Ali Zekri - Academia.edu (original) (raw)

Papers by Ali Zekri

Anti-Cancer Drugs, Sep 1, 2017

Aurora-B kinase overexpression plays important roles in the malignant progression of prostate can... more Aurora-B kinase overexpression plays important roles in the malignant progression of prostate cancer (PCa). AZD1152-HQPA, as an inhibitor of Aurora-B, has recently emerged as a promising agent for cancer treatment. In this study, we aimed to investigate the effects of AZD1152-HQPA on reactive oxygen species (ROS) generation and mitochondrial function in PCa. We used AZD1152-HQPA (Barasertib), a highly potent and selective inhibitor of Aurora-B kinase. The effects of AZD1152-HQPA on cell viability, DNA content, cell morphology, and ROS production were studied in the androgen-independent PC-3 PCa cell line. Moreover, the mitochondrial copy number and the expression of genes involved in cell survival and cancer stem cell maintenance were investigated. We found that AZD1152-HQPA treatment induced defective cell survival, polyploidy, micronuclei formation, cell enlargement, and cell death by significant overexpression of p73, p21 and downregulation of cell cycle-regulatory genes in a drug concentration-dependent manner. Moreover, AZD1152 treatment led to an excessive ROS generation and an increase in the mitochondrial copy number not only in PC-3 but also in several other malignant cells. AZD1152 treatment also led to downregulation of genes involved in the maintenance of cancer stem cells. Our results showed a functional relationship between the aurora kinase inhibition, an increase in mitochondrial copy number, and ROS generation in therapeutic modalities of cancer. This study suggests that the excessive ROS generation may be a novel mechanism of cytotoxicity induced by the aurora kinase inhibitor, AZD1152-HQPA.

Medical Science Journal of Islamic Azad …, 2011

Page 1. ﻣ ﻪﻠﺠ مﻮﻠﻋ ﻲﻜﺷﺰﭘ ﻲﻣﻼﺳا دازآ هﺎﮕﺸﻧاد دهرو 21 هرﺎﻤﺷ ، 2 ، نﺎﺘﺴﺑﺎﺗ 90 ، تﺎﺤﻔﺻ 71 ﺎﺗ81 ﺶﻘﻧ هد... more Page 1. ﻣ ﻪﻠﺠ مﻮﻠﻋ ﻲﻜﺷﺰﭘ ﻲﻣﻼﺳا دازآ هﺎﮕﺸﻧاد دهرو 21 هرﺎﻤﺷ ، 2 ، نﺎﺘﺴﺑﺎﺗ 90 ، تﺎﺤﻔﺻ 71 ﺎﺗ81 ﺶﻘﻧ هداﻮﻧﺎﺧ يﺎﻫزﺎﻨﻴﻛ ارورآ (Aurora Kinases) رد لﻮﻠﺳ ﻢﻴﺴﻘﺗ و نﺎﻃﺮﺳ نﺎﻣرد ﻲﻳﻮﻟد يرﻮﻧ ﺎﺿر ﺪﻤﺤﻣ 1، يﺮﻛذ ﻲﻠﻋ 2 1 ،ﻲﻜﺷﺰﭘ ﻲﻟﻮﻜﻟﻮﻣ ﻚﻴﺘﻧژ دﺎﺘﺳا ،ﻲﻜﺷﺰﭘ ﻚﻴﺘﻧژ هوﺮﮔ ﻲﻜﺷﺰﭘ هﺪﻜﺸﻧاد ، اد ناﺮﻬﺗ ﻲﻜﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧ ...

Clinical and Experimental Dermatology

PLACK syndrome is a relatively recently defined generalized Peeling Skin Syndrome (PSS) that has ... more PLACK syndrome is a relatively recently defined generalized Peeling Skin Syndrome (PSS) that has been reported with major skin manifestations and sometimes atypical features. Herein, the case of a five-year-old boy with PLACK manifestations is reported. Whole exome sequencing and subsequent Sanger sequencing identified a putative splice variant c.1209 + 2T > G in CAST (NM_001042440.5). Moreover, mRNA sequencing confirmed the abnormal alternative splicing of the CAST gene leading to the addition of one nucleotide to the correct open reading frame at the mRNA level. Segregation and expression analysis revealed that this loss-of-function via mRNA nonsense-mediated decay could be the causative pathogenic mechanism responsible for the patient’s phenotype. This study extends our understanding of the various phenotypic and genotypic features of PLACK disease.

Cancer Microenvironment, 2015

Presence of tumor initiating cells and a proper niche is essential for metastatic colonization. S... more Presence of tumor initiating cells and a proper niche is essential for metastatic colonization. SLUG and SOX9 transcription factors play essential roles in induction and maintenance of tumor initiating capacity in breast cancer cells. On the other hand, Tenascin-C and Periostin are crucial factors in metastatic niche that support tumor initiating capability in breast cancer. In this study, regulatory effect of SLUG and SOX9 transcription factors on the expression of Tenascin-C and Periostin was examined. SLUG and SOX9 were overexpressed and knocked-down in MCF7 and MDA-MB-231 cells, respectively. The cells as little and highly invasive breast cancerderived cells were infected by inducing and shRNA lentivirus constructs. Then, Tenascin-C and Periostin as well as SLUG and SOX9 expression levels were measured in the cells via Real-Time PCR. Simultaneous overexpression of SLUG and SOX9 significantly induced Tenascin-C and Periostin expression. SLUG and SOX9 knock-down also significantly reduced the expression of Tenascin-C and Periostin. In this analysis Periostin showed the most deviation in both up-and downregulation levels. This regulatory effect might shed light to a crosstalk between factors involved in the tumor initiating capacity and metastatic niche of the breast cancer.

Scientific Journal of Iran Blood Transfus Organ, 2013

Background and Objectives Arsenic trioxide (ATO) is an active drug in treatment of acute promyelo... more Background and Objectives Arsenic trioxide (ATO) is an active drug in treatment of acute promyelocytic leukemia (APL), but has adverse effects on patients. In order to enhance antileukemic effectiveness and to reduce dosage of ATO, combinatorial effect of it with Azidothymidine (AZT) in apoptosis induction was evaluated on APL cell line (NB4). Materials and Methods The cells cultured and treated with 50 μM AZT and/or ATO for 48 hrs and then with apoptosis, cell cycle distribution, and P21 mRNA levels in comparison with untreated cells (control) were analyzed by flow cytometry and Real Time PCR, respectively. Results ATO led to induction of apoptosis (50.14% ± 7.12) in comparison with the control (3.9% ± 2.97) through the increment of the cell cycle arrest in G2/M. The apoptotic effect of ATO had been inhibited in cells treated with combination of AZT/ATO (24.35% ± 4.65). This inhibition was associated with the relative reduction of the cells in G2/M and relative increase of the cell...

Archives of Iranian medicine, 2014

Silibinin is a traditionally well-known drug for its hepatoprotective efficacy against various ty... more Silibinin is a traditionally well-known drug for its hepatoprotective efficacy against various types of liver afflictions. In addition, it has recently been considered broadly as a potential chemopreventive agent against many types of cancers. The current study was designed to evaluate the restrictive effects of pharmacological doses of silibinin on SKBR3, an ErbB2-overexpressed and ER-negative human breast carcinoma cell line. Effect of silibinin on metabolic activity and proliferation of human breast carcinoma (SKBR3) cell line were evaluated by MTT and BrdU assays respectively. Furthermore, the proapoptotic effect of silibinin was investigated using flow cytometry. The NF-κB phosphorylation assay was also used to assess the effect of silibinin on NF-κB activation. The alkalizing effect of silibinin on SKBR3 cell line was evaluated by measuring pH of media of the silibinin-treated cells compared to control. Our results indicate that silibinin inhibited metabolic activity and cell ...

Background and Objective: Colorectal cancer (CRC) is the third most prevalent cancer in the world... more Background and Objective: Colorectal cancer (CRC) is the third most prevalent cancer in the world with high rates of mortality, which makes it of great importance to be efficiently cured. Aurora kinase family (including Aurora A, B, and C) regulate several phases of cell cycle in mammalian cells. Aurora-B is overexpressed in various types of solid tumors and leukemia, and in that case, the prognosis is poor. AZD1152 is a selective inhibitor for Aurora kinase B. The purpose of this study is to investigate the effects of AZD1152 and its mechanism of action on two CRC cell lines. Methods: In this experimental study, two cell lines including Caco-2 and HCT-116, were used as models of CRC. Trypsin was utilized for passaging the mentioned cell lines. AZD1152 was provided with primary concentration of 1000 μM and diluted to achieve specific concentrations. Antitumor properties of AZD1152 on cell lines were investigated using MTT (Microculture Tetrazolium Test) and clonogenic assays. Studen...

Reports of biochemistry & molecular biology, 2014

BACKGROUND The study of specific genes expressed in the testis is important to understanding test... more BACKGROUND The study of specific genes expressed in the testis is important to understanding testis development and function. Spermatogenesis is an attractive model for the study of gene expression during germ cell differentiation. Spermatogenesis associated-19 (Spata-19) is a recently-identified important spermatogenesis-related gene specifically expressed in testis. Its protein product is involved in sperm cell development and reproduction. In this report we examined the expression of Spata-19 mRNA in mouse testis, fetus, and cell lines. METHODS Reverse transcription-polymerase chain reaction (RT-PCR), nested PCR, and PCR-restriction fragment length polymorphism (PCR-RFLP) were used to analyze Spata-19 mRNA expression in different stages of mouse testis development, mouse fetus, mouse embryonic fibroblasts (MEF), mouse embryonic stem cells (mESC), Sertoli cells, and NIH/3T3 cells. RESULTS We identified a novel splice variant of Spata-19 in the mouse genome that it is expressed in ...

Frontiers in Anti-Cancer Drug Discovery, 2015

Multidisciplinary Cancer Investigation, Nov 1, 2017

Medical Journal of the Islamic Republic of Iran, 2020

Background: Epidermolysis bullosa simplex is a hereditary skin disorder caused by mutations in se... more Background: Epidermolysis bullosa simplex is a hereditary skin disorder caused by mutations in several genes such as KRT5 and KRT14 . Skin fragility in basal keratinocytes presence regions led to the cytolysis of epidermis and blistering. Aim of this study was to detect the molecular defects in KRT5 and KRT14 genes hot spots in patients with clinical suspicion of EBS and investigation of their probable genotype-phenotype correlations. Methods: Exons 1 and 6-7 of KRT5 and exons 1 and 4-7 of KRT14 amplification and mutation detection were performed by polymerase chain reaction and Sanger sequencing, respectively. Novel variants pathogenicity evaluated by bioinformatics tools. Results: Nine important variants detected in seven different patients within 6 Iranian families affected by Epidermolysis bullosa simplex, of which four variants were novel. Three patients had a mottled pigmentation phenotype [G96D (p.Gly96Asp) and F97I (p.Phe97Ile) in KRT5 ]. One of them showed a Dowling–Meara p...

Background and Objective: Colorectal cancer (CRC) is the third most prevalent cancer in the world... more Background and Objective: Colorectal cancer (CRC) is the third most prevalent cancer in the world with high rates of mortality, which makes it of great importance to be efficiently cured. Aurora kinase family (including Aurora A, B, and C) regulate several phases of cell cycle in mammalian cells. Aurora-B is overexpressed in various types of solid tumors and leukemia, and in that case, the prognosis is poor. AZD1152 is a selective inhibitor for Aurora kinase B. The purpose of this study is to investigate the effects of AZD1152 and its mechanism of action on two CRC cell lines. Methods: In this experimental study, two cell lines including Caco-2 and HCT-116, were used as models of CRC. Trypsin was utilized for passaging the mentioned cell lines. AZD1152 was provided with primary concentration of 1000 μM and diluted to achieve specific concentrations. Antitumor properties of AZD1152 on cell lines were investigated using MTT (Microculture Tetrazolium Test) and clonogenic assays. Studen...

International Journal of Molecular and Cellular Medicine, 2018

Waardenburg syndrome (WS) is a neurocristopathy with an autosomal dominant mode of inheritance, a... more Waardenburg syndrome (WS) is a neurocristopathy with an autosomal dominant mode of inheritance, and considerable clinical and genetic heterogeneity. WS type II is the most common type of WS in many populations presenting with sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eye, and pigmentary abnormalities of the hair and skin. To date, mutations of MITF, SOX10, and SNAI2 have been implicated in the pathogenesis of WS2. Although different pathogenic mutations have been reported in many ethnic groups, the data on Iranian WS2 patients is insufficient. 31 WS2 patients, including 22 men and 9 women from 14 families were included. Waardenburg consortium guidelines were employed for WS2 diagnosis. WS2 patients underwent screening for MITF, SOX10, and SNAI2 mutations using direct sequencing and MLPA analysis. Clinical evaluation revealed prominent phenotypic variability in Iranian WS2 patients. Sensorineural hearing impairment and heterochromia iridis were the most...

Archives of Iranian medicine, 2014

BACKGROUND Silibinin is a traditionally well-known drug for its hepatoprotective efficacy against... more BACKGROUND Silibinin is a traditionally well-known drug for its hepatoprotective efficacy against various types of liver afflictions. In addition, it has recently been considered broadly as a potential chemopreventive agent against many types of cancers. The current study was designed to evaluate the restrictive effects of pharmacological doses of silibinin on SKBR3, an ErbB2-overexpressed and ER-negative human breast carcinoma cell line. METHODS Effect of silibinin on metabolic activity and proliferation of human breast carcinoma (SKBR3) cell line were evaluated by MTT and BrdU assays respectively. Furthermore, the proapoptotic effect of silibinin was investigated using flow cytometry. The NF-κB phosphorylation assay was also used to assess the effect of silibinin on NF-κB activation. The alkalizing effect of silibinin on SKBR3 cell line was evaluated by measuring pH of media of the silibinin-treated cells compared to control. RESULTS Our results indicate that silibinin inhibited m...

Journal of pediatric nephrology, 2020

The novel coronavirus, known as a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), i... more The novel coronavirus, known as a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a single-stranded RNA virus, from which structural and some accessory proteins are encoded. It seems that this newly emerged virus uses the ACE2 receptor to enter the cells in the human body. SARS-CoV-2 undergoes an intense immunological pressure in humans, and this generates mutations to bypass the immune system. Some mutations have been detected in this virus genome, which can induce a change in viral potency. By performing pathway enrichment analysis over those genes and identifying relevant protein-protein interactions (PPIs), we were able to list essential pathways affected in infected cells. In this review, we mainly discuss genetic, intracellular mechanisms, diagnosis and feasible therapeutic targets of this novel coronavirus.

Efforts to discover new anti-cancer drugs are limited by the fact that human and animal models fo... more Efforts to discover new anti-cancer drugs are limited by the fact that human and animal models for testing the effectiveness of drugs are not completely faithful for recapitulation of this complex disease. These models cancer have mainly consisted of cell lines derived from human tumors or Xenografts in mice and more recently, genetically engineered mouse models of human tumor. Cell lines offer an almost infinite supply of similar cells to the genotypes and phenotypes of original tumors. Application of cell lines help scientist to cope with the ethical issues and also resolve the challenge of discrepancy associated with animal studies and human clinical trials.

Frontiers in Oncology

Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a ... more Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a prominent impact in the pathogenesis of breast cancer. Among the transcription factors associated with ESR signaling, FOXM1, GATA3, FOXA1 and ESR1 have been suggested as a candidate in the pathogenesis of this neoplasm. In the current project, we have designed an in silico approach to find long non-coding RNAs (lncRNAs) that regulate these transcription factors. Then, we used clinical samples to carry out validation of our in silico findings. Our systems biology method led to the identification of APTR, AC144450.1, linc00663, ZNF337.AS1, and RAMP2.AS1 lncRNAs. Subsequently, we assessed the expression of these genes in breast cancer tissues compared with the adjacent non-cancerous tissues (ANCTs). Expression of GATA3 was significantly higher in breast cancer tissues compared with ANCTs (Ratio of mean expressions (RME) = 4.99, P value = 3.12E−04). Moreover, expression levels of APTR, AC144...

Acta Physiologica Hungarica, 2014

ABSTRACT Endoplasmic reticulum (ER) stress provides abnormalities in insulin action, inflammatory... more ABSTRACT Endoplasmic reticulum (ER) stress provides abnormalities in insulin action, inflammatory responses, lipoprotein B100 degradation and hepatic lipogenesis. Excess accumulation of triglyceride in hepatocytes may also lead to disorders such as non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Opioid peptides are involved in triglyceride and cholesterol dysregulation, inflammation and cell death. In this study, we evaluated Naltrexone effects on ER stress induced liver injury. To do so, C57/BL6 mice received saline, DMSO and Naltrexone, as control groups. ER stress was induced by tunicamycin (TM) injection. Naltrexone was given before TM administration. Liver blood flow and biochemical serum analysis were measured. Histopathological evaluations, TNF-α measurement and Real-time RT-PCR were also performed. TM challenge provokes steatosis, cellular ballooning and lobular inflammation which significantly reduced in Naltrexone treated animals. ALT, AST and TNF-α increased in the TM group and improved in the Naltrexone plus TM group. Triglyceride and cholesterol levels decreased in TM treated mice with no increase in Naltrexone treated animals. In the Naltrexone plus TM group, gene expression of Bax/Bcl-2 ratio and caspase3 significantly lowered compared with the TM group. In this study, we found that Naltrexone had a notable alleviating role in ER stress induced steatosis and liver injury.

Anti-Cancer Drugs, Sep 1, 2017

Aurora-B kinase overexpression plays important roles in the malignant progression of prostate can... more Aurora-B kinase overexpression plays important roles in the malignant progression of prostate cancer (PCa). AZD1152-HQPA, as an inhibitor of Aurora-B, has recently emerged as a promising agent for cancer treatment. In this study, we aimed to investigate the effects of AZD1152-HQPA on reactive oxygen species (ROS) generation and mitochondrial function in PCa. We used AZD1152-HQPA (Barasertib), a highly potent and selective inhibitor of Aurora-B kinase. The effects of AZD1152-HQPA on cell viability, DNA content, cell morphology, and ROS production were studied in the androgen-independent PC-3 PCa cell line. Moreover, the mitochondrial copy number and the expression of genes involved in cell survival and cancer stem cell maintenance were investigated. We found that AZD1152-HQPA treatment induced defective cell survival, polyploidy, micronuclei formation, cell enlargement, and cell death by significant overexpression of p73, p21 and downregulation of cell cycle-regulatory genes in a drug concentration-dependent manner. Moreover, AZD1152 treatment led to an excessive ROS generation and an increase in the mitochondrial copy number not only in PC-3 but also in several other malignant cells. AZD1152 treatment also led to downregulation of genes involved in the maintenance of cancer stem cells. Our results showed a functional relationship between the aurora kinase inhibition, an increase in mitochondrial copy number, and ROS generation in therapeutic modalities of cancer. This study suggests that the excessive ROS generation may be a novel mechanism of cytotoxicity induced by the aurora kinase inhibitor, AZD1152-HQPA.

Medical Science Journal of Islamic Azad …, 2011

Page 1. ﻣ ﻪﻠﺠ مﻮﻠﻋ ﻲﻜﺷﺰﭘ ﻲﻣﻼﺳا دازآ هﺎﮕﺸﻧاد دهرو 21 هرﺎﻤﺷ ، 2 ، نﺎﺘﺴﺑﺎﺗ 90 ، تﺎﺤﻔﺻ 71 ﺎﺗ81 ﺶﻘﻧ هد... more Page 1. ﻣ ﻪﻠﺠ مﻮﻠﻋ ﻲﻜﺷﺰﭘ ﻲﻣﻼﺳا دازآ هﺎﮕﺸﻧاد دهرو 21 هرﺎﻤﺷ ، 2 ، نﺎﺘﺴﺑﺎﺗ 90 ، تﺎﺤﻔﺻ 71 ﺎﺗ81 ﺶﻘﻧ هداﻮﻧﺎﺧ يﺎﻫزﺎﻨﻴﻛ ارورآ (Aurora Kinases) رد لﻮﻠﺳ ﻢﻴﺴﻘﺗ و نﺎﻃﺮﺳ نﺎﻣرد ﻲﻳﻮﻟد يرﻮﻧ ﺎﺿر ﺪﻤﺤﻣ 1، يﺮﻛذ ﻲﻠﻋ 2 1 ،ﻲﻜﺷﺰﭘ ﻲﻟﻮﻜﻟﻮﻣ ﻚﻴﺘﻧژ دﺎﺘﺳا ،ﻲﻜﺷﺰﭘ ﻚﻴﺘﻧژ هوﺮﮔ ﻲﻜﺷﺰﭘ هﺪﻜﺸﻧاد ، اد ناﺮﻬﺗ ﻲﻜﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧ ...

Clinical and Experimental Dermatology

PLACK syndrome is a relatively recently defined generalized Peeling Skin Syndrome (PSS) that has ... more PLACK syndrome is a relatively recently defined generalized Peeling Skin Syndrome (PSS) that has been reported with major skin manifestations and sometimes atypical features. Herein, the case of a five-year-old boy with PLACK manifestations is reported. Whole exome sequencing and subsequent Sanger sequencing identified a putative splice variant c.1209 + 2T > G in CAST (NM_001042440.5). Moreover, mRNA sequencing confirmed the abnormal alternative splicing of the CAST gene leading to the addition of one nucleotide to the correct open reading frame at the mRNA level. Segregation and expression analysis revealed that this loss-of-function via mRNA nonsense-mediated decay could be the causative pathogenic mechanism responsible for the patient’s phenotype. This study extends our understanding of the various phenotypic and genotypic features of PLACK disease.

Cancer Microenvironment, 2015

Presence of tumor initiating cells and a proper niche is essential for metastatic colonization. S... more Presence of tumor initiating cells and a proper niche is essential for metastatic colonization. SLUG and SOX9 transcription factors play essential roles in induction and maintenance of tumor initiating capacity in breast cancer cells. On the other hand, Tenascin-C and Periostin are crucial factors in metastatic niche that support tumor initiating capability in breast cancer. In this study, regulatory effect of SLUG and SOX9 transcription factors on the expression of Tenascin-C and Periostin was examined. SLUG and SOX9 were overexpressed and knocked-down in MCF7 and MDA-MB-231 cells, respectively. The cells as little and highly invasive breast cancerderived cells were infected by inducing and shRNA lentivirus constructs. Then, Tenascin-C and Periostin as well as SLUG and SOX9 expression levels were measured in the cells via Real-Time PCR. Simultaneous overexpression of SLUG and SOX9 significantly induced Tenascin-C and Periostin expression. SLUG and SOX9 knock-down also significantly reduced the expression of Tenascin-C and Periostin. In this analysis Periostin showed the most deviation in both up-and downregulation levels. This regulatory effect might shed light to a crosstalk between factors involved in the tumor initiating capacity and metastatic niche of the breast cancer.

Scientific Journal of Iran Blood Transfus Organ, 2013

Background and Objectives Arsenic trioxide (ATO) is an active drug in treatment of acute promyelo... more Background and Objectives Arsenic trioxide (ATO) is an active drug in treatment of acute promyelocytic leukemia (APL), but has adverse effects on patients. In order to enhance antileukemic effectiveness and to reduce dosage of ATO, combinatorial effect of it with Azidothymidine (AZT) in apoptosis induction was evaluated on APL cell line (NB4). Materials and Methods The cells cultured and treated with 50 μM AZT and/or ATO for 48 hrs and then with apoptosis, cell cycle distribution, and P21 mRNA levels in comparison with untreated cells (control) were analyzed by flow cytometry and Real Time PCR, respectively. Results ATO led to induction of apoptosis (50.14% ± 7.12) in comparison with the control (3.9% ± 2.97) through the increment of the cell cycle arrest in G2/M. The apoptotic effect of ATO had been inhibited in cells treated with combination of AZT/ATO (24.35% ± 4.65). This inhibition was associated with the relative reduction of the cells in G2/M and relative increase of the cell...

Archives of Iranian medicine, 2014

Silibinin is a traditionally well-known drug for its hepatoprotective efficacy against various ty... more Silibinin is a traditionally well-known drug for its hepatoprotective efficacy against various types of liver afflictions. In addition, it has recently been considered broadly as a potential chemopreventive agent against many types of cancers. The current study was designed to evaluate the restrictive effects of pharmacological doses of silibinin on SKBR3, an ErbB2-overexpressed and ER-negative human breast carcinoma cell line. Effect of silibinin on metabolic activity and proliferation of human breast carcinoma (SKBR3) cell line were evaluated by MTT and BrdU assays respectively. Furthermore, the proapoptotic effect of silibinin was investigated using flow cytometry. The NF-κB phosphorylation assay was also used to assess the effect of silibinin on NF-κB activation. The alkalizing effect of silibinin on SKBR3 cell line was evaluated by measuring pH of media of the silibinin-treated cells compared to control. Our results indicate that silibinin inhibited metabolic activity and cell ...

Background and Objective: Colorectal cancer (CRC) is the third most prevalent cancer in the world... more Background and Objective: Colorectal cancer (CRC) is the third most prevalent cancer in the world with high rates of mortality, which makes it of great importance to be efficiently cured. Aurora kinase family (including Aurora A, B, and C) regulate several phases of cell cycle in mammalian cells. Aurora-B is overexpressed in various types of solid tumors and leukemia, and in that case, the prognosis is poor. AZD1152 is a selective inhibitor for Aurora kinase B. The purpose of this study is to investigate the effects of AZD1152 and its mechanism of action on two CRC cell lines. Methods: In this experimental study, two cell lines including Caco-2 and HCT-116, were used as models of CRC. Trypsin was utilized for passaging the mentioned cell lines. AZD1152 was provided with primary concentration of 1000 μM and diluted to achieve specific concentrations. Antitumor properties of AZD1152 on cell lines were investigated using MTT (Microculture Tetrazolium Test) and clonogenic assays. Studen...

Reports of biochemistry & molecular biology, 2014

BACKGROUND The study of specific genes expressed in the testis is important to understanding test... more BACKGROUND The study of specific genes expressed in the testis is important to understanding testis development and function. Spermatogenesis is an attractive model for the study of gene expression during germ cell differentiation. Spermatogenesis associated-19 (Spata-19) is a recently-identified important spermatogenesis-related gene specifically expressed in testis. Its protein product is involved in sperm cell development and reproduction. In this report we examined the expression of Spata-19 mRNA in mouse testis, fetus, and cell lines. METHODS Reverse transcription-polymerase chain reaction (RT-PCR), nested PCR, and PCR-restriction fragment length polymorphism (PCR-RFLP) were used to analyze Spata-19 mRNA expression in different stages of mouse testis development, mouse fetus, mouse embryonic fibroblasts (MEF), mouse embryonic stem cells (mESC), Sertoli cells, and NIH/3T3 cells. RESULTS We identified a novel splice variant of Spata-19 in the mouse genome that it is expressed in ...

Frontiers in Anti-Cancer Drug Discovery, 2015

Multidisciplinary Cancer Investigation, Nov 1, 2017

Medical Journal of the Islamic Republic of Iran, 2020

Background: Epidermolysis bullosa simplex is a hereditary skin disorder caused by mutations in se... more Background: Epidermolysis bullosa simplex is a hereditary skin disorder caused by mutations in several genes such as KRT5 and KRT14 . Skin fragility in basal keratinocytes presence regions led to the cytolysis of epidermis and blistering. Aim of this study was to detect the molecular defects in KRT5 and KRT14 genes hot spots in patients with clinical suspicion of EBS and investigation of their probable genotype-phenotype correlations. Methods: Exons 1 and 6-7 of KRT5 and exons 1 and 4-7 of KRT14 amplification and mutation detection were performed by polymerase chain reaction and Sanger sequencing, respectively. Novel variants pathogenicity evaluated by bioinformatics tools. Results: Nine important variants detected in seven different patients within 6 Iranian families affected by Epidermolysis bullosa simplex, of which four variants were novel. Three patients had a mottled pigmentation phenotype [G96D (p.Gly96Asp) and F97I (p.Phe97Ile) in KRT5 ]. One of them showed a Dowling–Meara p...

Background and Objective: Colorectal cancer (CRC) is the third most prevalent cancer in the world... more Background and Objective: Colorectal cancer (CRC) is the third most prevalent cancer in the world with high rates of mortality, which makes it of great importance to be efficiently cured. Aurora kinase family (including Aurora A, B, and C) regulate several phases of cell cycle in mammalian cells. Aurora-B is overexpressed in various types of solid tumors and leukemia, and in that case, the prognosis is poor. AZD1152 is a selective inhibitor for Aurora kinase B. The purpose of this study is to investigate the effects of AZD1152 and its mechanism of action on two CRC cell lines. Methods: In this experimental study, two cell lines including Caco-2 and HCT-116, were used as models of CRC. Trypsin was utilized for passaging the mentioned cell lines. AZD1152 was provided with primary concentration of 1000 μM and diluted to achieve specific concentrations. Antitumor properties of AZD1152 on cell lines were investigated using MTT (Microculture Tetrazolium Test) and clonogenic assays. Studen...

International Journal of Molecular and Cellular Medicine, 2018

Waardenburg syndrome (WS) is a neurocristopathy with an autosomal dominant mode of inheritance, a... more Waardenburg syndrome (WS) is a neurocristopathy with an autosomal dominant mode of inheritance, and considerable clinical and genetic heterogeneity. WS type II is the most common type of WS in many populations presenting with sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eye, and pigmentary abnormalities of the hair and skin. To date, mutations of MITF, SOX10, and SNAI2 have been implicated in the pathogenesis of WS2. Although different pathogenic mutations have been reported in many ethnic groups, the data on Iranian WS2 patients is insufficient. 31 WS2 patients, including 22 men and 9 women from 14 families were included. Waardenburg consortium guidelines were employed for WS2 diagnosis. WS2 patients underwent screening for MITF, SOX10, and SNAI2 mutations using direct sequencing and MLPA analysis. Clinical evaluation revealed prominent phenotypic variability in Iranian WS2 patients. Sensorineural hearing impairment and heterochromia iridis were the most...

Archives of Iranian medicine, 2014

BACKGROUND Silibinin is a traditionally well-known drug for its hepatoprotective efficacy against... more BACKGROUND Silibinin is a traditionally well-known drug for its hepatoprotective efficacy against various types of liver afflictions. In addition, it has recently been considered broadly as a potential chemopreventive agent against many types of cancers. The current study was designed to evaluate the restrictive effects of pharmacological doses of silibinin on SKBR3, an ErbB2-overexpressed and ER-negative human breast carcinoma cell line. METHODS Effect of silibinin on metabolic activity and proliferation of human breast carcinoma (SKBR3) cell line were evaluated by MTT and BrdU assays respectively. Furthermore, the proapoptotic effect of silibinin was investigated using flow cytometry. The NF-κB phosphorylation assay was also used to assess the effect of silibinin on NF-κB activation. The alkalizing effect of silibinin on SKBR3 cell line was evaluated by measuring pH of media of the silibinin-treated cells compared to control. RESULTS Our results indicate that silibinin inhibited m...

Journal of pediatric nephrology, 2020

The novel coronavirus, known as a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), i... more The novel coronavirus, known as a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a single-stranded RNA virus, from which structural and some accessory proteins are encoded. It seems that this newly emerged virus uses the ACE2 receptor to enter the cells in the human body. SARS-CoV-2 undergoes an intense immunological pressure in humans, and this generates mutations to bypass the immune system. Some mutations have been detected in this virus genome, which can induce a change in viral potency. By performing pathway enrichment analysis over those genes and identifying relevant protein-protein interactions (PPIs), we were able to list essential pathways affected in infected cells. In this review, we mainly discuss genetic, intracellular mechanisms, diagnosis and feasible therapeutic targets of this novel coronavirus.

Efforts to discover new anti-cancer drugs are limited by the fact that human and animal models fo... more Efforts to discover new anti-cancer drugs are limited by the fact that human and animal models for testing the effectiveness of drugs are not completely faithful for recapitulation of this complex disease. These models cancer have mainly consisted of cell lines derived from human tumors or Xenografts in mice and more recently, genetically engineered mouse models of human tumor. Cell lines offer an almost infinite supply of similar cells to the genotypes and phenotypes of original tumors. Application of cell lines help scientist to cope with the ethical issues and also resolve the challenge of discrepancy associated with animal studies and human clinical trials.

Frontiers in Oncology

Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a ... more Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a prominent impact in the pathogenesis of breast cancer. Among the transcription factors associated with ESR signaling, FOXM1, GATA3, FOXA1 and ESR1 have been suggested as a candidate in the pathogenesis of this neoplasm. In the current project, we have designed an in silico approach to find long non-coding RNAs (lncRNAs) that regulate these transcription factors. Then, we used clinical samples to carry out validation of our in silico findings. Our systems biology method led to the identification of APTR, AC144450.1, linc00663, ZNF337.AS1, and RAMP2.AS1 lncRNAs. Subsequently, we assessed the expression of these genes in breast cancer tissues compared with the adjacent non-cancerous tissues (ANCTs). Expression of GATA3 was significantly higher in breast cancer tissues compared with ANCTs (Ratio of mean expressions (RME) = 4.99, P value = 3.12E−04). Moreover, expression levels of APTR, AC144...

Acta Physiologica Hungarica, 2014

ABSTRACT Endoplasmic reticulum (ER) stress provides abnormalities in insulin action, inflammatory... more ABSTRACT Endoplasmic reticulum (ER) stress provides abnormalities in insulin action, inflammatory responses, lipoprotein B100 degradation and hepatic lipogenesis. Excess accumulation of triglyceride in hepatocytes may also lead to disorders such as non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Opioid peptides are involved in triglyceride and cholesterol dysregulation, inflammation and cell death. In this study, we evaluated Naltrexone effects on ER stress induced liver injury. To do so, C57/BL6 mice received saline, DMSO and Naltrexone, as control groups. ER stress was induced by tunicamycin (TM) injection. Naltrexone was given before TM administration. Liver blood flow and biochemical serum analysis were measured. Histopathological evaluations, TNF-α measurement and Real-time RT-PCR were also performed. TM challenge provokes steatosis, cellular ballooning and lobular inflammation which significantly reduced in Naltrexone treated animals. ALT, AST and TNF-α increased in the TM group and improved in the Naltrexone plus TM group. Triglyceride and cholesterol levels decreased in TM treated mice with no increase in Naltrexone treated animals. In the Naltrexone plus TM group, gene expression of Bax/Bcl-2 ratio and caspase3 significantly lowered compared with the TM group. In this study, we found that Naltrexone had a notable alleviating role in ER stress induced steatosis and liver injury.