli/drug effects , Osteogenesis/drug effects , Simvastatin/administration & dosage , Titanium/chemistry , Biocompatible Materials/chemical synthesis , Colony Count, Microbial , Escherichia coli/growth & development , Humans , Microscopy, Electron, Scanning , Osseointegration/drug effects , Osteosarcoma/diagnostic imaging , Osteosarcoma/pathology , Spectroscopy, Fourier Transform Infrared , Surface Properties
6.
Iran J Basic Med Sci ; 20(6): 623-630, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28868118

ABSTRACT

OBJECTIVES: Behavioral and neuroimaging studies have shown that transcranial direct current stimulation, as a non-invasive neuromodulatory technique, beyond regional effects can modify functionally interconnected remote cortical and subcortical areas. In this study, we hypothesized that the induced changes in cortical excitability following the application of cathodal or anodal tDCS over the left frontal cortex as pre-training would affect functional connectivity in resting-state circuits of fear memory and consequently could improve or disturb the acquisition of fear memory. MATERIALS AND METHODS: In order to evaluate the polarity-dependent effects of tDCS on the acquisition of fear memory and the functional connectivity, we applied left prefrontal anodal or cathodal stimulation at 200 µA for one session to healthy mice for the durations of 20 and 30 min prior to fear conditioning. RESULTS: Our results revealed that the administration of left prefrontal anodal (for both 20 and 30 min durations) and cathodal (at 30 min duration) tDCS impaired the acquisition of both contextual and cued fear memory. In addition, we did not observe a direct correlation between stimulation duration and the efficacy of tDCS on the acquisition of contextual and cued fear memory. CONCLUSION: In this study, the impairments of both contextual and cued memory further confirmed the previous studies reporting that the administration of transcranial stimulation would affect the activity of deeper structures like amygdala and hippocampus as the main components of the fear memory circuit in acquisition, storage, and expression of the memory.

7.
Iran Biomed J ; 16(2): 84-9, 2012.
Article in English | MEDLINE | ID: mdl-22801281

ABSTRACT

BACKGROUND: Neuroinflammation, as a major outcome of microglia activation, is an important factor for progression of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. Microglial cells, as the first-line defense in the central nervous system, act as a source of neurotoxic factors such as nitric oxide (NO), a free radical which is involved in neuronal cell death. The aim of this study was to inhibit production of NO in activated microglial cells in order to decrease neurological damages that threat the central nervous system. METHODS: An in vitro model of a newborn rat brain cell culture was used to examine the effect of betaine on the release of NO induced by lipopolysaccharide (LPS). Briefly, primary microglial cells were stimulated by LPS and after 2 minutes, they were treated by different concentrations of betaine. The production of NO was assessed by the Griess assay while cell viability was determined by the MTT assay. RESULTS: Our investigations indicated that LPS-induced NO release was attenuated by betaine, suggesting that this compound might inhibit NO release. The effects of betaine on NO production in activated microglial cells after 24 h were "dose-dependent". It means that microglial cells which were treated with higher concentrations of betaine, released lower amounts of NO. Also our observations showed that betaine compound has no toxic effect on microglial cells. CONCLUSION: Betaine has an inhibitory effect on NO release in activated microglial cells and may be an effective therapeutic component to control neurological disorders.


Subject(s)
Betaine/pharmacology , Lipotropic Agents/pharmacology , Microglia/metabolism , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Nitric Oxide/metabolism , Animals , Cell Survival/drug effects , Cells, Cultured , Lipopolysaccharides , Rats , Rats, Wistar
8.
Virol J ; 6: 209, 2009 Nov 26.
Article in English | MEDLINE | ID: mdl-19939285

ABSTRACT

The core protein of hepatitis B virus encompasses B- and T-cell immunodominant epitopes and subdivided into two domains: the N-terminal and the functional C-terminal consisted phosphorylation sites. Mutations of the core gene may change the conformation of the core protein or cause alteration of important epitopes in the host immune response. In this study twenty nine men (mean age 40 +/- 9 years old) with chronic hepatitis B were recruited for direct sequencing of the core gene. Serum ALT and HBV DNA level were measured at the time of liver biopsy. The effects of core protein mutations on patients' characteristics and subsequently mutations in B cell, T helper and cytotoxic T lymphocyte (CTL) epitopes and also C-terminal domain of core protein on the activity of liver disease was evaluated. Liver fibrosis was significantly increased in patients with core protein mutation (1.0 +/- 0.8 vs 1.9 +/- 1.4 for mean stage of fibrosis P = 0.05). Mutations in CTL epitopes and in phosphorylation sites of C-terminal domain of core protein also were associated with higher liver fibrosis (P = 0.003 and P = 0.04; Fisher's exact test for both). Patients with mutation in C-terminal domain had higher serum ALT (62 +/- 17 vs 36 +/- 12 IU/l, p = 0.02). Patients with mutations in B cell and T helper epitopes did not show significant difference in the clinical features. Our data suggests that core protein mutations in CTL epitopes and C-terminal domain accompanied with higher stage of liver fibrosis may be due to alterations in the function of core protein.


Subject(s)
Hepatitis B virus/genetics , Hepatitis B, Chronic/virology , Liver Cirrhosis/virology , Mutation , Viral Core Proteins/genetics , Adult , CD13 Antigens/blood , DNA, Viral/blood , DNA, Viral/genetics , Epitopes, T-Lymphocyte/immunology , Hepatitis B virus/immunology , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/immunology , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/etiology , Liver Cirrhosis/immunology , Male , T-Lymphocytes, Cytotoxic/immunology
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