Publications by authors named "Maryam Mahjoubin-Tehran"

26 Publications

  • Page 1 of 1

Streptococcal bacterial components in cancer therapy.

Cancer Gene Ther 2021 Mar 22. Epub 2021 Mar 22.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

The incidence rate of cancer is steadily increasing all around the world, and there is an urgent need to develop novel and more effective treatment strategies. Recently, bacterial therapy has been investigated as a new approach to target cancer, and is becoming a serious option. Streptococcus strains are among the most common and well-studied virulent bacteria that cause a variety of human infections. Everyone has experienced a sore throat during their lifetime, or has been asymptomatically colonized by streptococci. The ability of Streptococcus bacteria to fight cancer was discovered more than 100 years ago, and over the years has undergone clinical trials, but the mechanism is not yet completely understood. Recently, several animal models and human clinical trials have been reported. Streptococcal strains can have an intrinsic anti-tumor activity, or can activate the host immune system to fight the tumor. Bacteria can selectively accumulate and proliferate in the hypoxic regions of solid tumors. Moreover, the bacteria can be genetically engineered to secrete toxins or enzymes that can specifically attack the tumors.
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http://dx.doi.org/10.1038/s41417-021-00308-6DOI Listing
March 2021

Use of  Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches.

Front Oncol 2021 2;11:624759. Epub 2021 Mar 2.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Over the years, conventional cancer treatments, such as chemotherapy with only a limited specificity for tumors, have undergone significant improvement. Moreover, newer therapies such as immunotherapy have undergone a revolution to stimulate the innate as well as adaptive immune responses against the tumor. However, it has been found that tumors can be selectively colonized by certain bacteria, where they can proliferate, and exert direct oncolytic effects as well as stimulating the immune system. Bacterial-mediated cancer therapy (BMCT) is now one example of a hot topic in the antitumor field. is a Gram-negative species that generally causes self-limiting gastroenteritis in humans. This species has been designed and engineered in order to be used in cancer-targeted therapeutics. can be used in combination with other treatments such as chemotherapy or radiotherapy for synergistic modification of the tumor microenvironment. Considerable benefits have been shown by using engineered attenuated strains for the diagnosis and treatment of tumors. Some of these treatment approaches have received FDA approval for early-phase clinical trials. This review summarizes the use of bacteria for cancer therapy, which could pave the way towards routine clinical application. The benefits of this therapy include an automatic self-targeting ability, and the possibility of genetic manipulation to produce newly engineered attenuated strains. Nevertheless, mediated anticancer therapy has not yet been clinically established, and requires more research before its use in cancer treatment.
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http://dx.doi.org/10.3389/fonc.2021.624759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960920PMC
March 2021

Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players.

Front Cardiovasc Med 2020 25;7:588347. Epub 2021 Jan 25.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Unintended cardiac fibroblast proliferation in many pathophysiological heart conditions, known as cardiac fibrosis, results in pooling of extracellular matrix (ECM) proteins in the heart muscle. Transforming growth factor β (TGF-β) as a pivotal cytokine/growth factor stimulates fibroblasts and hastens ECM production in injured tissues. The TGF-β receptor is a heterodimeric receptor complex on the plasma membrane, made up from TGF-β type I, as well as type II receptors, giving rise to Smad2 and Smad3 transcription factors phosphorylation upon canonical signaling. Phosphorylated Smad2, Smad3, and cytoplasmic Smad4 intercommunicate to transfer the signal to the nucleus, culminating in provoked gene transcription. Additionally, TGF-β receptor complex activation starts up non-canonical signaling that lead to the mitogen-stimulated protein kinase cascade activation, inducing p38, JNK1/2 (c-Jun NH2-terminal kinase 1/2), and ERK1/2 (extracellular signal-regulated kinase 1/2) signaling. TGF-β not only activates fibroblasts and stimulates them to differentiate into myofibroblasts, which produce ECM proteins, but also promotes fibroblast proliferation. Non-coding RNAs (ncRNAs) are important regulators of numerous pathways along with cellular procedures. MicroRNAs and circular long ncRNAs, combined with long ncRNAs, are capable of affecting TGF-β/Smad signaling, leading to cardiac fibrosis. More comprehensive knowledge based on these processes may bring about new diagnostic and therapeutic approaches for different cardiac disorders.
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http://dx.doi.org/10.3389/fcvm.2020.588347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868343PMC
January 2021

Autophagy and gastrointestinal cancers: the behind the scenes role of long non-coding RNAs in initiation, progression, and treatment resistance.

Cancer Gene Ther 2021 Jan 11. Epub 2021 Jan 11.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Gastrointestinal (GI) cancers comprise a heterogeneous group of complex disorders that affect different organs, including esophagus, stomach, gallbladder, liver, biliary tract, pancreas, small intestine, colon, rectum, and anus. Recently, an explosion in nucleic acid-based technologies has led to the discovery of long non-coding RNAs (lncRNAs) that have been found to possess unique regulatory functions. This class of RNAs is >200 nucleotides in length, and is characterized by their lack of protein coding. LncRNAs exert regulatory effects in GI cancer development by affecting different functions such as the proliferation and metastasis of cancer cells, apoptosis, glycolysis and angiogenesis. Over the past few decades, considerable evidence has revealed the important role of autophagy in both GI cancer progression and suppression. In addition, recent studies have confirmed a significant correlation between lncRNAs and the regulation of autophagy. In this review, we summarize how lncRNAs play a behind the scenes role in the pathogenesis of GI cancers through regulation of autophagy.
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http://dx.doi.org/10.1038/s41417-020-00272-7DOI Listing
January 2021

Effects of therapeutic probiotics on modulation of microRNAs.

Cell Commun Signal 2021 Jan 11;19(1). Epub 2021 Jan 11.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Probiotics are beneficial bacteria that exist within the human gut, and which are also present in different food products and supplements. They have been investigated for some decades, due to their potential beneficial impact on human health. Probiotics compete with pathogenic microorganisms for adhesion sites within the gut, to antagonize them or to regulate the host immune response resulting in preventive and therapeutic effects. Therefore, dysbiosis, defined as an impairment in the gut microbiota, could play a role in various pathological conditions, such as lactose intolerance, gastrointestinal and urogenital infections, various cancers, cystic fibrosis, allergies, inflammatory bowel disease, and can also be caused by antibiotic side effects. MicroRNAs (miRNAs) are short non-coding RNAs that can regulate gene expression in a post-transcriptional manner. miRNAs are biochemical biomarkers that play an important role in almost all cellular signaling pathways in many healthy and disease states. For the first time, the present review summarizes current evidence suggesting that the beneficial properties of probiotics could be explained based on the pivotal role of miRNAs. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00668-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798223PMC
January 2021

PIWI-interacting RNAs and PIWI proteins in glioma: molecular pathogenesis and role as biomarkers.

Cell Commun Signal 2020 10 27;18(1):168. Epub 2020 Oct 27.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Glioma is the most common primary brain tumor, and is a major health problem throughout the world. Today, researchers have discovered many risk factors that are associated with the initiation and progression of gliomas. Studies have shown that PIWI-interacting RNAs (piRNAs) and PIWI proteins are involved in tumorigenesis by epigenetic mechanisms. Hence, it seems that piRNAs and PIWI proteins may be potential prognostic, diagnostic or therapeutic biomarkers in the treatment of glioma. Previous studies have demonstrated a relationship between piRNAs and PIWI proteins and some of the molecular and cellular pathways in glioma. Here, we summarize recent evidence and evaluate the molecular mechanisms by which piRNAs and PIWI proteins are involved in glioma. Video abstract.
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http://dx.doi.org/10.1186/s12964-020-00657-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590611PMC
October 2020

Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages.

Cell Commun Signal 2020 09 11;18(1):149. Epub 2020 Sep 11.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, IR, Iran.

Exosomes are extracellular vesicles characterized by their size, source, release mechanism and contents. MicroRNAs (miRNAs) are single stranded non-coding RNAs transcribed from DNA. Exosomes and miRNAs are widespread in eukaryotic cells, especially in mesenchymal stem cells (MSCs). MSCs are used for tissue regeneration, and also exert paracrine, anti-inflammatory and immunomodulatory effects. However, the use of MSCs is controversial, especially in the presence or after the remission of a tumor, due to their secretion of growth factors and their migration ability. Instead of intact MSCs, MSC-derived compartments or substances could be used as practical tools for diagnosis, follow up, management and monitoring of diseases. Herein, we discuss some aspects of exosomal miRNAs derived from MSCs in the progression, diagnosis and treatment of various diseases. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00650-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488404PMC
September 2020

Circular RNAs: New Epigenetic Signatures in Viral Infections.

Front Microbiol 2020 31;11:1853. Epub 2020 Jul 31.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.

Covalent closed circular RNAs (circRNAs) can act as a bridge between non-coding RNAs and coding messenger RNAs. CircRNAs are generated by a back-splicing mechanism during post-transcriptional processing and are abundantly expressed in eukaryotic cells. CircRNAs can act via the modulation of RNA transcription and protein production, and by the sponging of microRNAs (miRNAs). CircRNAs are now thought to be involved in many different biological and pathological processes. Some studies have suggested that the expression of host circRNAs is dysregulated in several types of virus-infected cells, compared to control cells. It is highly likely that viruses can use these molecules for their own purposes. In addition, some viral genes are able to produce viral circRNAs (VcircRNA) by a back-splicing mechanism. However, the viral genes that encode VcircRNAs, and their functions, are poorly studied. In this review, we highlight some new findings about the interaction of host circRNAs and viral infection. Moreover, the potential of VcircRNAs derived from the virus itself, to act as biomarkers and therapeutic targets is summarized.
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http://dx.doi.org/10.3389/fmicb.2020.01853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412987PMC
July 2020

Autophagy-related microRNAs: Possible regulatory roles and therapeutic potential in and gastrointestinal cancers.

Pharmacol Res 2020 11 18;161:105133. Epub 2020 Aug 18.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran. Electronic address:

Gastrointestinal (GI) cancers with a high incidence rate and adverse complications are associated with severe morbidity and mortality around the world. It is well recognized that early detection of the disease results in longer survival rate and better quality of life. Autophagy, an intracellular regulatory process, has been shown to play an essential role in the pathogenesis of various malignancies including GI cancers. MicroRNAs (miRNAs) are small non-coding RNAs that have regulatory functions in tumor cells and possess potential diagnostic values in early detection of cancers. It has been recently demonstrated that these molecules have modulatory effects on multiple steps of autophagy process occurring in GI malignancies. In this review, we aimed to highlight the role of autophagy-related microRNAs on GI cancer as potential targets for cancer therapy.
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http://dx.doi.org/10.1016/j.phrs.2020.105133DOI Listing
November 2020

Role of exosomes in malignant glioma: microRNAs and proteins in pathogenesis and diagnosis.

Cell Commun Signal 2020 08 3;18(1):120. Epub 2020 Aug 3.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

Malignant gliomas are the most common and deadly type of central nervous system tumors. Despite some advances in treatment, the mean survival time remains only about 1.25 years. Even after surgery, radiotherapy and chemotherapy, gliomas still have a poor prognosis. Exosomes are the most common type of extracellular vesicles with a size range of 30 to 100 nm, and can act as carriers of proteins, RNAs, and other bioactive molecules. Exosomes play a key role in tumorigenesis and resistance to chemotherapy or radiation. Recent evidence has shown that exosomal microRNAs (miRNAs) can be detected in the extracellular microenvironment, and can also be transferred from cell to cell via exosome secretion and uptake. Therefore, many recent studies have focused on exosomal miRNAs as important cellular regulators in various physiological and pathological conditions. A variety of exosomal miRNAs have been implicated in the initiation and progression of gliomas, by activating and/or inhibiting different signaling pathways. Exosomal miRNAs could be used as therapeutic agents to modulate different biological processes in gliomas. Exosomal miRNAs derived from mesenchymal stem cells could also be used for glioma treatment. The present review summarizes the exosomal miRNAs that have been implicated in the pathogenesis, diagnosis and treatment of gliomas. Moreover, exosomal proteins could also be involved in glioma pathogenesis. Exosomal miRNAs and proteins could also serve as non-invasive biomarkers for prognosis and disease monitoring. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00623-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397575PMC
August 2020

Autophagy-related MicroRNAs in chronic lung diseases and lung cancer.

Crit Rev Oncol Hematol 2020 Sep 18;153:103063. Epub 2020 Jul 18.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran. Electronic address:

Chronic lung disease has become a leading cause of death in recent years. Despite several attempts to discover and develop new therapeutic approaches, patients often suffer a poor quality of life, and are faced with an increased risk of developing lung cancer. Lung cancer often occurs as an end-stage after years of chronic lung disease. An increased understanding of the pathophysiology of chronic lung disease may be obtained from studying the role of autophagy in its initiation and progression. MicroRNAs (miRNAs) play a critical role in the modulation of autophagy, and their deregulation could be associated with the initiation and progression of several chronic lung diseases. Herein, we documented that up/down regulation of miRNAs can activate or inhibit autophagy in chronic lung diseases including lung cancer. Therefore, theses miRNAs could be a promising therapeutic tool for lung cancer specially in drug-resistance lung cancer cells.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103063DOI Listing
September 2020

Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis.

Mol Metab 2020 Jul 13:101049. Epub 2020 Jul 13.

Halal Research Center of IRI, FDA, Tehran, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland. Electronic address:

Objective: The prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NAFLD/NASH) is increasing. NAFLD/NASH may progress to cirrhosis and hepatocellular carcinoma. However, most patients with NAFLD/NASH will die from a vascular cause. There are no approved pharmacological treatments for NASH/NAFLD. Many clinical trials have been, or are being, undertaken; however, the challenge is the assessment of the clinical endpoint. The main objective of this narrative review was to evaluate the efficacy of drugs used in clinical trials for the treatment of NAFLD/NASH that included a liver biopsy as the gold standard.

Methods: A literature search was conducted using 3 databases (PubMed, Scopus, and Google Scholar) to identify the clinical trials that included liver biopsy assessment before and after treatment.

Results: Interventional clinical trials (n = 33) involving 18 different agents, alone and in combination, were identified. Pioglitazone is the only agent that has shown consistent benefit and efficacy in clinical trials. Pentoxifylline, rosiglitazone, and ursodeoxycholic acid had both positive and negative results from clinical trials. There is also evidence for vitamin E and metformin. Other drugs, including bicyclol, cysteamine bitartrate, l-carnitine, liraglutide, obeticholic acid, oligofructose, selonsertib, silymarin, and statins, each had a single clinical study.

Conclusions: In summary, the available molecules demonstrated a significant improvement in NASH and/or liver fibrosis in a minority of patients; thus, other drugs should be identified, possibly those acting on alternative pathophysiological pathways, and tested for their safety and efficacy.
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http://dx.doi.org/10.1016/j.molmet.2020.101049DOI Listing
July 2020

Cyclodextrins: Potential therapeutics against atherosclerosis.

Pharmacol Ther 2020 10 26;214:107620. Epub 2020 Jun 26.

Halal Research Center of IRI, FDA, Tehran, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran. Electronic address:

Atherosclerosis is an inflammatory disease resulting from subendothelial accumulation of lipoprotein-derived cholesterol in susceptible arterial segments, ultimately leading to the formation of clinically significant atherosclerotic plaques. Despite significant advances in the treatment of atherosclerosis, atherosclerotic cardiovascular diseases remain the leading cause of death and disabilities worldwide. Accordingly, there is an urgent need for novel therapies. Cyclodextrins are cyclic oligosaccharides produced from many sources of starch by enzymatic degradation. The frequently used cyclodextrins are α-, β-, and γ-cyclodextrins, which are composed of six, seven, and eight glucose moieties, respectively. Especially β-cyclodextrin can entrap hydrophobic compounds, such as cholesterol, into its hydrophobic cavity and form stable inclusion complexes with cholesterol. This inherent affinity of cyclodextrins has been exploited to extract excess cholesterol from cultured cells, as well as intra- and extracellular cholesterol stores present in atherosclerotic lesions of experimental animals. Accordingly, cyclodextrins could be considered as potentially effective therapeutic agents for the treatment of atherosclerosis. In this review, we address recent advances and the current status of the development of cyclodextrins and provide an update of the latest in vitro and in vivo experiments that pave the way to clinical studies. The emerging therapeutic opportunities by using cyclodextrins could aid us in our efforts to ultimately eradicate the residual risk after other cholesterol-lowering pharmacotherapies, and also reduce the associated burden of premature deaths due to atherosclerotic cardiovascular diseases.
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http://dx.doi.org/10.1016/j.pharmthera.2020.107620DOI Listing
October 2020

TGF-β and WNT signaling pathways in cardiac fibrosis: non-coding RNAs come into focus.

Cell Commun Signal 2020 06 9;18(1):87. Epub 2020 Jun 9.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA, 02114, USA.

Cardiac fibrosis describes the inappropriate proliferation of cardiac fibroblasts (CFs), leading to accumulation of extracellular matrix (ECM) proteins in the cardiac muscle, which is found in many pathophysiological heart conditions. A range of molecular components and cellular pathways, have been implicated in its pathogenesis. In this review, we focus on the TGF-β and WNT signaling pathways, and their mutual interaction, which have emerged as important factors involved in cardiac pathophysiology. The molecular and cellular processes involved in the initiation and progression of cardiac fibrosis are summarized. We focus on TGF-β and WNT signaling in cardiac fibrosis, ECM production, and myofibroblast transformation. Non-coding RNAs (ncRNAs) are one of the main players in the regulation of multiple pathways and cellular processes. MicroRNAs, long non-coding RNAs, and circular long non-coding RNAs can all interact with the TGF-β/WNT signaling axis to affect cardiac fibrosis. A better understanding of these processes may lead to new approaches for diagnosis and treatment of many cardiac conditions. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00555-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281690PMC
June 2020

Autophagy in cancers including brain tumors: role of MicroRNAs.

Cell Commun Signal 2020 06 9;18(1):88. Epub 2020 Jun 9.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA, 02114, USA.

Autophagy has a crucial role in many cancers, including brain tumors. Several types of endogenous molecules (e.g. microRNAs, AKT, PTEN, p53, EGFR, and NF1) can modulate the process of autophagy. Recently miRNAs (small non-coding RNAs) have been found to play a vital role in the regulation of different cellular and molecular processes, such as autophagy. Deregulation of these molecules is associated with the development and progression of different pathological conditions, including brain tumors. It was found that miRNAs are epigenetic regulators, which influence the level of proteins coded by the targeted mRNAs with any modification of the genetic sequences. It has been revealed that various miRNAs (e.g., miR-7-1-3p, miR-340, miR-17, miR-30a, miR-224-3p, and miR-93), as epigenetic regulators, can modulate autophagy pathways within brain tumors. A deeper understanding of the underlying molecular targets of miRNAs, and their function in autophagy pathways could contribute to the development of new treatment methods for patients with brain tumors. In this review, we summarize the various miRNAs, which are involved in regulating autophagy in brain tumors. Moreover, we highlight the role of miRNAs in autophagy-related pathways in different cancers. Video abstract.
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http://dx.doi.org/10.1186/s12964-020-00587-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285723PMC
June 2020

CXCL-10: a new candidate for melanoma therapy?

Cell Oncol (Dordr) 2020 Jun 23;43(3):353-365. Epub 2020 Mar 23.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, I.R., Iran.

Background: Melanoma is a malignancy that stems from melanocytes and is defined as the most dangerous skin malignancy in terms of metastasis and mortality rates. CXC motif chemokine 10 (CXCL10), also known as interferon gamma-induced protein-10 (IP-10), is a small cytokine-like protein secreted by a wide variety of cell types. CXCL10 is a ligand of the CXC chemokine receptor-3 (CXCR3) and is predominantly expressed by T helper cells (Th cells), cytotoxic T lymphocytes (CTLs), dendritic cells, macrophages, natural killer cells (NKs), as well as some epithelial and cancer cells. Similar to other chemokines, CXCL10 plays a role in immunomodulation, inflammation, hematopoiesis, chemotaxis and leukocyte trafficking.

Conclusions: Recent studies indicate that the CXCL10/CXCR3 axis may act as a double-edged sword in terms of pro- and anti-cancer activities in a variety of tissues and cells, especially in melanoma cells and their microenvironments. Most of these activities arise from the CXCR3 splice variants CXCR3-A, CXCR3-B and CXCR3-Alt. In this review, we discuss the pro- and anti-cancer properties of CXCL10 in various types of tissues and cells, particularly melanoma cells, including its potential as a therapeutic target.
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http://dx.doi.org/10.1007/s13402-020-00501-zDOI Listing
June 2020

Exosomal miRNAs: novel players in viral infection.

Epigenomics 2020 02 25;12(4):353-370. Epub 2020 Feb 25.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA 02114, USA.

Exosomes are secreted nanovesicles that are able to transfer their cargo (such as miRNAs) between cells. To determine to what extent exosomes and exosomal miRNAs are involved in the pathogenesis, progression and diagnosis of viral infections. The scientific literature (PubMed and Google Scholar) was searched from 1970 to 2019. The complex biogenesis of exosomes and miRNAs was reviewed. Exosomes contain both viral and host miRNAs that can be used as diagnostic biomarkers for viral diseases. Viral proteins can alter miRNAs, and conversely miRNAs can alter the host response to viral infections in a positive or negative manner. It is expected that exosomal miRNAs will be increasingly used for diagnosis, monitoring and even treatment of viral infections.
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http://dx.doi.org/10.2217/epi-2019-0192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713899PMC
February 2020

Peptide decoys: a new technology offering therapeutic opportunities for breast cancer.

Drug Discov Today 2020 03 21;25(3):593-598. Epub 2020 Jan 21.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Breast cancer is the most common cancer among women. Absence of hormone receptors (estrogen and progesterone) and lack of overexpression of Human Epidermal Growth Factor 2 (HER2) make triple-negative breast cancer (TNBC) an aggressive subtype of breast cancer that is resistant to conventional therapies. Peptide decoys have emerged as a novel therapeutic approach for the treatment of breast cancer. Decoy peptide technology entails the use of soluble proteins or peptides, including binding proteins or inactive cell surface receptors. Peptide decoys bind to certain ligands (e.g., inflammatory cytokines) with high affinity and specificity as receptors but cannot initiate any signaling pathway that is involved in the pathogenesis of breast cancer. In this review, we discuss the use of decoy peptides as a novel therapeutic approach for breast cancer treatment.
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http://dx.doi.org/10.1016/j.drudis.2020.01.010DOI Listing
March 2020

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder.

Curr Med Chem 2021 ;28(2):360-376

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.
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http://dx.doi.org/10.2174/0929867326666191212102407DOI Listing
February 2021

MicroRNAs and exosomes: Small molecules with big actions in multiple myeloma pathogenesis.

IUBMB Life 2020 03 11;72(3):314-333. Epub 2019 Dec 11.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Multiple myeloma (MM), an incurable hematologic malignancy of plasma cells increasing in the bone marrow (BM), has a complex microenvironment made to support proliferation, survival, and drug resistance of tumor cells. MicroRNAs (miRNAs), short non-coding RNAs regulating genes expression at posttranscriptional level, have been indicated to be functionally deregulated or abnormally expressed in MM cells. Moreover, by means of miRNAs, tumor microenvironment also modulates the function of MM cells. Consistently, it has been demonstrated that miRNA levels regulation impairs their interaction with the microenvironment of BM as well as create considerable antitumor feature even capable of overcoming the protective BM milieu. Communication between cancer stromal cells and cancer cells is a key factor in tumor progression. Finding out this interaction is important to develop effective approaches that reverse bone diseases. Exosomes, nano-vehicles having crucial roles in cell-to-cell communication, through targeting their cargos (i.e., miRNAs, mRNAs, DNAs, and proteins), are implicated in MM pathogenesis.
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http://dx.doi.org/10.1002/iub.2211DOI Listing
March 2020

Mesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis?

Stem Cell Res Ther 2019 11 21;10(1):340. Epub 2019 Nov 21.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA, 02114, USA.

Degenerative disorders of joints, especially osteoarthritis (OA), result in persistent pain and disability and high costs to society. Nevertheless, the molecular mechanisms of OA have not yet been fully explained. OA is characterized by destruction of cartilage and loss of extracellular matrix (ECM). It is generally agreed that there is an association between pro-inflammatory cytokines and the development of OA. There is increased expression of matrix metalloproteinase (MMP) and "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS). Mesenchymal stem cells (MSCs) have been explored as a new treatment for OA during the last decade. It has been suggested that paracrine secretion of trophic factors, in which exosomes have a crucial role, contributes to the mechanism of MSC-based treatment of OA. The paracrine secretion of exosomes may play a role in the repair of joint tissue as well as MSC-based treatments for other disorders. Exosomes isolated from various stem cells may contribute to tissue regeneration in the heart, limbs, skin, and other tissues. Recent studies have indicated that exosomes (or similar particles) derived from MSCs may suppress OA development. Herein, for first time, we summarize the recent findings of studies on various exosomes derived from MSCs and their effectiveness in the treatment of OA. Moreover, we highlight the likely mechanisms of actions of exosomes in OA.
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http://dx.doi.org/10.1186/s13287-019-1445-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873475PMC
November 2019

Cancer stem cells as therapeutic targets of pancreatic cancer.

Fundam Clin Pharmacol 2020 Apr 11;34(2):202-212. Epub 2019 Dec 11.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

The discovery of stem cells and their potential abilities in self-renewal and differentiation has opened a new horizon in medicine. Scientists have found a small population of stem cells in some types of cancers with the same functions as normal stem cells. There are two models for tumor progression: clonal (stochastic) and cancer stem cell (CSCs) models. According to the first model, all transformed cells in the tumor have carcinogenic potential and are able to proliferate and produce the same cells. The latter model, which has received more attention recently, considers the role of CSCs in drug resistance and tumor metastasis. Following the model, researchers have found that targeting CSCs may be a promising way in cancer therapy. This review describes CSC characteristics in general, while also focusing on CSC properties in the context of pancreatic cancer.
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http://dx.doi.org/10.1111/fcp.12521DOI Listing
April 2020

Decoy oligodeoxynucleotide technology: an emerging paradigm for breast cancer treatment.

Drug Discov Today 2020 01 25;25(1):195-200. Epub 2019 Oct 25.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, which is resistant to conventional therapies. Therefore, there is an urgent need to identify new therapies for treating incurable breast cancer in patients. Decoy oligodeoxynucleotides (ODNs) are synthetic oligonucleotides that have a high affinity for a specific transcription factor and can be transfected into target cells to bind to their respective target and alter gene transcription. With these powerful tools available, it is highly possible to effectively regulate the expression of genes that are involved in the pathogenesis of breast cancer. Here, we highlight the studies using decoy ODNs for the development of novel therapies against breast cancer.
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http://dx.doi.org/10.1016/j.drudis.2019.10.008DOI Listing
January 2020

Exosomes and cancer: From oncogenic roles to therapeutic applications.

IUBMB Life 2020 04 16;72(4):724-748. Epub 2019 Oct 16.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Exosomes belong to extracellular vehicles that were produced and secreted from most eukaryotic cells and are involved in cell-to-cell communications. They are an effective delivery system for biological compounds such as mRNAs, microRNAs (miRNAs), proteins, lipids, saccharides, and other physiological compounds to target cells. In this way, they could influence on cellular pathways and mediate their physiological behaviors including cell proliferation, tumorigenesis, differentiation, and so on. Many research studies focused on their role in cancers and also on potentially therapeutic and biomarker applications. In the current study, we reviewed the exosomes' effects on cancer progression based on their cargoes including miRNAs, long noncoding RNAs, circular RNAs, DNAs, mRNAs, proteins, and lipids. Moreover, their therapeutic roles in cancer were considered. In this regard, we have given a brief overview of challenges and obstacles in using exosomes as therapeutic agents.
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http://dx.doi.org/10.1002/iub.2182DOI Listing
April 2020

Androgen receptor-related micro RNAs in prostate cancer and their role in antiandrogen drug resistance.

J Cell Physiol 2020 04 10;235(4):3222-3234. Epub 2019 Oct 10.

Bioinformatics Research Group, Mashhad University of Medical Sciences, Mashhad, Iran.

Prostate cancer (PCa) is one of the most common cancers and the fifth most common reason for cancer deaths in the males. Surgical castration combined with androgen deprivation therapy, antiandrogens, and androgen synthesis inhibitors is the current therapeutic modalities for PCa. These strategies inhibit androgen synthesis or reduce its binding to the androgen receptor (AR) but the development of resistance to these therapies and transient responsiveness are challenging issues in the treatment of this cancer. Deregulation of ARs has a vital role in the initiation and progression of PCa. Also, recent findings imply that micro RNAs (miRNAs) are involved in the evolution of PCa and mediate drug resistance in different cancers. Hence, discovering and targeting miRNAs might represent a novel therapeutic approach. This review paid particular attention to the AR pathway and existing information on the possible roles of miRNAs associated with AR pathway and drug resistance to two second-generation antiandrogens, that is, enzalutamide and abiraterone.
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http://dx.doi.org/10.1002/jcp.29275DOI Listing
April 2020

Harnessing nucleic acid-based therapeutics for atherosclerotic cardiovascular disease: state of the art.

Drug Discov Today 2019 05 10;24(5):1116-1131. Epub 2019 Apr 10.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Dyslipidemia is one of the major but modifiable risk factors for atherosclerotic cardiovascular disease (ACVD). Despite the accessibility of statins and other lipid-lowering drugs, the burden of ACVD is still high globally, highlighting the need for new therapeutic approaches. Nucleic acid-based technologies, including antisense oligonucleotides (ASOs), small interfering (si)RNAs, miRNAs, and decoys, are emerging therapeutic modalities for the treatment of ACVD. These technologies aim to degrade gene mRNA transcripts to decrease the levels of atherogenic lipoproteins. Using gene-silencing approaches, the levels of atherogenic lipoproteins can be decreased by targeting proteins that have key roles in lipoprotein metabolism. Here, we highlight preclinical and clinical findings using these approaches for the development of novel therapies against ACVD.
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http://dx.doi.org/10.1016/j.drudis.2019.04.007DOI Listing
May 2019