Publications by authors named "Ali Mohammadi"

332 Publications

The Epidemiology of Chemical Burns Among the Patients Referred to Burn Centers in Shiraz, Southern Iran, 2008-2018.

Bull Emerg Trauma 2021 Oct;9(4):195-200

Department of General Surgery, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Objective: To investigate the prevalence of chemical burns among the patients admitted to Shiraz burn treatment centers.

Methods: It is a descriptive study that was conducted on 62 patients with chemical burns who were admitted between 2008 and 2018. The patients' records were used in the research using the census sampling process. A questionnaire with questions about age, sex, the extent of the burn, the cause of the burn, duration of hospital stay, level of education, incident location, and clinical outcome was used to collect data (survival-death). The data was analyzed by using descriptive statistical methods.

Results: The prevalence of chemical burns was 1% during 2008-2018. Acid and alkali burns were accounted for 93.5% and 6.5% of burns, respectively. 77.4% of patients were male, and 22.6% were female. The mean age of patients was 27 years. The average burn percentage was 16%. 70.6% of patients were illiterate or had primary education. Burns occurred at the workplace and home in 12.9% and 66.1% of cases, respectively. Moreover, Burns occurred due to accident (61%), acid attack (29%), and self-immolation (10%). The average length of hospital stay was 20 days. One patient (1.6%) died from burns.

Conclusion: The study's findings revealed that chemical burns were more common in men than women, and the majority of chemical burns occurred at home. To minimize the occurrence of chemical burns and acid attacks, teaching methods of preventing burns is important at home and work, as well as restricting non-specialists' access to chemicals.
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http://dx.doi.org/10.30476/BEAT.2021.90754.1261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525699PMC
October 2021

HMGA2 Supports Cancer Hallmarks in Triple-Negative Breast Cancer.

Cancers (Basel) 2021 Oct 16;13(20). Epub 2021 Oct 16.

Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, J. B. Winsløws Vej 25, 3, DK-5000 Odense C, Denmark.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that exhibits a high proliferation rate and early metastasis leading to a poor prognosis. HMGA2 is a DNA binding transcriptional regulator implicated in tumorigenesis. Here, we demonstrate that the promoter is demethylated in TNBC tumors, leading to increased expression of HMGA2 at both mRNA and protein levels. Importantly, high HMGA2 levels in TNBC tumors are correlated with poor prognosis. To detail the role of HMGA2 in TNBC development and progression, we studied its effect on core cancer phenotypes. Stable knockdown of HMGA2 in TNBC cells revealed that HMGA2 may support cell proliferation, cell migration and invasion. In addition, HMGA2 knockdown decreased cancer stem cell (CSC) features. Importantly, we found that silencing HMGA2 inhibited NF-kB signaling and lead to decreased expression of the downstream molecules IL-6 and IL-8 and reduced STAT3 pathway activation. Our results demonstrate that HMGA2 supports cancer hallmarks in TNBC and may represent a promising target for TNBC treatment.
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http://dx.doi.org/10.3390/cancers13205197DOI Listing
October 2021

Combination therapy with miR-34a and doxorubicin synergistically induced apoptosis in T-cell acute lymphoblastic leukemia cell line.

Med Oncol 2021 Oct 16;38(12):142. Epub 2021 Oct 16.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

MicroRNAs are identified to take actively part in the development of different cancers. Reduced expression of tumor suppressor miRNAs leads to cancer cell development, so restoring the expression of these miRNAs can be an appropriate treatment option for cancer. Due to the heterogeneity of cancer cells, single-drug therapy often results in drug resistance. Therefore, the combination of chemotherapy with miRNA can be a powerful strategy for cancer treatment. In the current investigation, miR-34a mimic, and negative control were purchased and transfected using jetPEI reagents. Then the synergic effects of miR-34a in combination with doxorubicin were investigated on cell death of acute T-cell lymphoblastic leukemia Jurkat cell line, as well as the expression of some genes including Caspase-3, Bcl-2, and p53 which are involved in apoptosis. Our outcomes showed that this combination remarkably reduced the expression of the Bcl-2 gene, the target gene of miR-34a. According to the results of the MTT assay, the survival rate was significantly decreased compared to the untreated cells. Results of the flow cytometry assay and DAPI staining demonstrated an increased apoptosis rate of Jurkat cells in combination therapy. Moreover, cell cycle arrest was observed at the G2/M phase in cells that were treated with miR-34a/doxorubicin. Most importantly, we showed that the transfection of the Jurkat cells with miR-34a increased the sensitivity of these cells to doxorubicin. Furthermore, the combination of miR-34a and doxorubicin drug effectively increased apoptosis of treated cells. Therefore, this method can be used as an impressive treatment for T-ALL.
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http://dx.doi.org/10.1007/s12032-021-01578-8DOI Listing
October 2021

Non-carcinogenic risk assessment of exposure to heavy metals in underground water resources in Saraven, Iran: Spatial distribution, monte-carlo simulation, sensitive analysis.

Environ Res 2021 Sep 6;204(Pt A):112002. Epub 2021 Sep 6.

Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Italy.

Groundwater aquifers are considered the second most abundant water supply for drinking water all over the world. In Iran, ground waters are commonly employed for drinking water, irrigation, and industrial purposes. Heavy metals (HMs) pose human concerns about the groundwater contamination; these pollutants are recognized to be capable of bio-accumulation, long persistence in the natural environment, and toxic effects. In the present research, the content of HMs: Chromium (Cr), Cadmium (Cd), and Lead (Pb) were detected in 89 water samples collected in 2018 by underground water supplies (active wells) of Saravan city. Hazard Quotient (HQ) and Monte Carlo Simulation approach with 10,000 repetitions were applied to discover the human non-carcinogenic impacts of HMs in four groups of ages (adults, teenagers, children, and infants) of consumers. The concentrations of Cr, Pb, and Cd were in the range of 0.49-20, 0.1 to 58.34, and 0.11-12.8 μg/L, respectively. The mean HQ calculated due to exposure to Pb (0.0018-0.0023), Cr (0.0112-0.0186), and Cd (0.0370-0.0615) were lower than one. The findings of sensitivity analysis revealed that HMs concentration had the most contribution effect on human non-carcinogenic risk analysis in four different exposed populations. This study could assist researchers to perform more comprehensive studies with more samples. Therefore, further research is required for decision-makers to plan proper measurements properly.
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http://dx.doi.org/10.1016/j.envres.2021.112002DOI Listing
September 2021

Glimpse into Cellular Internalization and Intracellular Trafficking of Lipid-Based Nanoparticles in Cancer Cells.

Anticancer Agents Med Chem 2021 Sep 5. Epub 2021 Sep 5.

Departments of Ophthalmology and Visual Sciences, Biomedical Engineering, and Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI . United States.

Lipid-based nanoparticles as drug delivery carriers have been mainly used for delivery of anti-cancer therapeutic agents. Lipid-based nanoparticles, due to their smaller particle size and similarity to cell membranes, are readily internalized into cancer cells. Interestingly, cancer cells also overexpress receptors for specific ligands including folic acid, hyaluronic acid, and transferrin on their surface. This allows the use of these ligands for surface modification of the lipid-based nanoparticle. These modifications then allow the specific recognition of these ligand-coated nanoparticles by their receptors on cancer cells allowing the targeted gradual intracellular accumulation of the functionalized nanoplatforms. These interactions could eventually enhance the internalization of desired drugs via increasing ligand-receptor mediated cellular uptake of the nanoplatforms. The cellular internalization of the nanoplatforms also varies and depends on their physicochemical properties including particle size, zeta potential, and shape. The cellular uptake is also influenced by the types of ligand internalization pathway utilized by cells such as phagocytosis, macropinocytosis, and multiple endocytosis pathways. In this review, we will classify and discuss lipid based nanoparticles engineered to express specific ligands, and are recognized by their receptors on cancer cell, and their cellular internalization pathways. Moreover, the intracellular fate of nanoparticles decorated with specific ligands and the best internalization pathways (caveolae mediated endocytosis) for safe cargo delivery will be discussed.
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http://dx.doi.org/10.2174/1871520621666210906101421DOI Listing
September 2021

Spatial analysis and probabilistic risk assessment of exposure to fluoride in drinking water using GIS and Monte Carlo simulation.

Environ Sci Pollut Res Int 2021 Aug 24. Epub 2021 Aug 24.

Department of Environment and Energy, Sejong University, Seoul, 05006, South Korea.

Prevalence of fluorosis is a worldwide public health problem especially in many states of India. It is necessary to find out the fluoride endemic areas to adopt remedial measures to the people on the risk of fluorosis. The target goals of this research were to assess (a) the exposure of fluoride concentration; (b) probabilistic risk assessment, sensitivity analysis, and uncertainty through intake of groundwater among population of Agra City (infants, children and adults) by Crystal Ball software; and (c) spatial distribution of HQ and fluoride concentration. A total of sixty samples from standing tube wells/hand pumps were gathered from selected and identified fluoride prevalent areas in Agra City. The concentration of fluoride scrutinized was obtained to be ranging from 1.32 to 4.60 mg/L with mean value of 2.36 in Agra City, and more than 91% of samples investigated surpassed the allowable level set for fluoride concentration in potable water 1.5 mg/L, although 9% of the samples were well within the drinking water guidelines (0.5-1.5 mg/L). The hazard quotient (HQ) was obtained to an enormous difference in the exposure dose in infants (1.66-3.91), children (1.87-4.4), and adults (0.92-2.16), correspondingly. The non-carcinogenic HQ values in the group of infants, children, and more than 90% of adults were higher than those of the safety level (i.e., HQ >1). Consequently, the non-carcinogenic risks (HQ level) of fluoride vary from the most to the least: children, infant, and adults, respectively. With 87.41% certainty, the results indicated that the HQ values are between 1 and 3.42. So, infant is the most vulnerable group to fluoride consumption in study area. Uncertainty analysis results indicated that the children group's HQ level was between 1 and 1.90 with 38.48% certainty. To avoid further worsening of the situation as far as health is concerned, remedial actions like alternate sources of water supply and appropriate treatment of water need to be adopted besides required medical attention to affected people.
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http://dx.doi.org/10.1007/s11356-021-16075-8DOI Listing
August 2021

Silencing of HMGA2 by siRNA Loaded Methotrexate Functionalized Polyamidoamine Dendrimer for Human Breast Cancer Cell Therapy.

Genes (Basel) 2021 07 20;12(7). Epub 2021 Jul 20.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 5166-15731, Iran.

The transcription factor high mobility group protein A2 (HMGA2) plays an important role in the pathogenesis of some cancers including breast cancer. Polyamidoamine dendrimer generation 4 is a kind of highly branched polymeric nanoparticle with surface charge and highest density peripheral groups that allow ligands or therapeutic agents to attach it, thereby facilitating target delivery. Here, methotrexate (MTX)- modified polyamidoamine dendrimer generation 4 (G4) (G4/MTX) was generated to deliver specific small interface RNA (siRNA) for suppressing HMGA2 expression and the consequent effects on folate receptor (FR) expressing human breast cancer cell lines (MCF-7, MDA-MB-231). We observed that HMGA2 siRNA was electrostatically adsorbed on the surface of the G4/MTX nanocarrier for constructing a G4/MTX-siRNA nano-complex which was verified by changing the final particle size and zeta potential. The release of MTX and siRNA from synthesized nanocomplexes was found in a time- and pH-dependent manner. We know that MTX targets FR. Interestingly, G4/MTX-siRNA demonstrates significant cellular internalization and gene silencing efficacy when compared to the control. Besides, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay demonstrated selective cell cytotoxicity depending on the folate receptor expressing in a dose-dependent manner. The gene silencing and protein downregulation of HMGA2 by G4/MTX-siRNA was observed and could significantly induce cell apoptosis in MCF-7 and MDA-MB-231 cancer cells compared to the control group. Based on the findings, we suggest that the newly developed G4/MTX-siRNA nano-complex may be a promising strategy to increase apoptosis induction through HMGA2 suppression as a therapeutic target in human breast cancer.
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http://dx.doi.org/10.3390/genes12071102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303903PMC
July 2021

The synergy between miR-486-5p and tamoxifen causes profound cell death of tamoxifen-resistant breast cancer cells.

Biomed Pharmacother 2021 Sep 19;141:111925. Epub 2021 Jul 19.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Breast cancer (BC) is the most common type of malignancy in women. A subset of breast cancers show resistance to endocrine-based therapies. The estrogen receptor (ER) plays a critical role in developing hormone-dependent BC. Loss of ER contributes to resistance to tamoxifen therapy and may contribute to mortality. Thus, it is crucial to overcome this problem. Here, using luciferase reporter assays, qRT-PCR, and Western blot analyses, we demonstrate that the microRNA miR-486-5p targets HMGA1 mRNA, decreasing its mRNA and protein levels in ER-positive (ER+) BC cells. Consistently, miR-486-5p is significantly downregulated, whereas HMGA1 is considerably upregulated in ER+ BC samples. Remarkably, while both miR-486-5p and tamoxifen individually cause G2/M cell cycle arrest, combination treatment synergistically causes profound cell death, specifically in tamoxifen-resistant ER+ cells but not in tamoxifen-sensitive ER+ cells. Combined treatment with miR-486-5p and tamoxifen also additively reduces cell migration, invasion, colony formation, mammary spheroid formation and a CD24CD44 cell population, representing decreased cancer stemness. However, these phenomena are independent of the tamoxifen responsiveness of the ER+ BC cells. Thus, miR-486-5p and tamoxifen exhibit additive and synergistic tumor-suppressive effects, most importantly causing profound cell death specifically in tamoxifen-resistant BC cells. Therefore, our work suggests that combining miR-486-5p replacement therapy with tamoxifen treatment is a promising strategy to treat endocrine therapy-resistant BC.
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http://dx.doi.org/10.1016/j.biopha.2021.111925DOI Listing
September 2021

A novel method for the development of plasmid DNA-loaded nanoliposomes for cancer gene therapy.

Drug Deliv Transl Res 2021 Jul 28. Epub 2021 Jul 28.

Drug Applied Research Center & Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

We aimed to develop a simple yet novel method to prepare plasmid DNA-loaded nanoliposomes for cancer gene therapy. Murine interleukin-12 (mIL-12) pDNA-loaded nanoliposomes were prepared via novel freeze-drying of a monophase solution method. The physicochemical characteristics, cytotoxicity, and transfection efficiency of the prepared nanoliposomes in murine CT-26 colon carcinoma cells were evaluated. Furthermore, tumor progression and survival rate in CT-26 colon carcinoma-bearing BALB/c mice subsequent to direct intratumoral injections were investigated over a period of 40 days. Using this preparation method, nanoliposomes with particle size of around 300 nm and zeta potential of 96.5 mV were obtained. The transmission electron microscope results showed that the liposomes were nano-sized and almost spherical. The agarose gel retardation assay revealed the pDNA encapsulation in the nanoliposomes. The nanoliposomes with 72.4% encapsulation efficiency and low cell toxicity could significantly improve mIL-12 expression by approximately 25-fold relative to the naked mIL-12 pDNA. There was a significant tumor growth inhibition after repeated injections of mIL-12 pDNA-loaded nanoliposomes. This is the first study on the freeze-drying of a monophase solution method as a simple yet novel technique for the preparation of pDNA-loaded nanoliposomes. Given the ease of preparation method and promising in vitro and in vivo characteristics, this investigation demonstrates advances in pDNA lipid formulation for cancer gene therapy.
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http://dx.doi.org/10.1007/s13346-021-01034-0DOI Listing
July 2021

Abundance of antibiotic resistance genes in bacteria and bacteriophages isolated from wastewater in Shiraz.

Mol Biol Res Commun 2021 Jun;10(2):73-83

Department of Water Science and Engineering, School of Agriculture, Shiraz University, Shiraz, Iran.

Generally, the high widespread presence of antimicrobial resistance, and the next freeing into aquatic environments which provide a situation for transmission of these genes in water is because of the abuse of the antimicrobial drugs in both medicine and veterinary medicine. In aquatic environment, bacteriophages could have an important role in sharing antimicrobial resistance genes. The purpose of this study was to assess three important antibiotic resistance genes including two β-lactamases (blaTEM, blaSHV) and sul1 gene, referring to resistance to sulfonamides, in both bacteria and phage DNA fractions of wastewater samples, Shiraz, Iran, using polymerase chain reaction. The prevalence of those genes was extremely high and equal to 100% in bacterial DNA, while these rates were lower in phage DNA fractions as 66.66%, 66.66% and 58.33% for blaTEM, blaSHV and sul1, respectively. In conclusion, detection of mentioned genes in bacterial and phage DNA fractions from ambient water is considerable, so the possibility of harbouring and transferring of antibiotic resistance genes by phages needs to be explored in the future. Also, available data is a reputable endorsement that wastewater is a hotspot for these kinds of genes to spread in the environment. Based on our knowledge, this is the first report of blaTEM and bla SHV and sul1 genes in bacterial and phage DNA fractions insulated from urban wastewater and environment in Iran.
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http://dx.doi.org/10.22099/mbrc.2021.39468.1584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310656PMC
June 2021

Role of Myeloid-derived suppressor cell (MDSC) in autoimmunity and its potential as a therapeutic target.

Inflammopharmacology 2021 Oct 20;29(5):1307-1315. Epub 2021 Jul 20.

Internist, Assistant Professor, Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Myeloid suppressor cells (MDSCs) are an important class of immune-regulating cells that can suppress T cell function. Most of our knowledge about the function of MDSC comes from studies of cancer models. Recent studies, however, have greatly contributed to the description of MDSC involvement in autoimmune diseases. They are known as a cell population that may negatively affect immune responses by regulating the function of CD4 and CD8 cells, which makes them an attractive target for autoimmune diseases therapy. However, many questions about MDSC activation, differentiation, and inhibitory functions remain unanswered. In this study, we have summarized the role of MDSCs in various autoimmune diseases, and the potential of targeting them for therapeutic benefits has been discussed.
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http://dx.doi.org/10.1007/s10787-021-00846-3DOI Listing
October 2021

Effect of Mimic Hypoxia on the Proliferation and Expression of miR-27a, miR-9, miR-370 and their Target Genes in MOLT-4 and KG1a Cell Lines.

Asian Pac J Cancer Prev 2021 Jun 1;22(6):1975-1984. Epub 2021 Jun 1.

Hematology and Blood Banking, Tabriz University of Medical Sciences, Tabriz, Iran.

Objective: The aim of this study was to investigate the effect of mimic hypoxia on proliferation, the expression of significant miRNAs, and genes involved in drug resistance in MOLT-4 and KG1 cell lines.

Materials And Methods: The KG1 and MOLT-4 cell lines were cultured in RPMI 1640 medium supplemented with 20% FBS and 10% FBS respectively. The MTT test was used for determining  the optimum dose of CoCl2 for KG1 and MOLT-4 cell lines. Western blotting was used for the detection of HIF-1a protein and the confirmation of mimic hypoxia induced by CoCl2. For evaluating the effect of mimic hypoxia on proliferation of MOLT-4 and KG1 cell lines, cell counting was done using trypan blue at 24, 48, and 72 hours. Furthermore, the results obtained from cell counting were confirmed with the MTT test. Total RNA was extracted  using the RNX Plus solution kit according to the manufacturer's protocol. The expression of genes and miRNAs was evaluated with real time PCR.

Results: According to this study, mimic hypoxia induced by CoCl2 contributes to the overexpression of drug resistance related genes including MDR1, MRP1, FOXM1, BCL-xl genes, and the suppression of PUMA gene compared to the control group. The results also showed that mimic hypoxia condition leads to the up-regulation of miR-9 and down-regulation of miR-27a and miR-370. Additionally, our outcomes demonstrated that mimic hypoxia has an inhibitory effect on the proliferation of MOLT-4 and KG1 cell lines.

Conclusion: Treatment with CoCl2 has an inhibitory effect on the proliferation of MOLT-4 and KG1 cell lines independent from real hypoxia. Additionally, mimic hypoxia has a substantial effect on the expression of  genes and miRNAs involved in drug resistance. Finally, we are still far away to discover the exact functional mechanisms of hypoxia on drug resistance but these evaluations can provide new perspectives into this field for the upcoming studies.
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http://dx.doi.org/10.31557/APJCP.2021.22.6.1975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418844PMC
June 2021

Therapeutic Aspects of Mesenchymal Stem Cell-Based Cell Therapy with a Focus on Human Amniotic Epithelial Cells in Multiple Sclerosis: A Mechanistic Review.

Int J Stem Cells 2021 Aug;14(3):241-251

Cell Biology and Molecular-Genetics Department, Marand Azad University, Marand, Iran.

Multiple sclerosis (MS) is an inflammatory disease of central nervous system (CNS). The mmune system plays an important role in its pathogenesis. Current treatments are unable to cure patients and prevent the progression of MS lesions. Stem cell-based cell therapy has opened a new window for MS treatment. Stem cells regulate immune responses and improve axonal remyelination. Stem cells can be obtained from different origins such as embryonic, neural, bone marrow, and adipose tissues. But yet there is a challenge for the selection of the best cell source for stem cell therapy. Mesenchymal stem cells (MSCs) are a type of stem cell obtained from different origins and have significant immunomodulatory effects on the immune system. The increasing evidence have suggested that umbilical cord and adipose tissue can be a suitable source for isolation of MSCs. Moreover, human amniotic epithelial cells (hAECs) as novel stem cell origins by having immunoregulatory effects, regenerative effects, and less capacity of antigenicity can be a candidate for MS treatment. This review discussed the mechanistic effects of MSCs with a focus on human amniotic epithelial cells, which can be used to treatment and improvement of outcome in MS disease.
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http://dx.doi.org/10.15283/ijsc21032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429946PMC
August 2021

Molecular characterization of lumpy skin disease virus in Iran (2014-2018).

Arch Virol 2021 Aug 31;166(8):2279-2283. Epub 2021 May 31.

Department of Pathobiology, Faculty of Veterinary Medicine, Shiraz University, Shiraz, Iran.

Lumpy skin disease was first reported in the western provinces of Iran in 2014, and this was followed by several outbreaks throughout the country. In this study, 10 Iranian lumpy skin disease virus (LSDV) samples collected during the period of 2014-2018 were characterized by sequence analysis of the GPCR, LSDV142, and IL10LP genes. Sequence comparison of the respective genes revealed a close relationship between Iranian LSDV isolates and viruses from Asia and Europe. Interestingly, some nucleotide sequence diversity was also observed in the IL10LP genes of the Iranian field isolates.
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http://dx.doi.org/10.1007/s00705-021-05119-6DOI Listing
August 2021

Iron oxide and gold bimetallic radiosensitizers for synchronous tumor chemoradiation therapy in 4T1 breast cancer murine model.

J Mater Chem B 2021 06;9(22):4510-4522

Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran. and Joint Ukraine-Azerbaijan International Research and Education Center of Nanobiotechnology and Functional Nanosystems, Drohobych, Ukraine, Baku, Azerbaijan and Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan 45139-56184, Iran.

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.
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http://dx.doi.org/10.1039/d0tb02561eDOI Listing
June 2021

Effects of Zataria multiflora essential oil on the germinative cells of Echinococcus granulosus.

Parasit Vectors 2021 May 17;14(1):257. Epub 2021 May 17.

Division of Virology, Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.

Background: Novel and more efficient compounds are urgently required for medical treatment of cystic echinococcosis (CE). Germinative cell culture of Echinococcus granulosus could be used for anti-echinococcosis agent tests and other biological studies on CE. This study was performed to establish an in vitro cell culture model for E. granulosus germinative cells and to evaluate the lethal effect of Zataria multiflora essential oil (ZMEO) on the cultured cells.

Methods: The inner surface of germinal layers of CE cysts was scraped, and the obtained materials were trypsinized to obtain a suspension of single germinative cells. Medium 199 was used as the basic culture medium and was supplemented with fetal bovine serum, 2-mercaptoethanol, L-cysteine, L-glutamine, glucose, sodium pyruvate, hydatid fluid, amphotericin B and antibiotics. The cells were cultured at a concentration of 10 cells/ml of culture medium and incubated at 37 °C. The culture medium was replaced every 7 days. Chemical composition of ZMEO was identified by GC-MS analysis. ZMEO was tested at concentrations of 0.5-8 mg/ml. Viability of the cells was assessed by trypan blue exclusion assay.

Results: A significant increase in the cell number was evident at 20, 30 and 45 days after cultivation. At 45 days of cultivation, the number of cells was approximately five-fold higher than on the first day. In GC-MC analysis, carvacrol, p-cymene, g-terpinene and thymol were found to be the main compounds of ZMEO. The lethal effect of ZMEO on the germinative cells at concentrations of 6, 7 and 8 mg/ml was 100% after 60, 25 and 7 min of exposure, respectively.

Conclusions: At 45 days of cultivation, the cell concentration was suitable for the desired in vitro experiments. A high lethal effect of ZMEO on the germinative cells of E. granulosus may be considered an opportunity for the introduction of a novel, more effective and safer therapeutic agent for treatment of CE using an herbal product.
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http://dx.doi.org/10.1186/s13071-021-04765-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127251PMC
May 2021

Effects of self-assembled cell-penetrating peptides and their nano-complexes on ABCB1 expression and activity.

Iran J Basic Med Sci 2021 Mar;24(3):383-390

Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Objectives: Doxorubicin (Dox) is one of the most well-known chemotherapeutics that are commonly applied for a wide range of cancer treatments. However, in most cases, efflux pumps like P-glycoprotein (P-gp), expel the taken drugs out of the cell and decrease the Dox bioavailability. Expression of P-gp is associated with elevated mRNA expression of the ATP-binding cassette B1 (ABCB1) gene.

Materials And Methods: In the current study, different sequences of cell-penetrating peptides (CPPs) containing tryptophan, lysine, and arginine and their nano-complexes were synthesized and their impact on the expression and activity of the ABCB1 gene was evaluated in the A549 lung carcinoma cell line. Furthermore, the cellular uptake of designed CPPs in the A549 cell line was assessed.

Results: The designed peptides, including [W4K4], [WR]3-QGR, R10, and K10 increased Dox cytotoxicity after 48 hr. Furthermore, arginine-rich peptides showed higher cellular uptake. Rhodamin123 accumulation studies illustrated that all the obtained peptides could successfully inhibit the P-gp pump. The designed peptides inhibited the ABCB1 gene expression, of which, [W4K4] resulted in the lowest expression ratio.

Conclusion: [W4K4], [WR]3-QGR, R10, and K10 could successfully increase the Dox cytotoxicity by decreasing the efflux pump gene expression.
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http://dx.doi.org/10.22038/ijbms.2021.51675.11727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087847PMC
March 2021

Construction of a ternary nano-architecture based graphene oxide sheets, toward electrocatalytic determination of tumor-associated anti-p53 autoantibodies in human serum.

Talanta 2021 Aug 19;230:122276. Epub 2021 Mar 19.

Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Almost 13% of all death in the world is related to cancer. One of the major reasons for failing cancer treatment is the late diagnosis of the tumors. Thus, diagnosis at the early stages could be vital for the treatment. Serum autoantibodies, as tumor markers, are becoming interesting targets due to their medical and biological relevance. Among them, anti-p53 autoantibody in human sera is found to be involved in a variety of cancers. Regarding this issue, a novel and sensitive electrochemical biosensor for detection of anti-p53 autoantibody has been developed. For this purpose, a nanocomposite including thionine (as an electron transfer mediator)/chitosan/nickel hydroxide nanoparticles/electrochemically reduced graphene oxide (Th-CS-Ni(OH)NPs-ERGO) as a support platform was fabricated on the surface of glassy carbon electrode via a layer-by-layer manner and characterized through common electrochemical and imaging techniques. Then, p53-antigen was immobilized on the nanocomposite and used in an indirect immunoassay with horseradish peroxidase (HRP)-conjugated secondary antibody and HO as the substrate, following the typical Michaelis-Menten kinetics. Under optimized condition, two techniques, including differential Pulse Voltammetry (DPV) and Electrochemical Impedance Spectroscopy (EIS) as a label free technique, applied for the biomarker detection. The linear ranges and LODs were obtained 0.1-500 pg mL and 0.001 pg mL using DPV and 5-150 pg mL and 0.007 pg mL using EIS, respectively. Furthermore, the proposed biosensor displayed satisfying stability, selectivity, and reproducibility. According to the results, the presented protocol is promising to develop other electrochemical biosensors.
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http://dx.doi.org/10.1016/j.talanta.2021.122276DOI Listing
August 2021

Interplay between MAPK/ERK signaling pathway and MicroRNAs: A crucial mechanism regulating cancer cell metabolism and tumor progression.

Life Sci 2021 Aug 15;278:119499. Epub 2021 Apr 15.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.. Electronic address:

Mitogen-activated protein kinase (MAPK) signal transduction, as a highly conserved signaling pathway, is reported to be involved in various biological events, including metabolic reprogramming, cell proliferation, survival, and differentiation. Mutations in key molecules involved in MAPK/ERK signaling and dysregulation of this pathway are very common events in various human malignancies, which make the MAPK signaling a crucial signaling pathway participating in the regulation of glucose uptake by malignant cells and tumorigenesis. MicroRNAs (miRNAs), as small non-coding RNAs, are critical regulators of gene expression that play key roles in cancer initiation and progression. On the other hand, these small RNAs mutually regulate the MAPK signaling which is often overexpressed in the case of cancer progression; suggesting that crosstalk between miRNAs and this signaling pathway plays a pivotal role in the development of human cancers. Some miRNAs such as miR-20b, miR-34c-3p, miR-152, miR-181a, and miR-302b through inhibiting MAPK signaling, and miR-193a-3p, miR-330-3p, and miR-592 by activating this signaling pathway, play imperative roles in tumorigenesis. Therefore, in this review, we aimed to focus on the interplay between miRNAs and MAPK signaling in the various steps of tumorigenesis, including metabolic regulation, cell proliferation, apoptosis, metastasis, angiogenesis, and drug resistance.
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http://dx.doi.org/10.1016/j.lfs.2021.119499DOI Listing
August 2021

A computational simulation of electromembrane extraction based on Poisson - Nernst - Planck equations.

Anal Chim Acta 2021 May 16;1158:338414. Epub 2021 Mar 16.

School of Mechanical Engineering, College of Engineering, University of Tehran, P.O. Box 11155-4563, Tehran, Iran. Electronic address:

Electromembrane extraction (EME) has attracted a great deal of interest in researchers because of its advantages. For analysis, design and optimization purposes, understanding the ion transport mechanisms in the organic supported liquid membrane (SLM) is of prominent importance, where the interplay between the passive diffusion and electric-driven mass transport across SLM affects the mass transfer. In present work, a 2D numerical simulation is developed to examine the mass transfer behavior and the analyte recovery in EME devices. The presented model is capable of describing the effect of different parameters on the recovery of the EME setup. Initial analyte concentration in the sample solution, SLM thickness, applied potential, permittivity, diffusion coefficient, and the reservoir pH within both the sample and acceptor, can be considered as process variables. Predicted results revealed that the most important factors playing key role in EME, are the analyte diffusivity, distribution coefficient of the analyte as well as the level of protonation in both the donor and acceptor solutions. The proposed model is helpful in predicting the mass transfer behavior of the EME process in practical applications.
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http://dx.doi.org/10.1016/j.aca.2021.338414DOI Listing
May 2021

Association between heavy metals and colon cancer: an ecological study based on geographical information systems in North-Eastern Iran.

BMC Cancer 2021 Apr 15;21(1):414. Epub 2021 Apr 15.

Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Colorectal cancer has increased in Middle Eastern countries and exposure to environmental pollutants such as heavy metals has been implicated. However, data linking them to this disease are generally lacking. This study aimed to explore the spatial pattern of age-standardized incidence rate (ASR) of colon cancer and its potential association with the exposure level of the amount of heavy metals existing in rice produced in north-eastern Iran.

Methods: Cancer data were drawn from the Iranian population-based cancer registry of Golestan Province, north-eastern Iran. Samples of 69 rice milling factories were analysed for the concentration levels of cadmium, nickel, cobalt, copper, selenium, lead and zinc. The inverse distance weighting (IDW) algorithm was used to interpolate the concentration of this kind of heavy metals on the surface of the study area. Exploratory regression analysis was conducted to build ordinary least squares (OLS) models including every possible combination of the candidate explanatory variables and chose the most useful ones to show the association between heavy metals and the ASR of colon cancer.

Results: The highest concentrations of heavy metals were found in the central part of the province and particularly counties with higher amount of cobalt were shown to be associated with higher ASR of men with colon cancer. In contrast, selenium concentrations were higher in areas with lower ASR of colon cancer in men. A significant regression equation for men with colon cancer was found (F(4,137) = 38.304, P < .000) with an adjusted R of 0.77. The predicted ASR of men colon cancer was - 58.36 with the coefficients for cobalt = 120.33; cadmium = 80.60; selenium = - 6.07; nickel = - 3.09; and zinc = - 0.41. The association of copper and lead with colon cancer in men was not significant. We did not find a significant outcome for colon cancer in women.

Conclusion: Increased amounts of heavy metals in consumed rice may impact colon cancer incidence, both positively and negatively. While there were indications of an association between high cobalt concentrations and an increased risk for colon cancer, we found that high selenium concentrations might instead decrease the risk. Further investigations are needed to clarify if there are ecological or other reasons for these discrepancies. Regular monitoring of the amount of heavy metals in consumed rice is recommended.
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http://dx.doi.org/10.1186/s12885-021-08148-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048218PMC
April 2021

The Epidemiology of Burn and Lethal Area of Fifty Percentage (LA50) in Children in Shiraz, Southern Iran.

World J Plast Surg 2021 Jan;10(1):66-70

Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: This study was conducted to assess the epidemiology of burn and lethal area of fifty percentage (LA50) in children in Shiraz, Southern Iran.

Methods: In this case series study, 619 hospitalized burn children from burn centers affiliated to Shiraz University of Medical Sciences, Shiraz, Iran from 2012 to 2016 were enrolled. Demographic characteristics of patients such as age, gender, place and cause of burn, and morality rate were evaluated. LA50 was measured using Probit analysis.

Results: The mean age of patients was 4.4±3.4 years. The mortality rate in burn patients was 8.7% and LA50 of total body surface area (TBSA%) ranged from 40.1% in 2012 to 68.3% in 2016. Although the number of male burn patients (65%) was more than females (35%), the mortality rate in females was more than males (11.4% vs. 7.2%). Scald and flame were the most common causes of burn.

Conclusion: The findings in our burn center comparing burn patients to developed countries showed that LA50 and survival rate were lower denoting to an urgent necessity to promote current policies in burn care and prevention and to decrease the mortality rate too.
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http://dx.doi.org/10.29252/wjps.10.1.66DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016374PMC
January 2021

Evaluation of Vitamin D3 and Calcium Deficiency after Recovery from Extensive Burn.

World J Plast Surg 2021 Jan;10(1):60-65

Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Previous studies in pediatric populations have demonstrated that vitamin D deficiency is common in patients with large burns. The aim of the current comparative study was to investigate the serum level of vitamin D in patients with large burns [>20% total body surface area (TBSA)] after 6 months of therapy.

Methods: This case control study was conducted during 6-month period from 2017 to 2018 in Amiralmomenin Hospital, Shiraz, Iran. Forty two patients with large burns (>20% TBSA) and at least 6 months' post-burn period were enrolled. Also, 42 healthy and age and sex matched controls from those referring for routine check-ups were included for comparison. None of the patients and controls received vitamin D supplements. The serum level of calcium (Ca), parathormone (PTH) and vitamin D were compared between the groups.

Results: There was no significant difference between the two study groups regarding the baseline characteristics including the age (0.085), gender (0.275) and duration of sun exposure (0.894). We found that those with major burns had significantly higher serum levels of PTH (50.48±26.49 33.64±15.80; 0.001). In addition, the serum levels of vitamin D were significantly lower in burn patients compared to healthy controls (18.15±9.18 31.43±16.27; 0.001).

Conclusion: Major burns (≥20% TBSA) are associated with increased serum levels of PTH and decreased serum levels of vitamin D. However, serum levels of calcium are not affected by major burns.
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http://dx.doi.org/10.29252/wjps.10.1.60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016369PMC
January 2021

MiR-142-3p targets HMGA2 and suppresses breast cancer malignancy.

Life Sci 2021 Jul 27;276:119431. Epub 2021 Mar 27.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

MicroRNAs (miRNAs) have the ability to regulate gene expression programs in cells. Hence, altered expression of miRNAs significantly contributes to breast cancer development and progression. Here, we demonstrate that the miRNA miR-142-3p directly targets the 3' untranslated region of HMGA2, which encodes an onco-embryonic protein that is overexpressed in most cancers, including breast cancer. Down regulation of miR-142-3p predicting poor patient survival in grade 3 breast cancer (P-value = 0.045). MiR-142-3p downregulates HMGA2 mRNA and protein levels. Higher miR-142-3p and lower HMGA2 expressed are found in breast cancer versus normal breast tissue (P-value<0.05), and their levels inversely correlate in breast cancers (P-value = 1.46 × 10). We demonstrate that miR-142-3p induces apoptosis and G2/M cell cycle arrest in breast cancer cells. In addition, it inhibits breast cancer stem cell properties and decreases SOX2, NANOG, ALDH and c-Myc expression. MiR-142-3p also decreases cell proliferation through inhibition of the ERK/AKT/STAT3 signaling pathways. Finally, pathway analyses of patient samples suggest that these mechanisms also acting in the tumors of breast cancer patients. Thus, our work identifies HMGA2 as a direct miR-142-3p target and indicates that miR-142-3p is an important suppressor of breast cancer oncogenesis. This identifies miR-142-3p may candidate as a therapeutic molecule for breast cancer treatment.
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http://dx.doi.org/10.1016/j.lfs.2021.119431DOI Listing
July 2021

Nanotechnology against the novel coronavirus (severe acute respiratory syndrome coronavirus 2): diagnosis, treatment, therapy and future perspectives.

Nanomedicine (Lond) 2021 03 8;16(6):497-516. Epub 2021 Mar 8.

Department of Public Health Sciences, University of Miami, Miami, FL 33146, USA.

COVID-19, as an emerging infectious disease, has caused significant mortality and morbidity along with socioeconomic impact. No effective treatment or vaccine has been approved yet for this pandemic disease. Cutting-edge tools, especially nanotechnology, should be strongly considered to tackle this virus. This review aims to propose several strategies to design and fabricate effective diagnostic and therapeutic agents against COVID-19 by the aid of nanotechnology. Polymeric, inorganic self-assembling materials and peptide-based nanoparticles are promising tools for battling COVID-19 as well as its rapid diagnosis. This review summarizes all of the exciting advances nanomaterials are making toward COVID-19 prevention, diagnosis and therapy.
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http://dx.doi.org/10.2217/nnm-2020-0441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938776PMC
March 2021

STAT3 Silencing and TLR7/8 Pathway Activation Repolarize and Suppress Myeloid-Derived Suppressor Cells From Breast Cancer Patients.

Front Immunol 2020 19;11:613215. Epub 2021 Feb 19.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Cancer cells escape immune destruction. From this perspective, myeloid-derived suppressor cells (MDSCs), which are immunosuppressive in various cancers including breast cancer (BC), are significant. However, the precise mechanisms are unknown. We isolated HLA-DRCD33 MDSCs and CD3 T cells from BC patients' peripheral blood and healthy donors through MACS and immunophenotyped by flow cytometry. Transfection of short-interfering RNAs and treatment with a TLR7/8 agonist altered pathway activities . Gene expression was analyzed using qRT-PCR, western blotting, and immunohistochemistry. Our findings showed an association between the progression of BC and increased levels of circulating HLA-DRCD33 MDSCs. These cells strongly suppress both autologous and analogous CD3 T cell proliferation and enter the tumor microenvironment. We also identified increased STAT3 signaling and increased IDO and IL-10 expression in BC-derived MDSCs as immunosuppression mechanisms. Further, STAT3 inhibition and TLR7/8 pathway stimulation reduce the immunosuppressive activity of patient-derived MDSCs on T cells by inducing MDSC repolarization and differentiation into mature myeloid cells. This also alters the expression of critical cytokines and transcription factors in CD3 T cells and, importantly, reduces breast cancer cells' proliferation. Finally, while chemotherapy is able to significantly reduce circulating MDSCs' level in patients with breast cancer, these MDSCs remained highly T cell-suppressive. We identified a novel molecular mechanism of MDSC-mediated immunosuppression. STAT3 inhibition and TLR7/8 pathway stimulation in MDSCs repolarize and suppress MDSCs from breast cancer patients. This offers new opportunities for BC immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2020.613215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933669PMC
June 2021

miR-34a and miR-200c Have an Additive Tumor-Suppressive Effect on Breast Cancer Cells and Patient Prognosis.

Genes (Basel) 2021 02 12;12(2). Epub 2021 Feb 12.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran.

Breast cancer is the most common women's malignancy in the world and, for subgroups of patients, treatment outcomes remain poor. Thus, more effective therapeutic strategies are urgently needed. MicroRNAs (miRNAs) have emerged as promising therapeutic tools and targets, as they play significant roles in regulating key cellular processes by suppressing gene expression. However, additive opportunities involving miRNAs have been underexplored. For example, both miR-34a and miR-200c individually suppress the development of different types of cancer, but the cellular effects of their combined actions remain unknown. Here, we show that miR-34a and miR-200c levels are reduced in breast tumors compared to adjacent normal tissues and that this additively predicts poor patient survival. In addition, in cell lines, miR-34a and miR-200c additively induce apoptosis and cell cycle arrest, while also inhibiting proliferation, invasion, migration, stemness and epithelial-to-mesenchymal transition (EMT). Mechanistically, both miRNA-34a and miR-200c directly target HIF1-α and subsequently downregulate VEGFR, MMP9 and CXCR4, although combined miRNA-34a and miR-200c delivery suppresses mouse xenograft tumor development as effectively as individual delivery. We establish a model, supported by in vitro and clinical data, which collectively suggest that the co-delivery of miR-34a and miR-200c represents a promising novel therapeutic strategy for breast cancer patients.
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http://dx.doi.org/10.3390/genes12020267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918749PMC
February 2021

HMGA2 as a Critical Regulator in Cancer Development.

Genes (Basel) 2021 02 13;12(2). Epub 2021 Feb 13.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran.

The high mobility group protein 2 (HMGA2) regulates gene expression by binding to AT-rich regions of DNA. Akin to other DNA architectural proteins, HMGA2 is highly expressed in embryonic stem cells during embryogenesis, while its expression is more limited at later stages of development and in adulthood. Importantly, HMGA2 is re-expressed in nearly all human malignancies, where it promotes tumorigenesis by multiple mechanisms. HMGA2 increases cancer cell proliferation by promoting cell cycle entry and inhibition of apoptosis. In addition, HMGA2 influences different DNA repair mechanisms and promotes epithelial-to-mesenchymal transition by activating signaling via the MAPK/ERK, TGFβ/Smad, PI3K/AKT/mTOR, NFkB, and STAT3 pathways. Moreover, HMGA2 supports a cancer stem cell phenotype and renders cancer cells resistant to chemotherapeutic agents. In this review, we discuss these oncogenic roles of HMGA2 in different types of cancers and propose that HMGA2 may be used for cancer diagnostic, prognostic, and therapeutic purposes.
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http://dx.doi.org/10.3390/genes12020269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917704PMC
February 2021
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