Publications by authors named "Sima Heydarzadeh Asl"

4 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

Blockade of HIF-1α and STAT3 by hyaluronate-conjugated TAT-chitosan-SPION nanoparticles loaded with siRNA molecules prevents tumor growth.

Nanomedicine 2021 Mar 3;34:102373. Epub 2021 Mar 3.

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

HIF-1α and STAT3 are two of the critical factors in the growth, proliferation, and metastasis of cancer cells and play a crucial role in inhibiting anti-cancer immune responses. Therefore, we used superparamagnetic iron oxide (SPION) nanoparticles (NPs) coated with thiolated chitosan (ChT) and trimethyl chitosan (TMC) and functionalized with hyaluronate (H) and TAT peptide for delivery of siRNA molecules against STAT3 and HIF-1α to cancer cells both in vivo and in vitro. The results indicated that tumor cell transfection with siRNA-encapsulated NPs robustly inhibited proliferation and migration and induced apoptosis in tumor cells. Furthermore, simultaneous silencing of HIF-1α and STAT3 significantly repressed cancer development in two different tumor types (4T1 breast cancer and CT26 colon cancer) which were associated with upregulation of cytotoxic T lymphocytes and IFN-γ secretion. The findings suggest inhibiting the HIF-1α/STAT3 axis by SPION-TMC-ChT-TAT-H NPs as an effective way to treat cancer.
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http://dx.doi.org/10.1016/j.nano.2021.102373DOI Listing
March 2021

Inhibition of CD73 using folate targeted nanoparticles carrying anti-CD73 siRNA potentiates anticancer efficacy of Dinaciclib.

Life Sci 2020 Oct 26;259:118150. Epub 2020 Jul 26.

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

Conventional therapeutic methods against cancer, including chemotherapy, radiotherapy, surgery, and combination therapy, have exhibited different toxicity levels due to their unspecific mechanism of action. To overcome the challenges facing conventional cancer therapies, newly developed methods are being investigated. Significant levels of specificity, remarkable accumulation at the tumor site, limited side effects, and minimal off-target effects enable the newly synthesized nanoparticles (NPs) to become the preferred drug delivery method in anticancer therapeutic approaches. According to the literature, CD73 has a pivotal role in cancer progression and resistance to chemotherapy and radiotherapy. Therefore, CD73 has attracted considerable attention among scientists to target this molecule. Accordingly, FDA approved CDK inhibitors such as Dinaciclib that blocks CDK1, 2, 5, and 9, and exhibits significant anticancer activity. So in this study, we intended to simultaneously suppress CD73 and CDKs in cancer cells by using the folic acid (FA)-conjugated chitosan-lactate (CL) NPs loaded with anti-CD73 siRNA and Dinaciclib to control tumor progression and metastasis. The results showed that NPs could effectively transfect cancer cells in a FA receptor-dependent manner leading to suppression of proliferation, survival, migration, and metastatic potential. Moreover, the treatment of tumor-bearing mice with this combination strategy robustly inhibited tumor growth and enhanced survival time in mice. These findings imply the high potential of FA-CL NPs loaded with anti-CD73 siRNA and Dinaciclib for use in cancer treatment shortly.
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http://dx.doi.org/10.1016/j.lfs.2020.118150DOI Listing
October 2020

Silencing adenosine A2a receptor enhances dendritic cell-based cancer immunotherapy.

Nanomedicine 2020 10 15;29:102240. Epub 2020 Jun 15.

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

Overexpression of adenosine in the tumor region leads to suppression of various immune cells, particularly T cells through ligation with adenosine 2a receptor (A2aR). In this study, we intended to increase the efficacy of tumor lysate-loaded DC vaccine by silencing the expression of A2aR on T cells through the application of A2aR-specific siRNA-loaded PEG-chitosan-lactate (PCL) nanoparticles (NPs) in the 4T1 breast tumor-bearing mice. Combination therapy by DC vaccine and siRNA-loaded NPs markedly induced tumor regression and increased survival time of mice. These ameliorative effects were partly via downregulation of immunosuppressive cells, increased function of cytotoxic T lymphocytes, and induction of immune-stimulatory cytokines. Moreover, combination therapy could markedly suppress angiogenesis and metastasis processes. These results imply the efficacy of novel combination therapy for the treatment of breast cancer by using A2aR siRNA-loaded NPs and DC vaccine which can be translated into the initial phase of clinical trials in the near future.
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http://dx.doi.org/10.1016/j.nano.2020.102240DOI Listing
October 2020