Publications by authors named "Sepideh Nikfarjam"

6 Publications

  • Page 1 of 1

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

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

J Neurovirol 2021 04 12;27(2):217-227. 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
April 2021

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

---Successful Application of Whole Cell Panning for Isolation of Phage Antibody Fragments Specific to Differentiated Gastric Cancer Cells.

Adv Pharm Bull 2019 Oct 24;9(4):624-631. Epub 2019 Oct 24.

Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Generation of antibodies which potentially discriminate between malignant and healthy cells is an important prerequisite for early diagnosis and treatment of gastric cancer (GC). Comparative analysis of cell surface protein landscape will provide an experimental basis for biomarker discovery, which is essential for targeted molecular therapies. This study aimed to isolate phage-displayed antibody fragments recognizing cell surface proteins, which were differently expressed between two closely related GC cell lines, namely AGS and MKN-45. We selected and screened a semisynthetic phage-scFv library on AGS, MKN-45, and NIH-3T3 cell lines by utilizing a tailored selection scheme that was designed to isolate phagescFvs that not only recognize the differentiated AGS cells but also distinguish them from NIH3T3 fibroblasts and the poorly differentiated MKN-45 cells. After four rounds of subtractive whole cell panning, 14 unique clones were identified by ELISA screening and nucleotide sequencing. For further characterization, we focused on four phage-scFvs with strong signals in screening, and their specificity was confirmed by cell-based ELISA. Furthermore, the selected phage-scFvs were able to specifically stain AGS cells with 38.74% (H1), 11.04% (D11), 76.93% (G11), and 69.03% (D1) in flow cytometry analysis which supported the ability of these phage scFvs in distinguishing AGS from MKN-45 and NIH-3T3 cells. Combined with other proteomic techniques, these phage-scFvs can be applied to membrane proteome analysis and, subsequently, identification of novel tumor-related antigens mediating proliferation and differentiation of cells. Furthermore, such antibody fragments can be exploited for diagnostic purposes as well as targeted drug delivery of GC.
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http://dx.doi.org/10.15171/apb.2019.072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912189PMC
October 2019

Tailoring subtractive cell biopanning to identify diffuse gastric adenocarcinoma-associated antigens via human scFv antibodies.

Immunology 2020 01 8;159(1):96-108. Epub 2019 Nov 8.

Department of Medical Biotechnology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Among various solid tumours, gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Expansion into the peritoneal cavity, which results from dissemination of diffuse cancer cells, is the main cause of mortality in gastric adenocarcinoma patients. Therefore, investigation of putative biomarkers involved in metastasis is prerequisite for GC management. In an effort to discover potential tumour markers associated with peritoneal metastasis of GC, a semi-synthetic human scFv library (Tomlinson I) was used to isolate novel antibody fragments recognizing MKN-45, a poorly differentiated diffuse gastric adenocarcinoma cell line. Four rounds of subtractive selection each consisting of extensive pre-absorption of phage library with NIH-3T3 murine embryonic fibroblasts and AGS (a well-differentiated intestinal gastric adenocarcinoma) cell line were carried out prior to positive selection on MKN-45 target cells. ELISA-based screening of 192 phage-displayed scFv clones indicated 21 high-affinity binders with specific staining of MKN-45 compared with AGS cells. Diversity analysis of the selected phage-scFvs resulted in five distinct sequences with multiple frequency. Further analysis by ELISA and flow cytometry verified three clones that specifically recognized MKN-45 cells. Liquid chromatography-mass spectrometry analysis of the scFv-immunoprecipitated proteins has led to identification of c-Met, HSP90 α and HSP90 β as candidate biomarkers associated with diffuse GC. Immunohistochemistry revealed the capability of purified scFvs to differentiate diffuse and intestinal gastric adenocarcinoma. Taken together, the isolated MKN-45-specific scFv fragments and their cognate antigens would be beneficial in screening and management as well as targeting and therapy of the diffuse gastric adenocarcinoma.
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http://dx.doi.org/10.1111/imm.13129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904653PMC
January 2020