Shahin Ahmadian | University of Tehran (original) (raw)

Papers by Shahin Ahmadian

European Journal of Human Genetics, 2019

PRPF31 is ubiquitously expressed splicing factor and has an essential role in the pre-mRNA splici... more PRPF31 is ubiquitously expressed splicing factor and has an essential role in the pre-mRNA splicing in all tissues. However, it is not clear how reduced expression of this general splicing factor leads to retinal restricted disease, retinitis pigmentosa (RP). In this study, we used RNA interference and RNA-sequencing to mimic the PRPF31 haploinsufficiency in human organotypic retinal cultures (HORCs). We examined the effects of PRPF31 deficiency on splicing by analyzing the differential exon usages (DEUs) and intron retentions of the retinal transcriptome. Our results revealed that the PRPF31 deficiency causes mis-splicing of genes involved in RNA processing (PRPF3, PRPF8, PRPF4, and PRPF19) and phototransduction (RHO, ROM1, FSCN2, GNAT2, and GNAT1) in the retina in the PRPF31 reduced samples. Mis-splicing of genes implicated in phototransduction was associated with photoreceptor degeneration observed in RP patients. Our data revealed that PRPF31 deficiency leads to the mis-splicing of a distinct subset of pre-mRNAs with a widespread effect on phototransduction and RNA processing.

ACS Biomaterials Science & Engineering, 2019

Molecular Biology Reports, 2019

Cisplatin is widely used as an anticancer drug in chemotherapy of human cancers. In the field of ... more Cisplatin is widely used as an anticancer drug in chemotherapy of human cancers. In the field of cancer therapy, nanoparticles modified with biocompatible copolymers are suitable vehicles to effectively deliver smaller doses of hydrophobic drugs such as cisplatin in the body. In this study, we investigated whether cisplatin-loaded iron oxide nanoparticles (IONPs) modified with chitosan can exert cytotoxic effects in the human breast cancer cell line MDA-MB-231. IONPs was synthesized using eucalyptus leaf extract as a reducing and stabilizing agent. MDA-MB-231 cells were treated with different concentrations of cisplatin, cisplatin-IONPs and cisplatin-IONPs-chitosan for 24 h. Apoptosis was confirmed by flow cytometry, whereas The mRNA and protein expression of pro-and anti-apoptotic molecules were measured using Real time RT-PCR and western blotting. Treatment with both cisplatin-IONPs and cisplatin-IONPs-chitosan showed a significantly higher cytotoxic effect in comparison to the free drug alone in MDA-MB-231 cells. The levels of apoptosis in cells treated with a combination of cisplatin-IONPs-chitosan were significantly higher compared with cisplatin-IONPs and cisplatin alone. The results of this study showed that the interaction between cisplatin and iron oxide nanoparticles modified with chitosan could enhance responsiveness to cisplatin in breast cancer cells.

European journal of pharmacology, Jan 5, 2018

Reactive oxygen species (ROS) are essential mediators of crucial cellular processes including apo... more Reactive oxygen species (ROS) are essential mediators of crucial cellular processes including apoptosis, proliferation, survival and cell cycle. Their regulatory role in cancer progression has seen in different human malignancies such as acute myeloid leukemia (AML). AML patients suffer from high resistance of the tumors against routine therapeutics including ATO. ATO enhance reactive oxygen species levels and induce apoptosis and suppresses proliferation in AML cells. However, some pathways such as JAK2/STAT3 ease anti-tumor activity of ATO by reducing reactive oxygen species amount and protecting the cell from apoptosis. In the present study, we use ruxolitinib (potent JAK2 inhibitor) to increase the sensitivity of AML cells to ATO treatment. We test, the effect of this combination on metabolic activity, proliferation, colony formation, cell cycle distribution, apoptosis, oxidative stress and DNA damage. Our results showed that combination of ATO with ruxolitinib synergistically r...

International journal of biological macromolecules, 2018

Ozone has been known for several decades, with its antiseptic and therapeutic effects determined ... more Ozone has been known for several decades, with its antiseptic and therapeutic effects determined by the hormesis theory. It is shown that the therapeutic efficacy of ozone therapy may be partly due to the controlled and moderate oxidative stress produced by the reaction of ozone with several biological components. In this study, the effect of ozone on healthy human hemoglobin (Hb) in the whole blood environment (in the presence of antioxidants) and in the purified form (in the absence of antioxidants) is investigated using a number of different techniques including intrinsic fluorescence, circular dichroism and UV-VIS absorption spectroscopy as well as SDS- and Native-PAGE and dynamic light scattering. The results show that the presence of antioxidants prevents damage to Hb while its absence means that as the exposure to ozone is increased, Hb is increasingly damaged. These results highlight the importance for the use of appropriate doses of ozone, for patients with different diseas...

PloS one, 2018

This study investigated for the first time the molecular effectiveness of 'aroma' from th... more This study investigated for the first time the molecular effectiveness of 'aroma' from three small molecules including a phenol (phenyl ethyl alcohol; PEA) and an aldehyde (cinnamaldehyde; Cin) both containing an aromatic ring, and a diamine (N,N,N,N'- Tetramethylethylenediamine; TEMED) at two different amounts (small; S and large; L) in preventing hen egg white lysozyme (HEWL) amyloid fibril formation using Thioflavin T and Nile red fluorescence assays, circular dichroism spectroscopy, SDS-polyacrylamide gel electrophoresis, atomic force microscopy, dynamic light scattering and HEWL activity test. Interestingly, the results revealed that (1) the aroma of PEA, identified as an active constituent of Rosa damascena, prevented fibril formation since PEA-L was able to trap the oligomeric form of HEWL in contrast to PEA-S where protofibrils but not mature fibrils were formed; (2) Cin, previously shown to prevent fibril formation in the liquid form, was also shown to do so in ...

European journal of pharmacology, Jan 5, 2018

Glioblastoma multiform (GBM) accounts for the most common form of primary brain tumors with very ... more Glioblastoma multiform (GBM) accounts for the most common form of primary brain tumors with very limited survival rate. Drug resistance is the main challenges for good prognosis of GBM patients. Arsenic trioxide (ATO) as a multifunctional drug has been investigated for the treatment of several solid tumors. Amplification/overexpression of the epidermal growth factor receptor (EGFR) gene as a signature genetic abnormality of GBM tumors can be a chemoresistance mechanism. In this study, we use erlotinib as an EGFR inhibitor to increase the sensitivity of GBM cell lines to ATO treatment. We evaluate the effects of this combination on metabolic activity, viability, cell proliferation, colony formation, cell cycle distribution, migration, oxidative stress and reactive oxygen species production. Our results showed that combination of ATO with erlotinib synergistically reduced metabolic activity, proliferation and colony forming potential in treated GBM cell lines. This combination induced...

Annals of hematology, Jan 20, 2017

PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation i... more PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4. Analysis of promoter methylation status of 22 cell cycle related genes in NB4 revealed that CCND1, CCNE1, CCNF, CDKN1A, GADD45α, and RBL1 genes were methylated 60.7, 84.6, 58.6, 8.7, 33.4, and 73.7%, respectively, that after treatment with 2 μM ATO for 48 h, turn into 0.6, 13.8, 0.1, 6.6, 10.7, and 54.5% methy...

Nutritional neuroscience, Jan 9, 2017

Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treat... more Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treatment of chronic conditions, including cancer and neurodegenerative disorders. Accordingly, in the present study, we aimed at evaluating the effects of oral intake of two structurally different flavonoids 5-hydroxy-6,7,4'-trimethoxyflavone (flavone 1) and 5,7,4'-trihydroxyflavone (flavone 2) on recognition memory, hippocampal protein level of immediate early gene cFos and mitochondrial dynamic markers in Amyloid β (Aβ)-injected rats. Recognition aspect of memory and level of proteins were measured using novel object recognition test and Western blot, respectively. Our data indicated that even though flavone 1 was more effective than flavone 2 to prevent memory impairment, feeding with both flavones alleviated memory in Aβ-injected rats. Furthermore, in flavones-administered rats, mitochondrial dynamic balancing returned to the control level by the decline in Dynamin-related protei...

ACS Chemical Neuroscience, 2017

Two mechanisms underlie the inhibitory/acceleratory action of chemical compounds on tau aggregati... more Two mechanisms underlie the inhibitory/acceleratory action of chemical compounds on tau aggregation including the regulation of cellular kinases and phosphatases activity and direct binding to tau protein. Vitamin B12 is one of the tau polymerization inhibitors that its deficiency is linked to inactivation of protein phosphatase 2A and subsequently hyper phosphorylation and aggregation of tau protein. Regarding to the structure and function of vitamin B12 and tau protein we assumed that vitamin B12 is also able to directly bind to tau protein. Hence we investigated into the interaction of vitamin B12 with tau protein in vitro using fluorometry and circular dichrosim. Interaction studies was followed by investigation into the effect of vitamin B12 on tau aggregation using ThT fluorescence, Circular dichroism, transmission electron microscopy and SDS-PAGE. The results indicated that vitamin B12 interacts with tau protein and prevents fibrillization of tau protein. Blocking the cysteine residues of tau confirmed the cysteine-mediated binding of vitamin B12 to tau and showed that binding to cysteine is essential for inhibitory effect of vitamin B12 on tau aggregation. SDS-PAGE analysis indicated that vitamin B12 inhibits tau aggregation and tau oligomers formed in the presence of vitamin B12 are mostly SDS-soluble. We propose that direct binding of vitamin B12 is another mechanism underlying the inhibitory role of vitamin B12 on tau aggregation and neurodegeneration.

Acta virologica, 2008

DNA vaccination using a plasmid encoding Human rotavirus A (HuRV-A) inner capsid VP2 was examined... more DNA vaccination using a plasmid encoding Human rotavirus A (HuRV-A) inner capsid VP2 was examined in a mouse model. BALB/c mice were immunized intranasally (i.n.) with a VP2 DNA vaccine that induced cellular and humoral immune response to HuRV-A. The increased levels of cytokines IFN-gamma and IL-4 and the production of anti-VP2 IgG antibodies were detected. In addition, splenocyte proliferation detected by MTT test was enhanced in the mice treated with the vaccine. These results may encourage the development of a HuRV-A DNA vaccine derived from the inner layer of viral capsid that can be administered i.n.

Nanotechnology, 2005

Abstract TiO2 nanofibres were prepared using a templating method with tetraisopropylorthotitanate... more Abstract TiO2 nanofibres were prepared using a templating method with tetraisopropylorthotitanate (TiPT) as a precursor. The preparation comprises liquid phase deposition on cellulose fibres followed by thermal removal of the cellulose template. The obtained TiO2 fibrous substance consists of micron-size fibres with a microstructure of nanofibres. It was demonstrated that nanofibres are basically formed through the aggregation of TiO2 nanoparticles and nanorods into chain structures during the thermal ...

Journal of the Iranian Chemical Society, 2013

ABSTRACT Nowadays exposure to extremely low fre-quency electromagnetic fields (ELF-EMFs) is an un... more ABSTRACT Nowadays exposure to extremely low fre-quency electromagnetic fields (ELF-EMFs) is an unavoidable fact in human societies. In spite of destruc-tive effects of ELF-EMF such as impression on short-term memory and cognitive performances, neuroprotective and neurogeneration effects of ELF-EMF have been reported. On the other hand, microtubule (MT) proteins, the dynamic cytoskeleton proteins that are mostly located in axons, are able to produce local EMFs and possess key role in memory formation and consciousness. Therefore, MTs have strong potential to be affected by exogenous ELF-EMFs. In the present study, decline of MT poly-merization was shown by transmission electron micros-copy images and turbidimetry method after exposure to ELF-EMFs with 50, 100, and 217 Hz frequencies at 0.2 mT intensity. Circular dichroism and 8-anilino-1-naph-thalenesulfonate (ANS) fluorometry were used to dem-onstrate the MT secondary and third structural changes. Decrement of MT polymerization through disruption of tubulin native structure, and increasing the b-sheets and random coils were observed in all exposure conditions. Therefore, ELF-EMFs with 50, 100, and specially 217 Hz frequencies at 0.2 mT could lead to disruption of MT functions in the neural cells.

Chemical Biology & Drug Design, 2013

Doxorubicin-loaded chitosan-coated superparamagnetic iron oxide nanoparticles (Fe 3 O 4 ; SPIO-NP... more Doxorubicin-loaded chitosan-coated superparamagnetic iron oxide nanoparticles (Fe 3 O 4 ; SPIO-NPs) were prepared by coprecipitation and emulsification crosslinking method and uniform NPs with an average particle size of 82 nm, with high encapsulation efficiencies, were obtained. The drug-loading efficiency of doxorubicin (3.2 mg/mg NPs) showed better results for the chitosan-loaded SPIO-NPs as compared to the bare ones (0.5 mg/mg; p < 0.05). The incubation of A2780 and OVCAR-3 human ovarian cancer cells with doxorubicin-loaded and doxorubicin-loaded chitosan-coated SPIO-NPs, for 24, 48, 72, 96, and 120 h, showed significant IC 50 (2.0 AE 0.6 and 7.1 AE 2.7 mM doxorubicin) and IC 90 (4.0 AE 9.2 and 10 AE 0.5 mM doxorubicin), respectively, after 96 h of incubation. While, 95% and 98% growth inhibition was seen in A2780 and OVCAR-3 cells after the 96-h exposure to the doxorubicinchitosan-SPIO-NPs (p < 0.05). A 5-day (120 h) incubation with doxorubicin-chitosan-SPIO-NPs showed that A2780 and OVCAR-3 cells were able to uptake 120 and 110 pg iron/cell, respectively, when treated with doxorubicin-chitosan-SPIO-NPs for 72 h (p < 0.05).

Cells, 2021

A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compellin... more A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compelling evidence indicates that the presence of tau aggregates causes irreversible neuronal destruction, eventually leading to synaptic loss. So far, the inhibition of tau aggregation has been recognized as one of the most effective therapeutic strategies. Cannabidiol (CBD), a major component found in Cannabis sativa L., has antioxidant activities as well as numerous neuroprotective features. Therefore, we hypothesize that CBD may serve as a potent substance to hamper tau aggregation in AD. In this study, we aim to investigate the CBD effect on the aggregation of recombinant human tau protein 1N/4R isoform using biochemical methods in vitro and in silico. Using Thioflavin T (ThT) assay, circular dichroism (CD), and atomic force microscopy (AFM), we demonstrated that CBD can suppress tau fibrils formation. Moreover, by quenching assay, docking, and job’s plot, we further demonstrated that one m...

Biochimie, 2021

Telomerase activity is critical for cancer cells to provide unrestricted proliferation and cellul... more Telomerase activity is critical for cancer cells to provide unrestricted proliferation and cellular immortality through maintaining telomeres. Telomerase enzymatic activity is regulatable at the level of DNA, mRNA, post translational modifications, cellular transport and enzyme assembly. More recent studies confirm the interaction of the telomerase with various intracellular signaling pathways including PI3K/AKT/mTOR, NF-κB and Wnt/β-catenin which mainly participating in inflammation, epithelial to mesenchymal transition (EMT) and tumor cell invasion and metastasis. Furthermore, hTERT protein has been detected in non-nuclear sites such as the mitochondria and cytoplasm in cells. Mitochondrial TERT indicates various non-telomere-related functions such as decreasing reactive oxygen species (ROS) generation, boosting the respiration rate, protecting mtDNA by direct binding, interacting with mitochondrial tRNAs and increasing mitochondrial membrane potential which can lead to higher chemoresistance rate in cancer cells during therapies. Understanding the molecular mechanisms of the TERT function and depended interactions in tumor cells can suggest novel therapeutic approaches. Hence, in this review we will explain the telomerase activity regulation in translational and post translational levels besides the established correlations with various cell signaling pathways with possible pathways for therapeutic targeting.

Evidence-Based Complementary and Alternative Medicine, 2021

Medicinal plants have long been studied due to their anticancer effects and use of them is common... more Medicinal plants have long been studied due to their anticancer effects and use of them is commonly increased as a complementary and alternative medicine (CAM therapies) among patients with cancer. In this study, Alhagi maurorum (A.m) and Amygdalus haussknechtii (A.h) extracts were evaluated for their effects on inhibiting the growth of 4T1 breast cancer cells. Based on MTT assay results, the IC50s of A.m and A.h extracts were 57 µg/ml and 85 µg/ml, respectively. Then the cell migration, gene expression, and degree of apoptosis after 48 hours in each treated group with A.m and A.h extracts alone or in combination with docetaxel (DTX) on 4T1 cells were evaluated. A.m had a synergistic behavior with DTX (CI 1. Cell migration assay showed that each extract alone or in combination with DTX prevented the migration of 4T1 cells. The Ao/EB staining and flowcytometry results confirmed that, in combination therapy, A.m + DTX and A.h + DTX induced apoptosis close to the level of DTX. Real-ti...

Iranian biomedical journal, 2007

BACKGROUND Microtubules (MT) are important components of cell cytoskeleton and play key roles in ... more BACKGROUND Microtubules (MT) are important components of cell cytoskeleton and play key roles in cell motility mitosis and meiosis. They are also the targets of several anticancer agents which indicating their importance in maintaining cell viability. Microtubular reorganization contributing to apoptotic morphology occurs in normal and neoplastic cells undergoing apoptosis induced by cytotoxic drugs. The aim of this study was to correlate the changes in the MT with behavior of the gamma-tubulin in apoptotic cell, and to see if apoptitic MT showed biochemical characteristics of stable MT. METHODS Apoptosis was induced in the human leukemia cells (HL-60) by treatment with 1 microM of all-trans retinoic acid over a 5-day period. The time course of changes was assessed using flow cytometry, DNA fragmentation and immunocytochemistry in cells labeled for alpha-tubulins, acetylated alpha-tubulin and gamma-tubulin. RESULTS The results indicated that gamma-tubulin content is increased after ...

Cells

A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compellin... more A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compelling evidence indicates that the presence of tau aggregates causes irreversible neuronal destruction, eventually leading to synaptic loss. So far, the inhibition of tau aggregation has been recognized as one of the most effective therapeutic strategies. Cannabidiol (CBD), a major component found in Cannabis sativa L., has antioxidant activities as well as numerous neuroprotective features. Therefore, we hypothesize that CBD may serve as a potent substance to hamper tau aggregation in AD. In this study, we aim to investigate the CBD effect on the aggregation of recombinant human tau protein 1N/4R isoform using biochemical methods in vitro and in silico. Using Thioflavin T (ThT) assay, circular dichroism (CD), and atomic force microscopy (AFM), we demonstrated that CBD can suppress tau fibrils formation. Moreover, by quenching assay, docking, and job’s plot, we further demonstrated that one m...

European Journal of Human Genetics, 2019

PRPF31 is ubiquitously expressed splicing factor and has an essential role in the pre-mRNA splici... more PRPF31 is ubiquitously expressed splicing factor and has an essential role in the pre-mRNA splicing in all tissues. However, it is not clear how reduced expression of this general splicing factor leads to retinal restricted disease, retinitis pigmentosa (RP). In this study, we used RNA interference and RNA-sequencing to mimic the PRPF31 haploinsufficiency in human organotypic retinal cultures (HORCs). We examined the effects of PRPF31 deficiency on splicing by analyzing the differential exon usages (DEUs) and intron retentions of the retinal transcriptome. Our results revealed that the PRPF31 deficiency causes mis-splicing of genes involved in RNA processing (PRPF3, PRPF8, PRPF4, and PRPF19) and phototransduction (RHO, ROM1, FSCN2, GNAT2, and GNAT1) in the retina in the PRPF31 reduced samples. Mis-splicing of genes implicated in phototransduction was associated with photoreceptor degeneration observed in RP patients. Our data revealed that PRPF31 deficiency leads to the mis-splicing of a distinct subset of pre-mRNAs with a widespread effect on phototransduction and RNA processing.

ACS Biomaterials Science & Engineering, 2019

Molecular Biology Reports, 2019

Cisplatin is widely used as an anticancer drug in chemotherapy of human cancers. In the field of ... more Cisplatin is widely used as an anticancer drug in chemotherapy of human cancers. In the field of cancer therapy, nanoparticles modified with biocompatible copolymers are suitable vehicles to effectively deliver smaller doses of hydrophobic drugs such as cisplatin in the body. In this study, we investigated whether cisplatin-loaded iron oxide nanoparticles (IONPs) modified with chitosan can exert cytotoxic effects in the human breast cancer cell line MDA-MB-231. IONPs was synthesized using eucalyptus leaf extract as a reducing and stabilizing agent. MDA-MB-231 cells were treated with different concentrations of cisplatin, cisplatin-IONPs and cisplatin-IONPs-chitosan for 24 h. Apoptosis was confirmed by flow cytometry, whereas The mRNA and protein expression of pro-and anti-apoptotic molecules were measured using Real time RT-PCR and western blotting. Treatment with both cisplatin-IONPs and cisplatin-IONPs-chitosan showed a significantly higher cytotoxic effect in comparison to the free drug alone in MDA-MB-231 cells. The levels of apoptosis in cells treated with a combination of cisplatin-IONPs-chitosan were significantly higher compared with cisplatin-IONPs and cisplatin alone. The results of this study showed that the interaction between cisplatin and iron oxide nanoparticles modified with chitosan could enhance responsiveness to cisplatin in breast cancer cells.

European journal of pharmacology, Jan 5, 2018

Reactive oxygen species (ROS) are essential mediators of crucial cellular processes including apo... more Reactive oxygen species (ROS) are essential mediators of crucial cellular processes including apoptosis, proliferation, survival and cell cycle. Their regulatory role in cancer progression has seen in different human malignancies such as acute myeloid leukemia (AML). AML patients suffer from high resistance of the tumors against routine therapeutics including ATO. ATO enhance reactive oxygen species levels and induce apoptosis and suppresses proliferation in AML cells. However, some pathways such as JAK2/STAT3 ease anti-tumor activity of ATO by reducing reactive oxygen species amount and protecting the cell from apoptosis. In the present study, we use ruxolitinib (potent JAK2 inhibitor) to increase the sensitivity of AML cells to ATO treatment. We test, the effect of this combination on metabolic activity, proliferation, colony formation, cell cycle distribution, apoptosis, oxidative stress and DNA damage. Our results showed that combination of ATO with ruxolitinib synergistically r...

International journal of biological macromolecules, 2018

Ozone has been known for several decades, with its antiseptic and therapeutic effects determined ... more Ozone has been known for several decades, with its antiseptic and therapeutic effects determined by the hormesis theory. It is shown that the therapeutic efficacy of ozone therapy may be partly due to the controlled and moderate oxidative stress produced by the reaction of ozone with several biological components. In this study, the effect of ozone on healthy human hemoglobin (Hb) in the whole blood environment (in the presence of antioxidants) and in the purified form (in the absence of antioxidants) is investigated using a number of different techniques including intrinsic fluorescence, circular dichroism and UV-VIS absorption spectroscopy as well as SDS- and Native-PAGE and dynamic light scattering. The results show that the presence of antioxidants prevents damage to Hb while its absence means that as the exposure to ozone is increased, Hb is increasingly damaged. These results highlight the importance for the use of appropriate doses of ozone, for patients with different diseas...

PloS one, 2018

This study investigated for the first time the molecular effectiveness of 'aroma' from th... more This study investigated for the first time the molecular effectiveness of 'aroma' from three small molecules including a phenol (phenyl ethyl alcohol; PEA) and an aldehyde (cinnamaldehyde; Cin) both containing an aromatic ring, and a diamine (N,N,N,N'- Tetramethylethylenediamine; TEMED) at two different amounts (small; S and large; L) in preventing hen egg white lysozyme (HEWL) amyloid fibril formation using Thioflavin T and Nile red fluorescence assays, circular dichroism spectroscopy, SDS-polyacrylamide gel electrophoresis, atomic force microscopy, dynamic light scattering and HEWL activity test. Interestingly, the results revealed that (1) the aroma of PEA, identified as an active constituent of Rosa damascena, prevented fibril formation since PEA-L was able to trap the oligomeric form of HEWL in contrast to PEA-S where protofibrils but not mature fibrils were formed; (2) Cin, previously shown to prevent fibril formation in the liquid form, was also shown to do so in ...

European journal of pharmacology, Jan 5, 2018

Glioblastoma multiform (GBM) accounts for the most common form of primary brain tumors with very ... more Glioblastoma multiform (GBM) accounts for the most common form of primary brain tumors with very limited survival rate. Drug resistance is the main challenges for good prognosis of GBM patients. Arsenic trioxide (ATO) as a multifunctional drug has been investigated for the treatment of several solid tumors. Amplification/overexpression of the epidermal growth factor receptor (EGFR) gene as a signature genetic abnormality of GBM tumors can be a chemoresistance mechanism. In this study, we use erlotinib as an EGFR inhibitor to increase the sensitivity of GBM cell lines to ATO treatment. We evaluate the effects of this combination on metabolic activity, viability, cell proliferation, colony formation, cell cycle distribution, migration, oxidative stress and reactive oxygen species production. Our results showed that combination of ATO with erlotinib synergistically reduced metabolic activity, proliferation and colony forming potential in treated GBM cell lines. This combination induced...

Annals of hematology, Jan 20, 2017

PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation i... more PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4. Analysis of promoter methylation status of 22 cell cycle related genes in NB4 revealed that CCND1, CCNE1, CCNF, CDKN1A, GADD45α, and RBL1 genes were methylated 60.7, 84.6, 58.6, 8.7, 33.4, and 73.7%, respectively, that after treatment with 2 μM ATO for 48 h, turn into 0.6, 13.8, 0.1, 6.6, 10.7, and 54.5% methy...

Nutritional neuroscience, Jan 9, 2017

Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treat... more Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treatment of chronic conditions, including cancer and neurodegenerative disorders. Accordingly, in the present study, we aimed at evaluating the effects of oral intake of two structurally different flavonoids 5-hydroxy-6,7,4'-trimethoxyflavone (flavone 1) and 5,7,4'-trihydroxyflavone (flavone 2) on recognition memory, hippocampal protein level of immediate early gene cFos and mitochondrial dynamic markers in Amyloid β (Aβ)-injected rats. Recognition aspect of memory and level of proteins were measured using novel object recognition test and Western blot, respectively. Our data indicated that even though flavone 1 was more effective than flavone 2 to prevent memory impairment, feeding with both flavones alleviated memory in Aβ-injected rats. Furthermore, in flavones-administered rats, mitochondrial dynamic balancing returned to the control level by the decline in Dynamin-related protei...

ACS Chemical Neuroscience, 2017

Two mechanisms underlie the inhibitory/acceleratory action of chemical compounds on tau aggregati... more Two mechanisms underlie the inhibitory/acceleratory action of chemical compounds on tau aggregation including the regulation of cellular kinases and phosphatases activity and direct binding to tau protein. Vitamin B12 is one of the tau polymerization inhibitors that its deficiency is linked to inactivation of protein phosphatase 2A and subsequently hyper phosphorylation and aggregation of tau protein. Regarding to the structure and function of vitamin B12 and tau protein we assumed that vitamin B12 is also able to directly bind to tau protein. Hence we investigated into the interaction of vitamin B12 with tau protein in vitro using fluorometry and circular dichrosim. Interaction studies was followed by investigation into the effect of vitamin B12 on tau aggregation using ThT fluorescence, Circular dichroism, transmission electron microscopy and SDS-PAGE. The results indicated that vitamin B12 interacts with tau protein and prevents fibrillization of tau protein. Blocking the cysteine residues of tau confirmed the cysteine-mediated binding of vitamin B12 to tau and showed that binding to cysteine is essential for inhibitory effect of vitamin B12 on tau aggregation. SDS-PAGE analysis indicated that vitamin B12 inhibits tau aggregation and tau oligomers formed in the presence of vitamin B12 are mostly SDS-soluble. We propose that direct binding of vitamin B12 is another mechanism underlying the inhibitory role of vitamin B12 on tau aggregation and neurodegeneration.

Acta virologica, 2008

DNA vaccination using a plasmid encoding Human rotavirus A (HuRV-A) inner capsid VP2 was examined... more DNA vaccination using a plasmid encoding Human rotavirus A (HuRV-A) inner capsid VP2 was examined in a mouse model. BALB/c mice were immunized intranasally (i.n.) with a VP2 DNA vaccine that induced cellular and humoral immune response to HuRV-A. The increased levels of cytokines IFN-gamma and IL-4 and the production of anti-VP2 IgG antibodies were detected. In addition, splenocyte proliferation detected by MTT test was enhanced in the mice treated with the vaccine. These results may encourage the development of a HuRV-A DNA vaccine derived from the inner layer of viral capsid that can be administered i.n.

Nanotechnology, 2005

Abstract TiO2 nanofibres were prepared using a templating method with tetraisopropylorthotitanate... more Abstract TiO2 nanofibres were prepared using a templating method with tetraisopropylorthotitanate (TiPT) as a precursor. The preparation comprises liquid phase deposition on cellulose fibres followed by thermal removal of the cellulose template. The obtained TiO2 fibrous substance consists of micron-size fibres with a microstructure of nanofibres. It was demonstrated that nanofibres are basically formed through the aggregation of TiO2 nanoparticles and nanorods into chain structures during the thermal ...

Journal of the Iranian Chemical Society, 2013

ABSTRACT Nowadays exposure to extremely low fre-quency electromagnetic fields (ELF-EMFs) is an un... more ABSTRACT Nowadays exposure to extremely low fre-quency electromagnetic fields (ELF-EMFs) is an unavoidable fact in human societies. In spite of destruc-tive effects of ELF-EMF such as impression on short-term memory and cognitive performances, neuroprotective and neurogeneration effects of ELF-EMF have been reported. On the other hand, microtubule (MT) proteins, the dynamic cytoskeleton proteins that are mostly located in axons, are able to produce local EMFs and possess key role in memory formation and consciousness. Therefore, MTs have strong potential to be affected by exogenous ELF-EMFs. In the present study, decline of MT poly-merization was shown by transmission electron micros-copy images and turbidimetry method after exposure to ELF-EMFs with 50, 100, and 217 Hz frequencies at 0.2 mT intensity. Circular dichroism and 8-anilino-1-naph-thalenesulfonate (ANS) fluorometry were used to dem-onstrate the MT secondary and third structural changes. Decrement of MT polymerization through disruption of tubulin native structure, and increasing the b-sheets and random coils were observed in all exposure conditions. Therefore, ELF-EMFs with 50, 100, and specially 217 Hz frequencies at 0.2 mT could lead to disruption of MT functions in the neural cells.

Chemical Biology & Drug Design, 2013

Doxorubicin-loaded chitosan-coated superparamagnetic iron oxide nanoparticles (Fe 3 O 4 ; SPIO-NP... more Doxorubicin-loaded chitosan-coated superparamagnetic iron oxide nanoparticles (Fe 3 O 4 ; SPIO-NPs) were prepared by coprecipitation and emulsification crosslinking method and uniform NPs with an average particle size of 82 nm, with high encapsulation efficiencies, were obtained. The drug-loading efficiency of doxorubicin (3.2 mg/mg NPs) showed better results for the chitosan-loaded SPIO-NPs as compared to the bare ones (0.5 mg/mg; p < 0.05). The incubation of A2780 and OVCAR-3 human ovarian cancer cells with doxorubicin-loaded and doxorubicin-loaded chitosan-coated SPIO-NPs, for 24, 48, 72, 96, and 120 h, showed significant IC 50 (2.0 AE 0.6 and 7.1 AE 2.7 mM doxorubicin) and IC 90 (4.0 AE 9.2 and 10 AE 0.5 mM doxorubicin), respectively, after 96 h of incubation. While, 95% and 98% growth inhibition was seen in A2780 and OVCAR-3 cells after the 96-h exposure to the doxorubicinchitosan-SPIO-NPs (p < 0.05). A 5-day (120 h) incubation with doxorubicin-chitosan-SPIO-NPs showed that A2780 and OVCAR-3 cells were able to uptake 120 and 110 pg iron/cell, respectively, when treated with doxorubicin-chitosan-SPIO-NPs for 72 h (p < 0.05).

Cells, 2021

A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compellin... more A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compelling evidence indicates that the presence of tau aggregates causes irreversible neuronal destruction, eventually leading to synaptic loss. So far, the inhibition of tau aggregation has been recognized as one of the most effective therapeutic strategies. Cannabidiol (CBD), a major component found in Cannabis sativa L., has antioxidant activities as well as numerous neuroprotective features. Therefore, we hypothesize that CBD may serve as a potent substance to hamper tau aggregation in AD. In this study, we aim to investigate the CBD effect on the aggregation of recombinant human tau protein 1N/4R isoform using biochemical methods in vitro and in silico. Using Thioflavin T (ThT) assay, circular dichroism (CD), and atomic force microscopy (AFM), we demonstrated that CBD can suppress tau fibrils formation. Moreover, by quenching assay, docking, and job’s plot, we further demonstrated that one m...

Biochimie, 2021

Telomerase activity is critical for cancer cells to provide unrestricted proliferation and cellul... more Telomerase activity is critical for cancer cells to provide unrestricted proliferation and cellular immortality through maintaining telomeres. Telomerase enzymatic activity is regulatable at the level of DNA, mRNA, post translational modifications, cellular transport and enzyme assembly. More recent studies confirm the interaction of the telomerase with various intracellular signaling pathways including PI3K/AKT/mTOR, NF-κB and Wnt/β-catenin which mainly participating in inflammation, epithelial to mesenchymal transition (EMT) and tumor cell invasion and metastasis. Furthermore, hTERT protein has been detected in non-nuclear sites such as the mitochondria and cytoplasm in cells. Mitochondrial TERT indicates various non-telomere-related functions such as decreasing reactive oxygen species (ROS) generation, boosting the respiration rate, protecting mtDNA by direct binding, interacting with mitochondrial tRNAs and increasing mitochondrial membrane potential which can lead to higher chemoresistance rate in cancer cells during therapies. Understanding the molecular mechanisms of the TERT function and depended interactions in tumor cells can suggest novel therapeutic approaches. Hence, in this review we will explain the telomerase activity regulation in translational and post translational levels besides the established correlations with various cell signaling pathways with possible pathways for therapeutic targeting.

Evidence-Based Complementary and Alternative Medicine, 2021

Medicinal plants have long been studied due to their anticancer effects and use of them is common... more Medicinal plants have long been studied due to their anticancer effects and use of them is commonly increased as a complementary and alternative medicine (CAM therapies) among patients with cancer. In this study, Alhagi maurorum (A.m) and Amygdalus haussknechtii (A.h) extracts were evaluated for their effects on inhibiting the growth of 4T1 breast cancer cells. Based on MTT assay results, the IC50s of A.m and A.h extracts were 57 µg/ml and 85 µg/ml, respectively. Then the cell migration, gene expression, and degree of apoptosis after 48 hours in each treated group with A.m and A.h extracts alone or in combination with docetaxel (DTX) on 4T1 cells were evaluated. A.m had a synergistic behavior with DTX (CI 1. Cell migration assay showed that each extract alone or in combination with DTX prevented the migration of 4T1 cells. The Ao/EB staining and flowcytometry results confirmed that, in combination therapy, A.m + DTX and A.h + DTX induced apoptosis close to the level of DTX. Real-ti...

Iranian biomedical journal, 2007

BACKGROUND Microtubules (MT) are important components of cell cytoskeleton and play key roles in ... more BACKGROUND Microtubules (MT) are important components of cell cytoskeleton and play key roles in cell motility mitosis and meiosis. They are also the targets of several anticancer agents which indicating their importance in maintaining cell viability. Microtubular reorganization contributing to apoptotic morphology occurs in normal and neoplastic cells undergoing apoptosis induced by cytotoxic drugs. The aim of this study was to correlate the changes in the MT with behavior of the gamma-tubulin in apoptotic cell, and to see if apoptitic MT showed biochemical characteristics of stable MT. METHODS Apoptosis was induced in the human leukemia cells (HL-60) by treatment with 1 microM of all-trans retinoic acid over a 5-day period. The time course of changes was assessed using flow cytometry, DNA fragmentation and immunocytochemistry in cells labeled for alpha-tubulins, acetylated alpha-tubulin and gamma-tubulin. RESULTS The results indicated that gamma-tubulin content is increased after ...

Cells

A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compellin... more A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compelling evidence indicates that the presence of tau aggregates causes irreversible neuronal destruction, eventually leading to synaptic loss. So far, the inhibition of tau aggregation has been recognized as one of the most effective therapeutic strategies. Cannabidiol (CBD), a major component found in Cannabis sativa L., has antioxidant activities as well as numerous neuroprotective features. Therefore, we hypothesize that CBD may serve as a potent substance to hamper tau aggregation in AD. In this study, we aim to investigate the CBD effect on the aggregation of recombinant human tau protein 1N/4R isoform using biochemical methods in vitro and in silico. Using Thioflavin T (ThT) assay, circular dichroism (CD), and atomic force microscopy (AFM), we demonstrated that CBD can suppress tau fibrils formation. Moreover, by quenching assay, docking, and job’s plot, we further demonstrated that one m...