Publications by authors named "Reza Jafari"

68 Publications

Evaluation of Toll-like receptor 3 (TLR3) signaling pathway genes and its genetic polymorphisms in ectopic and eutopic endometrium of women with endometriosis.

J Gynecol Obstet Hum Reprod 2021 Apr 20:102153. Epub 2021 Apr 20.

Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Electronic address:

Objective: Toll-like receptors (TLRs, as members of the innate immune system) are expressed in the human endometrium and their aberrant regulation and expression are involved in the pathogenesis of endometrial diseases. This study is aimed at evaluation of TLR3 signaling pathway genes and its genetic changes in endometriosis patients.

Materials And Methods: Blood samples were collected from 83 endometriosis patients and 93 healthy fertile women and PCR was performed in blood-derived DNA for detection of SNP of TLR3. Also, ectopic (EC) and eutopic (EU) endometrial biopsies were obtained from endometriosis patients (n=20), as well as endometrium from healthy women (n=16, CE). Q-PCR was performed for determination of mRNA expression level of TLR3 signaling pathway genes (TLR3, TICAM, NF-kB1A, CXCL10, IRF3, IFN-B1, IL-6 and IL-8). Also, serum protein levels of TLR3, IFN-β, IL-6 and IL-8 were determined using ELISA.

Results: The mRNA expression levels of TLR3, NF-kB1A, IFN-B1, IRF3, TICAM1, IL-6 and IL-8 were significantly higher in EU compared to ectopic ones and also compared to CE. SNPs frequency (rs3775291 and rs3775290) was not significantly different between patients and controls. Serum protein levels of TLR3, IFN-β, IL-6 and IL-8 were significantly increased in endometriosis patients.

Conclusion: Significant changes were observed in the expression of IL-6 and IL-8 cytokines and other genes in TLR3 cascade in diseased EU, demonstrating that EU similarly to EC is in an intensive inflammatory state. These fundamental alterations in the concept of immune response in EU may lead to its activation, escapes from apoptosis, and displaced implantation of the endometrium.
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http://dx.doi.org/10.1016/j.jogoh.2021.102153DOI Listing
April 2021

Immunopharmacological perspective on zinc in SARS-CoV-2 infection.

Int Immunopharmacol 2021 Apr 1;96:107630. Epub 2021 Apr 1.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

The novel SARS-CoV-2 which was first reported in China is the cause of infection known as COVID-19. In comparison with other coronaviruses such as SARS-CoV and MERS, the mortality rate of SARS-CoV-2 is lower but the transmissibility is higher. Immune dysregulation is the most common feature of the immunopathogenesis of COVID-19 that leads to hyperinflammation. Micronutrients such as zinc are essential for normal immune function. According to the assessment of WHO, approximately one-third of the world's society suffer from zinc deficiency. Low plasma levels of zinc are associated with abnormal immune system functions such as impaired chemotaxis of polymorphonuclear cells (PMNs) and phagocytosis, dysregulated intracellular killing, overexpression of the inflammatory cytokines, lymphopenia, decreased antibody production, and sensitivity to microbes especially viral respiratory infections. Zinc exerts numerous direct and indirect effects against a wide variety of viral species particularly RNA viruses. The use of zinc and a combination of zinc-pyrithione at low concentrations impede SARS-CoV replication in vitro. Accordingly, zinc can inhibit the elongation step of RNA transcription. Furthermore, zinc might improve antiviral immunity by up-regulation of IFNα through JAK/STAT1 signaling pathway in leukocytes. On the other hand, zinc supplementation might ameliorate tissue damage caused by mechanical ventilation in critical COVID-19 patients. Finally, zinc might be used in combination with antiviral medications for the management of COVID-19 patients. In the current review article, we review and discuss the immunobiological roles and antiviral properties as well as the therapeutic application of zinc in SARS-CoV-2 and related coronaviruses infections.
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http://dx.doi.org/10.1016/j.intimp.2021.107630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015651PMC
April 2021

Nanoparticle-mediated synergistic chemoimmunotherapy for tailoring cancer therapy: recent advances and perspectives.

J Nanobiotechnology 2021 Apr 17;19(1):110. Epub 2021 Apr 17.

Biotechnology Research Center, and Faculty of Pharmacy, Tabriz University of Medical Science, 5166-15731, Tabriz, Iran.

Nowadays, a potent challenge in cancer treatment is considered the lack of efficacious strategy, which has not been able to significantly reduce mortality. Chemoimmunotherapy (CIT) as a promising approach in both for the first-line and relapsed therapy demonstrated particular benefit from two key gating strategies, including chemotherapy and immunotherapy to cancer therapy; therefore, the discernment of their participation and role of potential synergies in CIT approach is determinant. In this study, in addition to balancing the pros and cons of CIT with the challenges of each of two main strategies, the recent advances in the cancer CIT have been discussed. Additionally, immunotherapeutic strategies and the immunomodulation effect induced by chemotherapy, which boosts CIT have been brought up. Finally, harnessing and development of the nanoparticles, which mediated CIT have expatiated in detail.
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http://dx.doi.org/10.1186/s12951-021-00861-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052859PMC
April 2021

Simultaneous inhibition of CD73 and IL-6 molecules by siRNA-loaded nanoparticles prevents the growth and spread of cancer.

Nanomedicine 2021 Mar 24;34:102384. Epub 2021 Mar 24.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

High concentrations of adenosine and interleukin (IL)-6 in the tumor microenvironment have been identified as one of the leading causes of cancer growth. Thus, we decided to inhibit the growth of cancer cells by inhibiting the production of adenosine and IL-6 in the tumor environment at the same time. For this purpose, we used chitosan-lactate-PEG-TAT (CLP-TAT) nanoparticles (NPs) loaded with siRNA molecules against CD73, an adenosine-producing enzyme, and IL-6. Proper physicochemical properties of the produced NPs led to high cell uptake and suppression of target molecules. Administration of these NPs to tumor-bearing mice (4T1 and CT26 models) greatly reduced the size of the tumor and increased the survival of the mice, which was accompanied by an increase in anti-tumor T lymphocyte responses. These findings suggest that combination therapy using siRNA-loaded CLP-TAT NPs against CD73 and IL-6 molecules could be an effective treatment strategy against cancer that needs further study.
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http://dx.doi.org/10.1016/j.nano.2021.102384DOI Listing
March 2021

An Eco-Epidemiological Study on Zoonotic Cutaneous Leishmaniasis in Central Iran.

Iran J Public Health 2021 Feb;50(2):350-359

Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Leishmaniasis is an expanding neglected tropical disease in the world reporting from 98 countries including Iran. This study focused on eco-epidemiological determinants of the disease following a rapid and unexpected increase of leishmaniasis incidence in a strategic residential district in North-East of Isfahan County, Iran.

Methods: This study was accomplished from Apr 2012 to Jan 2014 in a strategic residential zone in North-East of Isfahan County, Esfahan, Iran. Monthly activity, parity, infection and susceptibility tests, were determined on sand flies. Some portion of inhabitants and school children were surveyed to find active or passive cases of leishmaniasis and also wild rodents were collected to determine reservoir host.

Results: Totally 5223 sand flies belonging to and genus were collected and identified; was the dominant species and started to appear in May and disappeared in Oct. The majority of living dissected sand flies were unfed and parous. showed 4.6% infection through direct examination and 39.54% by nested-PCR respectively. was susceptible against deltametrin 0.05%. Totally 2149 people were surveyed and incidence and prevalence of zoonotic cutaneous leishmaniasis estimated as 45.39 and 314.40 per 1000 population. Rodents showed 73.91% and 80% infection by direct examination and nested-PCR respectively.

Conclusion: Cutaneous leishmaniasis due to has been established in this area. Rodent control operation and personal protection are highly recommended to control the disease in this focus.
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http://dx.doi.org/10.18502/ijph.v50i2.5350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956076PMC
February 2021

Neurological manifestations of COVID-19: with emphasis on Iranian patients.

J Neurovirol 2021 Mar 12. Epub 2021 Mar 12.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has instigated a global pandemic as a formidable and highly contagious infectious disease. Although the respiratory system remains the most frequently affected organ, several case reports have revealed that the complications are not merely limited to the respiratory system, and neurotropic and neuroinvasive properties have also been observed, leading to neurological diseases. In the present paper, it was intended to review the possible neuroinvasive routes of SARS-CoV-2 and its mechanisms that may cause neurological damage. Additionally, the neurological manifestations of COVID-19 across the globe were discussed with emphasis on Iran, while highlighting the impact of SARS-CoV-2 on the central and peripheral nervous systems.
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http://dx.doi.org/10.1007/s13365-021-00964-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953513PMC
March 2021

Exosomes for mRNA delivery: a novel biotherapeutic strategy with hurdles and hope.

BMC Biotechnol 2021 Mar 10;21(1):20. Epub 2021 Mar 10.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Shafa St, Ershad Blvd, P.O. BoX: 1138, Urmia, 57147, Iran.

Over the past decade, therapeutic messenger RNAs (mRNAs) have emerged as a highly promising new class of drugs for protein replacement therapies. Due to the recent developments, the incorporation of modified nucleotides in synthetic mRNAs can lead to maximizing protein expression and reducing adverse immunogenicity. Despite these stunning improvements, mRNA therapy is limited by the need for the development of safe and efficient carriers to protect the mRNA integrity for in vivo applications. Recently, leading candidates for in vivo drug delivery vehicles are cell-derived exosomes, which have fewer immunogenic responses. In the current study, the key hurdles facing mRNA-based therapeutics, with an emphasis on recent strategies to overcoming its immunogenicity and instability, were highlighted. Then the immunogenicity and toxicity of exosomes derived from various cell sources were mentioned in detail. Finally, an overview of the recent strategies in using exosomes for mRNA delivery in the treatment of multiple diseases was stated.
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http://dx.doi.org/10.1186/s12896-021-00683-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945253PMC
March 2021

Adverse effects of brimonidine eye drop in children: A case series.

J Clin Pharm Ther 2021 Feb 24. Epub 2021 Feb 24.

Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

What Is Known And Objective: Brimonidine is increasingly used in the treatment of intraocular hypertension.

Case Summary: We report on five paediatric patients suffering from brimonidine eye drop intoxication. The most frequent signs of the intoxication were a lowered level of consciousness and hypotonia. Other complications were apnea, bradycardia, hypotension and seizure. One of the patients needed cardiopulmonary resuscitation. Apnea in one of the cases was resistant to naloxone. Pupils were unremarkable in two cases.

What Is New And Conclusion: Brimonidine is potentially lethal for young infants. The absence of miosis and absence of response to naloxone is not a reason to rule out brimonidine poisoning.
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http://dx.doi.org/10.1111/jcpt.13401DOI Listing
February 2021

Advances in immunotherapy for COVID-19: A comprehensive review.

Int Immunopharmacol 2021 Apr 22;93:107409. Epub 2021 Jan 22.

School of Medicine, Shahroud University of Medical Sciences. Shahroud, Iran. Electronic address:

COVID-19 is an acute respiratory syndrome caused by SARS-COV-2 which has now become a huge pandemic worldwide. The immunopathogenesis of COVID-19 has been established that increased serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and reduction of the CD4+ and the CD8+ T lymphocyte populations, are the most reported immunological findings in these patients. High levels of other inflammatory cytokines and chemokines such as IL-2 and IL-8 with an increased number of neutrophils and eosinophils may induce immune abnormalities in patients with COVID-19. There is growing evidence to obtain a deeper understanding of the immunopathogenesis of COVID-19 which will lay the foundation for the development of new potential therapies. However, specific and non-specific immunotherapies such as convalescent plasma (CP) are widely performed to treat patients with severe COVID-19, there is no definitive evidence to suggest the effectiveness of these treatments. Hence, this review aimed to highlight the current and most recent studies to identify the new immunotherapeutics for COVID-19 disease.
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http://dx.doi.org/10.1016/j.intimp.2021.107409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826020PMC
April 2021

Stability of Imbalanced Triangles in Gene Regulatory Networks of Cancerous and Normal Cells.

Front Physiol 2020 20;11:573732. Epub 2021 Jan 20.

Physics Department, Shahid Beheshti University, Tehran, Iran.

Genes communicate with each other through different regulatory effects, which lead to the emergence of complex network structures in cells, and such structures are expected to be different for normal and cancerous cells. To study these differences, we have investigated the Gene Regulatory Network (GRN) of cells as inferred from RNA-sequencing data. The GRN is a signed weighted network corresponding to the inductive or inhibitory interactions. Here we focus on a particular of motifs in the GRN, the triangles, which are imbalanced if the number of negative interactions is odd. By studying the stability of imbalanced triangles in the GRN, we show that the network of cancerous cells has fewer imbalanced triangles compared to normal cells. Moreover, in the normal cells, imbalanced triangles are isolated from the main part of the network, while such motifs are part of the network's giant component in cancerous cells. Our result demonstrates that due to genes' collective behavior the structure of the complex networks is different in cancerous cells from those in normal ones.
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http://dx.doi.org/10.3389/fphys.2020.573732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854919PMC
January 2021

The role of regulatory T cells in the pathogenesis and treatment of prostate cancer.

Life Sci 2021 Jan 26:119132. Epub 2021 Jan 26.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Despite developments in the treatment of various cancers, prostate cancer is one of the deadliest diseases known to men. Systemic therapies such as androgen deprivation, chemotherapy, and radiation therapy have not been very successful in treating this disease. Numerous studies have shown that there is a direct relationship between cancer progression and inhibition of anti-tumor immune responses that can lead to progression of various malignancies, including prostate cancer. Interestingly, CD4CD25FoxP3 regulatory T cells significantly accumulate and increase in draining lymph nodes and PBMCs of patients with prostate cancer and other solid tumors. In vivo and in vitro studies have shown that Tregs can suppress anti-tumor responses, which is directly related to the increased risk of cancer recurrence. Tregs are essential for preserving self-tolerance and inhibiting extra immune responses harmful to the host. Since the tumor-related antigens are mainly self-antigens, Tregs could play a major role in tumor progression. Accordingly, it has discovered that prostate cancer patients with higher Tregs have poor prognosis and low survival rates. However, anti-tumor responses can be reinforced by suppression of Tregs with using monoclonal antibodies against CD25 and CTLA-4. Therefore, depleting Tregs or suppressing their functions could be one of the effective ways for prostate cancer immunotherapy. The purpose of this review is to investigate the role of Treg cells in the progression of prostate cancer and to evaluate effective strategies for the treatment of prostate cancer by regulating Treg cells.
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http://dx.doi.org/10.1016/j.lfs.2021.119132DOI Listing
January 2021

The tumorigenic and therapeutic functions of exosomes in colorectal cancer: Opportunity and challenges.

Cell Biochem Funct 2021 Jan 24. Epub 2021 Jan 24.

Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.

Most cells release extracellular vesicles (EVs) mediating intercellular communication via transferring various biomolecules including proteins, nucleic acids, and lipids. A subset of EVs is exosomes that promote tumorigenesis. Different tumour cells such as colorectal cancer (CRC) cells produce exosomes that participate in the progression of CRC. Exosomes cargo including proteins and miRNAs not only support proliferation and metastasis of tumour cells but also mediate chemoresistance, immunomodulation and angiogenesis. In addition, as exosomes are present in most body fluids, they can hold the great capacity for clinical usage in early diagnosis and prognosis of CRC. Exosomes from CRC (CRC-Exo) differentially contain proteins and miRNAs that make them a promising candidate for CRC diagnosis by a simple liquid-biopsy. Despite hopeful results, some challanges about exosomes terminology and definition remains to be clarified in further experiments. In addition, there are little clinical trials regarding the application of exosomes in CRC treatment, therefore additional studies are essential focusing on exosome biology and translation of preclinical findings into the clinic. The present study discusses the key role of exosomes in CRC progression and diagnosis. Furthermore, it describes the opportunity and challenges associated with using exosomes as tumour markers.
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http://dx.doi.org/10.1002/cbf.3622DOI Listing
January 2021

Monocytes and macrophages in COVID-19: Friends and foes.

Life Sci 2021 Mar 14;269:119010. Epub 2021 Jan 14.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

The COVID-19 is a novel infectious disease caused by SARS-CoV-2 and is known as a pandemic emergency that has led to a high rate of mortality throughout the world. Evidence has indicated that hyperinflammatory responses triggered by SARS-CoV-2 are the main cause of pathogenicity in the severe cases of patients who have died during the current viral disease. Monocytes and macrophages as the most important cells of the innate arm of the immune system play a substantial part in the body's defense against viral infections. They mainly respond to the microbial antigens by producing inflammatory mediators to remove pathogens and repair tissue injury. Nevertheless, aberrant alterations in their function such as cytokine storm can be so harmful to the host in the acute respiratory distress syndrome cases caused by SARS-CoV-2. Moreover, inflammatory responses stimulated by SARS-CoV-2 have affected the other vital organs of the body including the heart. As cardiovascular complications in COVID-19 patients have been reported in several studies. During the infection, monocytes and macrophages may be involved in the hypersensitive and exacerbated reactions that contribute to the tissue damage, especially lung injury resulted in its dysfunction and respiratory disorder. In this review, we discuss both advantageous and disadvantageous about the pathological potential of monocytes and macrophages during the infection of SARS-CoV-2 to clarify their mutual effects on immune processing as a fist line defender in the current disease.
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http://dx.doi.org/10.1016/j.lfs.2020.119010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834345PMC
March 2021

The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application.

Cell Biosci 2021 Jan 15;11(1):19. Epub 2021 Jan 15.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Shafa St, Ershad Blvd., P.O. Box: 1138, 57147, Urmia, Iran.

Eukaryotic cells produce extracellular vesicles (EVs) mediating intercellular communication. These vesicles encompass many bio-molecules such as proteins, nucleic acids, and lipids that are transported between cells and regulate pathophysiological actions in the recipient cell. Exosomes originate from multivesicular bodies inside cells and microvesicles shed from the plasma membrane and participate in various pathological conditions. Retroviruses such as Human Immunodeficiency Virus -type 1 (HIV-1) and Human T-cell leukemia virus (HTLV)-1 engage exosomes for spreading and infection. Exosomes from virus-infected cells transfer viral components such as miRNAs and proteins that promote infection and inflammation. Additionally, these exosomes deliver virus receptors to target cells that make them susceptible to virus entry. HIV-1 infected cells release exosomes that contribute to the pathogenesis including neurological disorders and malignancy. Exosomes can also potentially carry out as a modern approach for the development of HIV-1 and HTLV-1 vaccines. Furthermore, as exosomes are present in most biological fluids, they hold the supreme capacity for clinical usage in the early diagnosis and prognosis of viral infection and associated diseases. Our current knowledge of exosomes' role from virus-infected cells may provide an avenue for efficient retroviruses associated with disease prevention. However, the exact mechanism involved in retroviruses infection/ inflammation remains elusive and related exosomes research will shed light on the mechanisms of pathogenesis.
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http://dx.doi.org/10.1186/s13578-021-00537-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810184PMC
January 2021

Emerging of Cutaneous Leishmaniais Due to in a New Focus in Esfahan Province, Central Iran.

J Arthropod Borne Dis 2020 Jun 30;14(2):134-143. Epub 2020 Jun 30.

Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Esfahan Province is considered as one of the main focus of zoonotic cutaneous leishmaniasis (ZCL) in Iran. Recently, ZCL distribution is expanding through this province leading to report of new cases in non-endemic areas. In the current study epidemiological aspects of ZCL has been investigated in Naein County in Esfahan Province.

Methods: Adult sand flies were collected from beginning to the end of their seasonal activity. Rodents were caught by Sherman live traps once a month for one year. To active case detection, a hundred households in each selected village were visited in November and December 2016. Nested-PCR was employed to detect parasite in the vector, reservoir and human.

Results: Totally 1562 sand flies including , , and were collected and identified. No infection was detected in the collected sand flies. All of the 30 collected rodents were identified as , and of these 3.3% and 26.7% were infected by using microscopic and molecular technique respectively. Totally, 914 individuals were investigated and the ulcer and scar rates of ZCL calculated to be at 1.1 and 15.3 per 1000 population, respectively. Molecular results confirmed infection in human and reservoir samples.

Conclusion: It is concluded that ZCL is established in the area in low endemicity, and it is extrapolated the disease will not be a serious increasing health problem in the near future in this region.
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http://dx.doi.org/10.18502/jad.v14i2.3731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738932PMC
June 2020

Hypoxic exosomes orchestrate tumorigenesis: molecular mechanisms and therapeutic implications.

J Transl Med 2020 12 10;18(1):474. Epub 2020 Dec 10.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Shafa St, Ershad Blvd, P.O. BoX: 1138, 57147, Urmia, Iran.

The solid tumor microenvironment possesses a hypoxic condition, which promotes aggressiveness and resistance to therapies. Hypoxic tumor cells undergo broadly metabolic and molecular adaptations and communicate with surrounding cells to provide conditions promising for their homeostasis and metastasis. Extracellular vesicles such as exosomes originating from the endosomal pathway carry different types of biomolecules such as nucleic acids, proteins, and lipids; participate in cell-to-cell communication. The exposure of cancer cells to hypoxic conditions, not only, increases exosomes biogenesis and secretion but also alters exosomes cargo. Under the hypoxic condition, different signaling pathways such as HIFs, Rab-GTPases, NF-κB, and tetraspanin are involved in the exosomes biogenesis. Hypoxic tumor cells release exosomes that induce tumorigenesis through promoting metastasis, angiogenesis, and modulating immune responses. Exosomes from hypoxic tumor cells hold great potential for clinical application and cancer diagnosis. Besides, targeting the biogenesis of these exosomes may be a therapeutic opportunity for reducing tumorigenesis. Exosomes can serve as a drug delivery system transferring therapeutic compounds to cancer cells. Understanding the detailed mechanisms involved in biogenesis and functions of exosomes under hypoxic conditions may help to develop effective therapies against cancer.
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http://dx.doi.org/10.1186/s12967-020-02662-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731629PMC
December 2020

Mesenchymal stem cell derived-exosomes: a modern approach in translational medicine.

J Transl Med 2020 11 27;18(1):449. Epub 2020 Nov 27.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Shafa St, Ershad Blvd, P.O. BoX: 1138, 57147, Urmia, Iran.

Mesenchymal stem cells (MSCs) have captured great attention in regenerative medicine for over a few decades by virtue of their differentiation capacity, potent immunomodulatory properties, and their ability to be favorably cultured and manipulated. Recent investigations implied that the pleiotropic effects of MSCs is not associated to their ability of differentiation, but rather is mediated by the secretion of soluble paracrine factors. Exosomes, nanoscale extracellular vesicles, are one of these paracrine mediators. Exosomes transfer functional cargos like miRNA and mRNA molecules, peptides, proteins, cytokines and lipids from MSCs to the recipient cells. Exosomes participate in intercellular communication events and contribute to the healing of injured or diseased tissues and organs. Studies reported that exosomes alone are responsible for the therapeutic effects of MSCs in numerous experimental models. Therefore, MSC-derived exosomes can be manipulated and applied to establish a novel cell-free therapeutic approach for treatment of a variety of diseases including heart, kidney, liver, immune and neurological diseases, and cutaneous wound healing. In comparison with their donor cells, MSC-derived exosomes offer more stable entities and diminished safety risks regarding the administration of live cells, e.g. microvasculature occlusion risk. This review discusses the exosome isolation methods invented and utilized in the clinical setting thus far and presents a summary of current information on MSC exosomes in translational medicine.
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http://dx.doi.org/10.1186/s12967-020-02622-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691969PMC
November 2020

Dexosomes as a cell-free vaccine for cancer immunotherapy.

J Exp Clin Cancer Res 2020 Nov 23;39(1):258. Epub 2020 Nov 23.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, P.O. Box: 1138, Shafa St, Ershad Blvd., 57147, Urmia, Iran.

Dendritic cells (DCs) secrete vast quantities of exosomes termed as dexosomes. Dexosomes are symmetric nanoscale heat-stable vesicles that consist of a lipid bilayer displaying a characteristic series of lipid and protein molecules. They include tetraspanins and all established proteins for presenting antigenic material such as the major histocompatibility complex class I/II (MHC I/II) and CD1a, b, c, d proteins and CD86 costimulatory molecule. Dexosomes contribute to antigen-specific cellular immune responses by incorporating the MHC proteins with antigen molecules and transferring the antigen-MHC complexes and other associated molecules to naïve DCs. A variety of ex vivo and in vivo studies demonstrated that antigen-loaded dexosomes were able to initiate potent antitumor immunity. Human dexosomes can be easily prepared using monocyte-derived DCs isolated by leukapheresis of peripheral blood and treated ex vivo by cytokines and other factors. The feasibility of implementing dexosomes as therapeutic antitumor vaccines has been verified in two phase I and one phase II clinical trials in malignant melanoma and non small cell lung carcinoma patients. These studies proved the safety of dexosome administration and showed that dexosome vaccines have the capacity to trigger both the adaptive (T lymphocytes) and the innate (natural killer cells) immune cell recalls. In the current review, we will focus on the perspective of utilizing dexosome vaccines in the context of cancer immunotherapy.
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http://dx.doi.org/10.1186/s13046-020-01781-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686678PMC
November 2020

Anti-allergic effects of vitamin E in allergic diseases: An updated review.

Int Immunopharmacol 2021 Jan 19;90:107196. Epub 2020 Nov 19.

Department of Pediatrics, School of Medicines, Hamedan University of Medical Science, Hamedan, Iran.

Allergic diseases are caused by the immune system's response to innocent antigens called allergens. Recent decades have seen a significant increase in the prevalence of allergic diseases worldwide, which has imposed various socio-economic effects in different countries. Various factors, including genetic factors, industrialization, improved hygiene, and climate change contribute to the development of allergic diseases in many parts of the world. Moreover, changes in lifestyle and diet habits play pivotal roles in the prevalence of allergic diseases. Dietary changes caused by decreased intake of antioxidants such as vitamin E lead to the generation of oxidative stress, which is central to the development of allergic diseases. It has been reported in many articles that oxidative stress diverts immune responses to the cells associated with the pathogenesis of allergic diseases. The aim of this short review was to summarize current knowledge about the anti-allergic properties of vitamin E.
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http://dx.doi.org/10.1016/j.intimp.2020.107196DOI Listing
January 2021

Detailed Investigation of Downstream TLR Signaling in the Follicular Cells of Women with Endometriosis.

J Reprod Infertil 2020 Oct-Dec;21(4):231-239

Department of Gynecology and Obstetrics, School of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.

Background: Inflammatory responses within the peritoneal cavity may result in endometrial dysfunction in women with endometriosis. The true causes of this disease remain poorly understood. It is hypothesized that downstream toll-like receptors (TLRs) inflammatory cytokines in response to pathogens may be associated with endometriosis. So, this study was aimed at evaluating the expression of TLRs signaling and endometriosis-associated inflammatory responses.

Methods: Totally, 20 infertile endometriosis patients and 20 normal women undergoing controlled ovarian stimulation were enrolled. The cellular pellet and supernatant were obtained by centrifugation of follicular fluid (FF). Evaluation of TLRs and their signaling pathway gene expression was performed on cellular pellets using quantitative-PCR. The supernatant was used for determination of cytokine protein expression by ELISA. The results are expressed as mean±SEM and a p<0.05 was considered statistically significant.

Results: Quantitative-PCR analysis suggested that TLR1, 5, 6, 7, 8, 10, MYD88, NF-ĸB, IL-10 and TGF-β genes expression significantly increased in patients compared to the control group (p<0.05). TLR3, 9, INF-β genes expression was significantly lower in endometriosis than control group (p<0.05). There was no significant difference in the expression of TLR2, TLR4, TIRAP, TRIF, TRAM, and IRF3 between two groups. Also, significant increase in the levels of IL-6, IL-8 and MIF protein in FF of endometriosis group was detected in comparison with normal women (p<0.05).

Conclusion: The expression of TLR downstream signaling in the follicular cells can initiate inflammatory responses and changes in the FF cytokine profile which in turn may induce endometriosis and infertility disorder.
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http://dx.doi.org/10.18502/jri.v21i4.4325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648869PMC
November 2020

Orbital cellulitis secondary to giant sino-orbital osteoma: A case report.

Cancer Rep (Hoboken) 2021 Feb 7;4(1):e1296. Epub 2020 Oct 7.

Department of Otolaryngology, Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Although osteoma is a common benign tumor of the paranasal sinuses, its orbital extension is not common. Secondary orbital cellulitis has rarely been reported in association with sino-orbital osteoma.

Case: A 30-year-old woman presented with left side proptosis, orbital pain and inflammation. Orbital CT scan showed a well-defined giant osteoma in the superonasal part of the left orbit originating from the left ethmoidal sinus associated with opacity of the ipsilateral ethmoidal sinus and infiltration of orbital soft tissue. After treatment by systemic antibiotics, osteoma was resected with combined external and endoscopic surgery and the patient recovered uneventfully.

Conclusion: Sino-orbital osteoma may manifest primarily as orbital cellulitis and needs early surgical intervention.
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http://dx.doi.org/10.1002/cnr2.1296DOI Listing
February 2021

Forty Years of Research and Treatment in Immunology and Allergy: In Honor of Professor Reza Farid Hosseini.

Iran J Allergy Asthma Immunol 2020 May 17;19(S1):18-26. Epub 2020 May 17.

School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA, USA 5 Institute of Interventional Allergology and Immunology, Bonn/Cologne, Bonn, Germany AND International Prof. Dr. Alireza Yalda Foundation in Medical Sciences, Bonn/Cologne, Bonn, Germany.

In light of various supports of prodigious figures in the field of immunology and allergy, the subject area has been faced a great leap during the last century. The current state of the discipline owes an abundant appreciation for the scholars motivated in escalating the true nature of the science, who left no stone unturned in improving the general common sense and understanding of the human knowledge in general, and immunology and allergy in particular. Professor Reza Farid Hosseini is among the dignitaries who invested his life and energy on weaving the tapestry of the immunology and allergy. He delivered a great deal of influence on the field by his ethical devotion to science and was a significant contributor in the realms of the human immune system. His presence drastically rehabilitated the place of the Immunology in Iran, and the current paper seeks to review the personal and academic life of Professor Reza Farid Hosseini in honor and appreciation for his in-depth involvement in the field. The paper summarizes Professor Farid's childhood, school, and higher education, compilations, and translation of books, his contribution to the research both inside and outside of Iran, and scientific activities of Dr. Farid Hosseini.
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http://dx.doi.org/10.18502/ijaai.v19i(s1.r1).2851DOI Listing
May 2020

Human closed and open apex premolar teeth express different toll-like receptor.

Mol Genet Genomic Med 2020 07 13;8(7):e1268. Epub 2020 May 13.

Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Background: The innate immune activation which promotes inflammation responses in the dental pulp tissue leads to the progression of dentin caries. Accordingly, toll-like receptors (TLRs) are key molecules of the innate immune system that identify pathogen-associated molecular patterns (PAMPs) on microorganisms and may have a critical role in a dental injury. Therefore, this study aimed to investigate the expression of TLR2, TLR3, and TLR4 in the human dental pulp of opened and closed apex teeth.

Methods: Human dental pulps were derived from the healthy opened and closed apex premolar, in which extraction was indicated for orthodontic reasons. The extraction of RNA was performed and the gene expression determined by real-time polymerase chain reaction (RT-PCR). The result from real-time PCR was confirmed using western blot analysis.

Results: Real-time PCR data analysis showed that the expression TLR2 and TLR4 were significantly increased in closed apex premolar teeth compared to open apex teeth, whereas TLR3 expression was not significantly different in these two groups (p < .05).

Conclusion: The results of the present study suggested increased expression of TLR2 and TLR4 by the maturation of the apex, which may be due to the presence of microorganisms in the normal or destructed dental pulp tissue. Thus, identifying the expression of TLRs molecules in dental pulp tissue helps to develop a deeper knowledge of the immune responses in the oral cavity.
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http://dx.doi.org/10.1002/mgg3.1268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336733PMC
July 2020

Macular Optical Coherence Tomography Angiography in Nephropathic Patients with Diabetic Retinopathy in Iran: A Prospective Case-Control Study.

Ophthalmol Ther 2020 Mar 19;9(1):139-148. Epub 2020 Feb 19.

Department of Ophthalmology, Bu Ali Sina Hospital, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Diabetic macular ischemia (DMI) is an important category of diabetic retinopathy (DR) which leads to severe visual loss. Clinically, it is defined by an enlargement of the foveal avascular zone (FAZ) that can be detected by optical coherence tomography angiography (OCTA). Studies have described a relationship between renal disease and these changes in FAZ area. The aim of this study was to compare disturbances in FAZ area in diabetic patients with or without overt nephropathy.

Methods: Following approval of the ethics committee, we examined diabetic patients with retinopathy. Patients were divided into two groups of DR, namely, with overt nephropathy and without overt nephropathy. The FAZ area was measured using OCTA. A P value of < 0.05 was considered to be statistically significant.

Result: A total of 46 patients (78 eyes) were enrolled in this study. All eyes with DR showed significant changes in FAZ area, but the sizes of the FAZ area were larger in both the superficial and deep layers in patients with clinical albuminuria than in those with no microalbuminuria (P = 0.007 and P = 0.002, respectively).

Conclusion: These results demonstrate that OCTA provides highly detailed information on retinal microvasculature and that it is a reliable modality to assess DR progression in patients with nephropathy. They also show that renal impairment as a systemic risk factor was associated with enlarged FAZ area in DM.
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http://dx.doi.org/10.1007/s40123-020-00236-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054472PMC
March 2020

Initial Evidences of Salt and Pepper Retinal Lesions (SPRL) in Patients with Intestinal Protozoan Infections in Iran.

Infect Disord Drug Targets 2021 ;21(1):60-67

Toxoplasmosis Research Center, Department of Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: It is made clear that salt and pepper retinal lesion (SPRL) has subsequently associated with the infection with Giardia lamblia (G. lamblia). However, little is known regarding the prevalence of SPRL among patients suffered from parasitic infections in the world.

Objective: This study aimed to determine the prevalence of SPRL among patients with intestinal protozoan infections, for the first time, in Sari, northern Iran.

Methods: In this case-control study, a total of 150 subjects participated: 75 were in the patients group diagnosed to have an intestinal parasite and 75 in the control group without any intestinal infection. Fecal samples were obtained from all participants and examined with wet mount and formalin-ether methods. The retina of both groups was examined by an ophthalmologist.

Results: Overall, salt and pepper retinal changes were diagnosed in 12 (16 %) patients with at least one parasitic infection (7 females and 5 males). G. lamblia was diagnosed in 6 subjects (50%), Blastocystis hominis in 5 (41.6%), and Entamoeba coli in 1 (8.3 %). Most of the patients (58.3%) had a mild infection. Bilateral retinal involvement was observed in 75% of the patients. Furthermore, macula involvement was observed in 91.7 % with SPRL.

Conclusion: Our findings indicated the relatively high prevalence of SPRL in subjects with giardiasis and blastocystosis. It can be concluded that not only G. lamblia but also B. hominis can cause SPRL in Sari, Iran. Further studies are needed to find other etiologic parasites able to cause retinal damages.
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http://dx.doi.org/10.2174/1871526520666200106124604DOI Listing
January 2021

Ocular abnormalities in beta thalassemia patients: prevalence, impact, and management strategies.

Int Ophthalmol 2020 Feb 10;40(2):511-527. Epub 2019 Oct 10.

Department of Psychiatric Nursing and Management, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Beta thalassemia (β-thalassemia) is a hereditary disease caused by defective globin synthesis and can be classified into three categories of minor (β-TMi), intermedia (β-TI), and major (β-TM) thalassemia. The aim of our study is to investigate the effects of β-thalassemia and its treatment methods on different parts of the eye and how early-diagnostic methods of ocular complications in this disorder would prevent further ocular complications in these patients by immediate treatment and diet change.

Methods: We developed a search strategy using a combination of the words Beta thalassemia, Ocular abnormalities, Iron overload, chelation therapy to identify all articles from PubMed, Web of Science, Scopus, and Google Scholar up to December 2018. To find more articles and to ensure that databases were thoroughly searched, the reference lists of selected articles were also reviewed.

Results: Complications such as retinopathy, crystalline lens opacification, color vision deficiency, nyctalopia, depressed visual field, reduced visual acuity, reduced contrast sensitivity, amplitude reduction in a-wave and b-wave in Electroretinography (ERG), and decrease in the Arden ratio in Electrooculography (EOG) have all been reported in β-thalassemia patients undergoing chelation therapy.

Conclusion: Ocular problems due to β-thalassemia may be a result of anemia, iron overload in the body tissue, side effects of iron chelators, and the complications of orbital bone marrow expansion.
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http://dx.doi.org/10.1007/s10792-019-01189-3DOI Listing
February 2020

A Biographical History of Some Iranian Pioneers in Medical Immunology and Allergy.

Arch Iran Med 2019 06 1;22(6):344-352. Epub 2019 Jun 1.

Department of Immunology and Allergy, Mashhad University of Medical Sciences, Mashhad, Iran.

The oldest literature that mentioned the immunity was related to the plague of Athens in 430 BC. The germ theory had more influence on the description of the discrimination between self and non-self which is the core concept of immunology. Allergic diseases were known from 2,000 years ago while Rhazes wrote the first medical monograph about seasonal allergic rhinitis. In Iran, Dr. Mohammad Kermanshahi introduced the basic concepts of serology in 1900. The first Department of Serology was established at Tehran University, Faculty of Medicine in 1951 by Prof. Dr. Hassan Mirdamadi. After that, immunology entered into the cellular and molecular period. Prof. Mohammad Ali Maleki established the first Iranian Society of Allergy and then Prof. Abolhassan Farhoodi found the first Department of Clinical Immunology and Allergy at Tehran University. In this paper, we review the role of famous Iranian scientists and physicians in the progress of modern immunology and allergy from a historical perspective.
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June 2019

Local temperature versus system temperature in a simulation experiment containing water molecules.

Phys Chem Chem Phys 2019 Jun 5;21(24):12961-12967. Epub 2019 Jun 5.

Department of Chemistry, Surface Chemistry Research Laboratory, Iran University of Science and Technology, P.O. Box 16846-13114, Tehran, Iran.

Water models are commonly used in simulation experiments containing water molecules. However, the geography, electrical properties, and non-bonded interaction parameters provided by these models do not completely fit the experimental data of water molecules. Therefore, these models cannot reproduce the real physical properties of water. We argue that during the simulation experiment, the faults in a water model can cause the water molecules to experience a local temperature that is different from the system temperature. Hence, the calculated physical properties should be related to the local temperature rather than to the system temperature. We have derived a new relation between the temperature and the self-diffusion coefficient of water. We proposed the use of the self-diffusion coefficient of water calculated from the trajectory for obtaining the local temperature in a simulation experiment. This approach was applied to a TIP3P water model. We carried out a series of molecular dynamics simulations of water molecules by this model and plotted the calculated density versus the calculated local temperature. This plot shows a maximum for water density. We also performed another series of MD simulation experiments and plotted the calculated surface tension of water obtained from the literature versus the calculated local temperature. The obtained plot was very close to the experimental plot and predicted a value of 652 K for the critical temperature of water.
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http://dx.doi.org/10.1039/c9cp01372eDOI Listing
June 2019

Mapping and monitoring of the structure and function of rangeland ecosystems in central Zagros, Iran.

Environ Monit Assess 2018 Oct 22;190(11):662. Epub 2018 Oct 22.

Department of Natural Resources, Isfahan University of Technology, Isfahan, 841568311, Iran.

This study sought to investigate the feasibility of using field data and remote sensing structural and functional indices in the evaluation and monitoring of semi-steppe rangelands of Isfahan Province, Iran. The study area was first divided into 40 sub-catchments, and rangeland conditions in each sub-catchment were classified into three classes using the four-factor method (FFM). Landsat TM and OLI images for 1987 and 2015 were obtained, and the normalized difference vegetation index (NDVI) was calculated. The structure of the area was evaluated using landscape function analysis (LFA) and rangeland landscape metrics. Rangeland function was also assessed and statistically compared using LFA and the leakiness index (LI). In order to clarify the effects of climate and management on rangeland function, changes in the standardized precipitation index (SPI) were computed and monitored at different intervals. The results indicated the reduction of structural indices, rangeland conditions, and patch sizes over time. Structural metrics suggested the fragmentation of the rangelands with 40-60% canopy cover and the development of rangelands with 0-20%. The structural changes affected rangeland function, and thus reduced the functions of the studied sub-catchments over the 28-year period (p < 0.05). The trend of SPI revealed several periods of drought with different intensities and durations. Reduced precipitation caused structural changes and further decreased function in 2015. According to the obtained results, the combined field-based and remotely sensed approach applied in this research can be used to assess and monitor the functionality and structure of semi-steppe rangeland ecosystems at sub-catchment scale.
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http://dx.doi.org/10.1007/s10661-018-7005-8DOI Listing
October 2018

Targeted Co-Delivery of Docetaxel and cMET siRNA for Treatment of Mucin1 Overexpressing Breast Cancer Cells.

Adv Pharm Bull 2018 Aug 29;8(3):383-393. Epub 2018 Aug 29.

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

Targeted treatment of breast cancer through combination of chemotherapeutic agents and siRNA had been drawing much attention in recent researches. This study was carried out to evaluate mucin1 aptamer-conjugated chitosan nanoparticles containing docetaxel and cMET siRNA on SKBR3 cells. Nano-drugs were characterized by transmission electron microscope, Zetasizer and loading efficiency calculation. siRNA entrapment onto nanoparticles, stability of siRNA-loaded nanoparticles and conjugation of mucin1 aptamer to nanoparticles were evaluated via separate electrophoresis. Cellular uptake of the targeted nanoparticles was evaluated through GFP-plasmid expression in mucin1+ SKBR3 vs. mucin1- CHO cells. Protein expression, cell viability and gene expression were assessed by Western Blotting, MTT assay, and Quantitative Real Time-PCR, respectively. Characterization of nano-drugs represented the ideal size (110.5± 3.9 nm), zeta potential (11.6± 0.8 mV), and loading efficiency of 90.7% and 88.3% for siRNA and docetaxel, respectively. Different gel electrophoresis affirmed the conjugation of aptamers to nanoparticles and entrapment of siRNA onto nanoparticles. Increased cellular uptake of aptamer-conjugated nanoparticles was confirmed by GFP expression. cMET gene silencing was confirmed by Western Blotting. The significant (p ≤0.0001) impact of combination targeted therapy vs. control on cell viability was shown. Results of Quantitative Real Time-PCR represented a remarkably decreased (p ≤0.0001) expression of the studied genes involving in tumorigenicity, metastasis, invasion, and angiogenesis (STAT3, IL8, MMP2, MMP9, and VEGF) by targeted combination treatment vs. control. The mucin1 aptamer-conjugated chitosan nanoparticles, containing docetaxel and cMET siRNA, is suggested for treatment of mucin1 metastatic breast cancer cells. However, further studies should be conducted on animal models.
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http://dx.doi.org/10.15171/apb.2018.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156474PMC
August 2018