immunology & Biochemistry
hassan Ramshini
Volume 28, Issue 2 , May and June 2021, , Pages 232-241
Abstract
Introduction: The accumulation of amyloid aggregates in the brain are associated with numerous neurodegenerative disorders. Several nanoparticles (NP) have been using for treatment of neurological disease. Metal nanoparticles can be modified through the construction of bimetallic architectures consisting ...
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Introduction: The accumulation of amyloid aggregates in the brain are associated with numerous neurodegenerative disorders. Several nanoparticles (NP) have been using for treatment of neurological disease. Metal nanoparticles can be modified through the construction of bimetallic architectures consisting of two distinct metals that their properties can be dramatically different from those of the corresponding single-component particles. At the present study, we evaluated the effect of the bimetallic Au/Ag nanoparticles on hen lysozyme amyloid aggregation as a model protein for amyloid formation . Materials and Methods: In this experimental study, to induce amyloid formation, Acidic pH and high temperatures were used. Hen egg white lysozyme (HEWL) was dissolved at 2 mg/mL in 50mM glycine buffer (pH 2.5), and then incubated at 57 °C for the specified durations. The inhibitory effect of the nanoparticles against HEWL fibrillation using and ThT (thioflavin T), Congo red and MTT assay was investigated . Results: ThT assay showed that the particles are able to inhibit HEWL aggregation in a pattern of inverse dose-dependent inhibition and with the best inhibitory concentration 0.01 µg/ml. Kinetic study of showed that the particles caused lag phase do not change but stationary phase decreased and also cytotoxic activity of HEWL aggregates in presence of Au/Ag nanoparticleswas significantly diminished (P˂0.05) . Conclusions: We anticipate that based on obtained insights in design of new bimetallic nanoparticles, rationally design of effective NP-based therapeutics for neurodegenerative diseases may be a feasible perspective .
Internal Medicine
hassan Ramshini; afsaneh kaffash
Volume 27, Issue 6 , January and February 2021, , Pages 852-859
Abstract
Introduction: The coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2, has become the current health concern to the entire world. Initially appeared in Wuhan, China around December 2019, it spread to almost 216 countries due to its high contagious nature, so the World ...
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Introduction: The coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2, has become the current health concern to the entire world. Initially appeared in Wuhan, China around December 2019, it spread to almost 216 countries due to its high contagious nature, so the World Health Organization recently declared the pandemic feature of the infection. SARS-CoV-2(COVID-19) which is genetically similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) is an enveloped, single and positive-stranded RNA virus with a genome comprising 29,891 nucleotides, which encode the 12 putative open reading frames responsible for the synthesis of viral structural and nonstructural proteins which are very similar to SARS-CoV and MERS-CoV proteins. Currently, there are no approved treatments for COVID-19. For this reason, we reviewed existing publications about Coronavirus Disease 2019 (COVID-19) regarding epidemiology, pathophysiology, diagnosis and treatments. Materials and Methods: Given the various investigations on the Virus (15928 publications in MEDLINE database, Until May 26, 2020) and various clinical data generated by the large number of laboratories, clinicians need accurate evidence regarding effective medical treatments for this infection. In this review, MEDLINE, SCIENCE DIRECT and Scopus databases were searched for relevant articles. Results: Since the emergence of COVID-19 infection there was a large interest in the development of an effective therapy for this disease. In this review, we summarized the available literature on possible therapeutic options including in vitro, animal and human studies. This review has presented a picture of the current findings on the epidemiology, clinical features, diagnosis, management, and prevention of COVID-19. Conclusion: The COVID-19 epidemic represents the world's biggest public health crisis. Clinical trials that have begun to look for potential treatments for COVID-19 are very high, but unfortunately have not yet led to the development of an effective drug. Thus, to overcome on this crisis preventive and coordinated emergency measures between all countries are needed.
immunology & Biochemistry
Hassan Ramshini; Shahryar Saeidian; Leila Nazemian
Volume 27, Issue 1 , May and June 2020, , Pages 55-63
Abstract
Backgrounds & Objectives: Alzheimer's disease is of major concern all over the world due to a number of factors including (i) an aging population (ii) increasing life span and (iii) lack of effective pharmacotherapy options. Aromatic small molecules have been found to play a neuroprotective role ...
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Backgrounds & Objectives: Alzheimer's disease is of major concern all over the world due to a number of factors including (i) an aging population (ii) increasing life span and (iii) lack of effective pharmacotherapy options. Aromatic small molecules have been found to play a neuroprotective role by inhibiting and/or modifying the self-assembly of peptide or proteins into oligomers and fibrils, which are linked to the pathogenesis of the diseases. In this study, the inhibitory effects of 1,3, 5 triphenyl benzene as an aromatic molecule on aggregation and neurotoxicity of hen egg white lysozyme (HEWL) was investigated.Methods: Acidic pH and high temperatures were used to drive the protein towards amyloid formation. Lysozyme was dissolved at 2 mg/mL in 50mM glycine buffer (pH 2.5), and then incubated at 57 °C for the specified durations. The inhibitory effect of the compounds against hen egg white lysozyme (HEWL) fibrillation using AFM (atomic force microscope), ThT (thioflavin T), Congo red and MTT assay was investigated.Results: We found that the compounds is able to inhibit HEWL aggregation in a dose-dependent manner with IC50 0.1 µM. Kinetic study of the compound caused lag phase prolonged and stationary phase decreased and also cytotoxic activity of HEWL aggregates in presence of the compounds was diminished.Conclusions: These observations suggest that 1,3,5 triphenyl benzene is capable to insert directly into amyloidogenic core of early aggregates and inhibiting amyloid fibril formation.
Hasan Ramshini; Abdollah Mehrabadi; Alireza Moslem
Volume 23, Issue 1 , May and June 2016, , Pages 183-195
Abstract
Backgrounds & Objectives: Aggregates of β-amyloid protein are the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer's disease (AD). Compounds that could inhibit Aβ fibrils formation and or reduce their associated neurotoxicity ...
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Backgrounds & Objectives: Aggregates of β-amyloid protein are the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer's disease (AD). Compounds that could inhibit Aβ fibrils formation and or reduce their associated neurotoxicity might have therapeutic values for treating AD. Although curcumin has shown promising therapeutic utilities for many diseases, including Alzheimer, its clinical application is severely limited because of its poor stability under physiological conditions. In this study, the inhibitory effects of 2,6-bis(3,4-dimethoxybenzylidene)-1-cyclohexanone on aggregation and neurotoxicity of hen egg white lysozyme (HEWL) and, also, on spatial learning and memory of rats were evaluated. Methods: 30 male wistar rates (250-280 g) were divided into 5 groups: control, received scopolamine, received lysozyme amyloid aggregates, received lysozyme aggregates formed in presence of Curcumin and/or Curcumin derivative. The Morris Water maze was used for studying the spatial learning memory. Results: The results showed that, in comparison with receiver groups of lysozyme aggregates alone, the receiver rats of the aggregates formed in the presence curcumin and its derivative found platform in less time and with less distance traveled. The hippocampal injection of HEWL aggregates damaged the spatial memory of rates. Meanwhile amyloid aggregates formed in presence of curcumin or curcumin derivative were nontoxic and had no significant effect on spatial memory in rats. Conclusions: These observations suggest that Curcumin and its derivativeare are capable to insert directly into amyloidogenic core of early aggregates and inhibiting amyloid fibril formation. Also, this study showed the importance of using model proteins as a valid tool to investigate the pathogenesis of Alzheimer’s disease.
Abolfazl Rad; Seyyed Mehdi Beheshti nasr; Hasan Ramshini
Volume 21, Issue 5 , September and October 2014, , Pages 711-718
Abstract
Background and purpose: Minocycline has got the anti-inflammatory and neuroprotective effects. Considering the interaction between cell death and seizure, and on the other hand, Kindling which increases expression NMDA receptors in brain, the aim of this study is to investigate the effect of minocycline ...
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Background and purpose: Minocycline has got the anti-inflammatory and neuroprotective effects. Considering the interaction between cell death and seizure, and on the other hand, Kindling which increases expression NMDA receptors in brain, the aim of this study is to investigate the effect of minocycline on gene expression of NMDA receptor in hippocampus and piriform brain areas on amygdale kindling acquisition in rats.
Materials and Methods: In this experimental study, three animal groups of 24 Wistar rats received kindling stimulations (twice daily within 6 hours intervals) after being stereotaxic operated and taking one week recovery period. In first Group (n=8) animals did not received daily kindling stimulations. Animals of the second and the third Groups (n=8) respectively had been injected by saline (1ml/kg) and minocycline (25 mg/kg), 60 minutes before receiving kindling stimulations. Two hours after last stimulation animal’s brains were removed and the changes of NR2A gene subunit of NMDA receptor in the hippocampus and piriform cortex were measured and compared relative to the control group. Datawere analyzed using ANOVA and Tukey post hoc tests at significant level of P
Seyed Mehdi Beheshti Nasr; Mohammad Mohammadzadeh; Hasan Ramshini
Volume 21, Issue 2 , May and June 2014, , Pages 352-361
Abstract
Introduction: Minocycline has anticonvulsant effects. Since some antiepileptic drugs increase the neurotransmitter GABA in the brain, the aim of this study is the effect of minocycline on gene expression of GABAA receptor in hippocampus and piriform brain areas on amygdale kindling acquisition in rat.
Methods: ...
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Introduction: Minocycline has anticonvulsant effects. Since some antiepileptic drugs increase the neurotransmitter GABA in the brain, the aim of this study is the effect of minocycline on gene expression of GABAA receptor in hippocampus and piriform brain areas on amygdale kindling acquisition in rat.
Methods: In this experimental study, three group (24 Wistar rats), after stereotaxic surgery and 1 week recovery period, received kindling stimulations(twice daily at 6 hours interval). Group 1(n=8) did not receive daily kindling stimulations. Group 2 (n=8) received intraperitoneal saline (1ml/kg) and Group 3 (n=8) received intraperitoeneal minocycline (25 mg/kg) 60 min before kindling stimulation and respectively. Two hours after the last stimulation, animals’ brains were removed and the changes of gene expression by γ2 subunit of GABAAreceptor in the hippocampus and piriform cortex were measured and compared with the control group. Data was analyzed using one-way ANOVA and Tukey post hoc tests (P
Hasan Ramshini
Volume 19, Issue 3 , September and October 2012, , Pages 238-248
Abstract
Background: In brain tumors, the main source of energy is from glycolysis, which is initiated by hexokinase type I (HK-I), an enzyme bound to the outer mitochondrial membrane, involving two sets of binding sites. In addition to the glucose-6-phosphate (G6P)-sensitive site (Type A), the enzyme is bound ...
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Background: In brain tumors, the main source of energy is from glycolysis, which is initiated by hexokinase type I (HK-I), an enzyme bound to the outer mitochondrial membrane, involving two sets of binding sites. In addition to the glucose-6-phosphate (G6P)-sensitive site (Type A), the enzyme is bound on a second set of sites (Type B) which are insensitive to G6P, but totally releasable by high concentrations of chaotropic salts such as KSCN. In the present study, we investigate possible changes in HK-I binding to the outer mitochondrial membrane during malignancy. Materials and Methods: In this experimental study, 2 mM G6P was used for releasing enzyme from site A, while site B was depleted using a mixture of KSCN and KCl with a total concentration of 45 mM. For blocking binding sites in site A, dicyclohexylcarbodiimide (DCCD) was used. Results: DCCD, which normally has the capacity to block HK-I binding at site A, was found ineffective for mitochondria obtained from astrocytoma and glioma specimens, presumably due to changes in the microenvironment of Glu 72 of porin with which it interacts. It also appears that increased incorporation of cholesterol, reported to occur in the mitochondria of cancer cells, may influence HK binding due to changes in mitochondrial membrane fluidity. Conclusion: Taken together, these results support earlier conclusions on possible changes in the microenvironment of bound HK-I and also fluidity of membrane upon malignancy.
Hasan Ramshini
Volume 18, Issue 2 , July and August 2011, , Pages 71-81
Abstract
Background and Purpose: Formation of well-ordered fibrillar protein deposits is common to a large group of amyloid-associated disorders، including Alzheimer’s، Parkinson’s، type II diabetes and prion diseases. The nature of the pathogenic species and the mechanism by which the aggregation process ...
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Background and Purpose: Formation of well-ordered fibrillar protein deposits is common to a large group of amyloid-associated disorders، including Alzheimer’s، Parkinson’s، type II diabetes and prion diseases. The nature of the pathogenic species and the mechanism by which the aggregation process results in cell damage are، however، not well established. In the present study، the propensity of hexokinase type B from Saccharomyces cerevisiae (YHKB) to form amyloid-like and amorphous aggregates is investigated under various conditions and their cytotoxicity is determined.
Methods and Materials: In this experimental study، Amyloid-like aggregation was induced under three different conventional conditions including the preincubation of YHKB (1) in acidic pH، at 55 ºC and with agitation، (2) in acidic pH، room temperature، in presence of salt and without agitation، and (3) in the presence of trifluoroethanol (TFE). Types of aggregates in above conditions were compared for their capability to react with ThT (as a amyloid marker) and their morphology was analyzed by atomic force microscopy (AFM). Also، Cytotoxicity of the aggregates on human neuroblastoma (SH-SY5Y) were assayed by MTT reduction assay test.
Results: Aggregates produced under all three conditions had ThT binding ability but with different intensity. Atomic force microscopy indicated that aggregates morphologies in various conditions were completely different. Amorphous aggregates of the enzyme were also produced for comparing with ordered aggregates. Amorphous aggregates were not found toxic to human neuroblastoma cells، as indicated by the MTT reduction assay while those formed at acidic pH and in the presence of TFE indicated cytotoxicity.
Conclusions: Based on the findings، differences in cytotoxicity can be attributed to the variations in the nature and morphology of the aggregates in the conditions tested.