شهین احمدیان

Amyloid fibrils are string-like aggregates that form due to the disruption of natural structure and misfolding of various types of peptides and proteins. These amyloid aggregates are associated with some neurodegenerative and systemic diseases such as Alzheimer's, Parkinson's, and type 2 diabetes. The aim of this study was to investigate the inhibitory effects of Trans-chalcone on insulin fibrillation (as a model protein). In this study, insulin was incubated for 24 hours in the presence and absence of Trans-chalcone under amyloid formation conditions. The formed fibrils were analyzed using various techniques including Congo red absorption spectral changes by spectroscopy, electron microscopy images by TEM, and fluorescent staining of amyloid aggregates by fluorescent microscopy. Then, possible interactions between Trans-chalcone and insulin were analyzed using molecular docking method by AutoDock software. The results showed a significant reduction in amyloid fibril formation in the additive-containing sample compared to the control sample. This study provides evidence that Trans-chalcone has an inhibitory effect on insulin fibrillation and could be a potential therapeutic agent for amyloid-related diseases.

Alzheimer's disease is a neurodegenerative disorder that results in neuronal death and memory loss as it progresses. Following the progression of this disease, the production of free radicals and inflammatory factors occurs and it is now increasingly widespread, especially among the elderly. Studies show that Bornyl acetate, as a monoterpene, has antioxidant and anti-inflammatory effects. Therefore, the present study aims at assessing the effects of Bornyl acetate on AD male Wistar rats. Aβ1-42 was injected into the hippocampus of male rats bilaterally to create the Alzheimer's model. The therapeutic as well as the preventive effects of Bornyl acetate at a dosage (50, 20 mg/kg) were also investigated. Moreover, biochemical enzymes, SOD and MDA, shuttle box behavioral test, histological studies and hematoxylin & eosin and thioflavin-S staining were used to evaluate neurogenesis and amyloid plaques and the effects of short-term restraint stress on AD rats as well as the effects of the compound in vitro. Biochemical factors, histological images and behavioral test of the AD group were significantly different from the control groups and AD group showed a significant decline in learning and memory indices compared with the control group. Also, receiving a Bornyl acetate caused a significant increase in neurogenesis and a significant decrease in plaque density as well as significant changes in biochemical indices and behavioral tests. In addition, Bornyl acetate + restraint stress (R) group elevated learning speed and improved memory compared with the AD group. Notably, the above combination reduced amyloid fibrils in vitro. It seems that this compound can improve memory disorders and complications according to the results of the present study and previous reports suggest the anti-inflammatory and antioxidant effects of Bornyl acetate.

Alzheimer’s disease is one of the most important neurodegenerative diseases occurring after the production of free radicals and inflammatory factors. Geraniol, which is a natural monoterpene, contains antioxidant and anti-inflammatory effects. The aim of this study was to investigate the effects of Geraniol and exercise on memory and learning, SOD activity and MDA serum level, neurogenesis and amyloid plaque count in Alzheimer’s Wistar rats. To create the Alzheimer's disease model, Aβ 1-42 was injected bilaterally into the hippocampus of male rats. Grouping included control (-), control (+), exercise, Alzheimer, Alzheimer + exercise, Alzheimer + Geraniol, and Alzheimer + Geraniol + exercise. The results showed that SOD activity and MDA serum level were significantly increased in the Alzheimer + Geraniol, Alzheimer + exercise, and Alzheimer + Geraniol + exercise groups compared to other groups (P<0.001). In addition, shuttle box behavioral test demonstrated that the entry time to the dark box was notably increased in Alzheimer + Geraniol and Alzheimer + Geraniol + exercise groups compared to Alzheimer and Alzheimer + exercise groups (P<0.001). Moreover, neurogenesis was remarkably increased in Alzheimer + Geraniol and Alzheimer + Geraniol + exercise groups compared to Alzheimer and Alzheimer + exercise groups (P<0.001). Besides, the number of amyloid plaques was decreased Alzheimer + Geraniol and Alzheimer + Geraniol + exercise groups compared to other groups (P<0.001). Based on the results of this study, it seems that this compound along with exercise is notably capable of improving complications in memory, SOD activity, MDA serum level, and neurogenesis as well as amyloid plaques in Alzheimer’s disease.

Alzheimer's disease is one of the most important neurodegenerative diseases that occur following the production of free radicals and inflammatory factors. Terpinolene has antioxidant and anti-inflammatory effects. This study aimed to investigate the effects of terpinolene and physical activity on memory and learning in a model of Alzheimer's rats.

Bilateral injection of AB1-42 was administered to the hippocampus of the male rats to create the model of Alzheimer's disease. The assigned groups included control (-), sham, exercise, control (+), Alzheimer's+distilled water, Alzheimer's+exercise, Alzheimer's+terpinolene (treatment), Alzheimer's+terpinolene (prevention), and Alzheimer's+terpinolene+exercise. Superoxide dismutase (SOD), Malondialdehyde (MDA) level, shuttle box behavioral test, as well as neurogenesis and amyloid plaques were assessed in this study. The data were statistically analyzed using oneway ANOVA.

The SOD activity and neurogenesis levels decreased significantly in the control (+) group, compared to control groups of the behavioral test. However, the MDA level and plaque increased significantly (P<0.05). Terpinolene intake and exercise caused a significant increase in neurogenesis, a significant decrease in plaques, and significant changes in biochemical and behavioral parameters (P<0.05).

Based on the results of this study and previous reports on the antioxidant and anti-inflammatory effects of terpinolene and exercise, it seems that this combination along with exercise can improve memory complications and disorders.

Autophagy is a survival pathway required for cellular viability during starvation through catabolic self digestion of damaged proteins and organelles; however, autophagy may result in cell death if it proceeds to completion. Although the exact mechanism of this process is not clear, it seems that proper regulation of autophagy can potentially contribute to the therapeutics of cancers. The aim of this study was to determine the role of Arsenic trioxide (As2O3) in the induction of autophagy in human acute promyelocytic leukemia.

In this study, the role of autophagy in the As2O3-induced death of NB4 cells was assessed using electron microscopy. Also, quantitative real-time PCR method was used for expression of autophagy related genes in dose and Time dependent manner.

Our results showed that autophagy induces death in NB4 cells treated with arsenic trioxide. It was also found that the Atg7, Bclin1 and LC3 genes, which are essential genes for induction of autophagy, are the target of arsenic trioxide invasion.

This study showed As2O3-induced autophagy plays an important role in eliminating leukemia cells and treatment of cancer.

In the recent decades, there has been an increasing effort to study possible biological effects of extremely low frequency electromagnetic fields (ELF-EMFs). In this study, the effects of 50 Hz, 0.6 mT pulsed electromagnetic field on proliferation and biochemical properties, in a prostate cancer cell line, DU-145, and the simultaneous treatment of these cells with electromagnetic field and anticancer drug, berberine, were explored Control and treated cells were seeded in separate plate dishes and cell proliferation, concentration of reactive oxygen species (ROS), survivin expression and DNA damage were studied by MTT assay, Fluorescence spectrometry, Western blotting and Comet assay, respectively. Our results showed a significant increment in cell proliferation and intracellular concentration of ROS after 24-72 hours of continuous exposure to the field. The treatment did not affect the expression level of the cancer biomarker, survivin, but acted as a genotoxic agent and increased DNA single and double strand damages. The results also showed that continuous exposure to the applied field does not have any effect on the cytotoxic activity of berberine in DU-145 cells. On the whole, it seems that the studied electromagnetic field acts as a tumor promoter in this cell line, possibly through induction of oxidative stress and DNA damage.

Recent findings demonstrate that oligomeric species, as toxic intermediates during the formation of mature fibrils, by increasing membrane permeability leading to cell death. Among these, the membrane of interest is mitochondria, so that mitochondrial dysfunction is a common feature of many disorders relating to protein aggregation. Therefore, in the present study interaction of the original native structure, oligomeric intermediates and amyloid fibrils of hen egg white lysozyme (HEWL) with mitochondrial membranes (as an in vitro biological model) were investigated. First structural characteristics of prefibrillar intermediates have been investigated using a range of techniques including fluorescence (ThT and ANS) and circular dichroism, and possible mitochondrial membrane permeabilization was determined following release of marker enzymes. Results presented demonstrate release of mitochondrial enzymes upon exposure to HEWL oligomers, whereas native monomer or mature fibrils were totally ineffective. It seems that increased surface hydrophobicity of HEWL oligomers enhanced their capacity to interact with mitochondrial membranes. Then we investigated the ability of Resveratrol to counteract mitochondrial membrane permeabilization induced by HEWL oligomers. The results demonstrate that Resveratrol can effectively hinder oligomer-mediated mitochondrial permeabilization. It has been suggests that Resveratrol via its membrane stabilizing effects protects mitochondria against oligomer toxicity. These may serve for design of novel therapeutic agents against disorders relating to protein misfolding and aggregation

Accumulations of biogenic magnetite (Fe3O4) in the brain and dysregulation of iron transport and storage have been found to be associated with many neurodegenerative disorders, such as Alzheimer disease. AD is a progressive neurodegenerative disorder that causes disruptions in memory and cognition. Several studies have shown that pathogenesis of AD is also related to protein misfolding and aggregation of tau protein in the brain. Microtubule-associated tau protein belongs to a family of intrinsically disordered proteins that promotes microtubule assembly and stability. In the present study, we investigated the interaction between recombinant human tau and magnetic iron nanoparticles by using ThT fuorescence and transmission electron microscopy. Our results showed that magnetic iron nanoparticles induced tau conformational changes from random-coil to β-sheet and consequently resulted in the formation of tau fibrils. In conclusion, our results proposes a probable mechanism for the correlation between aggregation of tau protein and biogenic magnetite crystals in AD.

Rotaviruses are recognized as the most important cause of sever diarrhea illness of infants and children world-wide. These viruses consist of triple-layered protein capsid The inner layer is composed of VP2. In this study, the expression of VP2 gene of the bovine rotavirus RF has been evaluated in human epithelial lung cells (A549) under CMV promoter. First, the rotavirus gene was cloned in pcDNA3 plasmid and then recombinant plasmid transferred to a human lung epithelial cell line by a carrier namely dendrosome. Western blotting analysis has revealed expression of the gene in the cells after 48-72 hrs post infection. The expression of VP2 gene was confirmed by observation of core like particles (CLPs) with electron microscopy and immunocytochemistry by using gold conjugated protein A. The results indicated that the used eukaryotic cells in this study can serve as a suitable host for expression of VP2 gene; since the cells expressed the proteins correctly and made the VP2 protein to be self-assembled and form native structure.

Microtubules are important components of cell cytoskeleton which participate in mitosis, protein localization and cell signaling. They are also the targets of several anticancer agents which indicating their importance in maintaining cell viability. Capacity of leukemia cells to re-organize their microtubules is considered an integral part of differentiation of these cells to mature granulocytes by all-trans retinoic acid (ATRA), which is an establish drug for treating acute promyelocytic leukemia. In this study we examined alpha-, alpha-acetylated and gamma-tubulin content, their patterns of distribution in the cytoplasm and the potency of centrosomes in reorganizing microtubules in different stages of ATRA-induced differentiation of HL-60 cell line. Results have shown that gamma-tubulin content was increased with a focal centrosomal accumulation of gamma-tubulin following differentiation. Differentiated cells had the ability to re-organize their microtubule network following nocodazole challenge test, whereas undifferentiated cells did not show such ability. Alpha-tubulin was more regularly organized in differentiated cells and acetylated alpha-tubulin generally followed the same organization patterns after differentiation as occurred for alpha-tubulin. Our results is suggestive of a centrosomal, and organized nucleation pattern of microtubules in HL-60 cells following differentiation possibly mediated through upregulation of gamma-tubulin.