Neda Khosravi - Academia.edu (original) (raw)

Papers by Neda Khosravi

Journal of Controlled Release

Molecules, 2021

Background: Glioma is an aggressive type of brain tumor that originated from neuroglia cells, acc... more Background: Glioma is an aggressive type of brain tumor that originated from neuroglia cells, accounts for about 80% of all malignant brain tumors. Glioma aggressiveness has been associated with extreme cell proliferation, invasion of malignant cells, and resistance to chemotherapies. Due to resistance to common therapies, glioma affected patients’ survival has not been remarkably improved. ZEB2 (SIP1) is a critical transcriptional regulator with various functions during embryonic development and wound healing that has abnormal expression in different malignancies, including brain tumors. ZEB2 overexpression in brain tumors is attributed to an unfavorable state of the malignancy. Therefore, we aimed to investigate some functions of ZEB2 in two different glioblastoma U87 and U373 cell lines. Methods: In this study, we investigated the effect of ZEB2 knocking down on the apoptosis, cell cycle, cytotoxicity, scratch test of the two malignant brain tumor cell lines U87 and U373. Besides...

European Journal of Pharmacology, 2021

Nanog is a major transcription factor related to cellular multipotency that plays important roles... more Nanog is a major transcription factor related to cellular multipotency that plays important roles in the development of tumor cells, drug resistance, migration, and stemness; indicating its great potential as a therapeutic target for various malignancies including colorectal cancer (CRC). Therefore, this study was aimed to evaluate the Nanog suppression effect using small interference RNA (siRNA) combined with 5-fluorouracil (5-FU) on CRC cells. Nanog-overexpressing SW-480 cells were transfected with Nanog si-RNA and treated with 5-FU, in combination or separately. Subsequently, it was observed that Nanog expression was significantly reduced after transfection of SW-480 cells using Nanog siRNA in mRNA and protein levels. Furthermore, Nanog knockdown significantly increased CRC cell sensitivity to 5-FU drug via modulating Bax and Bcl-2 mRNA expression. Also, Nanog knockdown and 5-FU treatment cooperatively decreased the migration and self-renewal ability of SW-480 cells by regulating the expression of relevant genes. Moreover, combination therapy led to cell cycle arrest at the sub-G1 phase in CRC cells. In conclusion, our results indicated that Nanog may play an important role in the drug sensitivity, migration, and self-renewal of CRC cells; suggesting Nanog as a promising target in combination with 5-FU for the development of new therapeutic approaches for CRC.

Frontiers in Oncology, 2020

Tumor microenvironment (TME) is composed of tumor cells and surrounding non-tumor stromal cells, ... more Tumor microenvironment (TME) is composed of tumor cells and surrounding non-tumor stromal cells, mainly including tumor associated macrophages (TAMs), endothelial cells, and carcinoma-associated fibroblasts (CAFs). The TAMs are the major components of non-tumor stromal cells, and play an important role in promoting the occurrence and development of tumors. Macrophages originate from bone marrow hematopoietic stem cells and embryonic yolk sacs. There is close crosstalk between TAMs and tumor cells. With the occurrence of tumors, tumor cells secrete various chemokines to recruit monocytes to infiltrate tumor tissues and further promote their M2-type polarization. Importantly, M2-like TAMs can in turn accelerate tumor growth, promote tumor cell invasion and metastasis, and inhibit immune killing to promote tumor progression. Therefore, targeting TAMs in tumor tissues has become one of the principal strategies in current tumor immunotherapy. Current treatment strategies focus on reducing macrophage infiltration in tumor tissues and reprogramming TAMs to M1like to kill tumors. Although these treatments have had some success, their effects are still limited. This paper mainly summarized the recruitment and polarization of macrophages by tumors, the support of TAMs for the growth of tumors, and the research progress of TAMs targeting tumors, to provide new treatment strategies for tumor immunotherapy.

International Journal of Cancer Management, 2017

Background: Cancer is one of the most significant causes of death. Plants with anti-cancer effect... more Background: Cancer is one of the most significant causes of death. Plants with anti-cancer effects have shown to eliminate tumor cells by the induction of apoptosis. Objectives: The present study aimed at investigating the apoptotic effects of 3 Euphorbia native species (E. microciadia Boiss, E. osyridea Boiss, and E. heteradenia Jaub. & Sp.). Methods: Cell lines with the strongest sensitivity to the extracts including HeLa for E. microciadia, K562 for E. heteradenia, and Fen for E. osyridea were investigated for the effects of the plants' hexane extracts on the induction of apoptosis, according to annexin V/propidium iodide staining by flow cytometry. We used real-time PCR to evaluate the changes in expressions of genes related to the intrinsic and extrinsic apoptosis pathways. Results: Flow cytometry results indicated that 50 µg/mL of all the extracts induced apoptosis in more than 60% of treated cells. Administration of the extracts resulted in increased caspase-3 activity for all treated cell lines. Real-time PCR results showed decreased B-cell lymphoma-2 (Bcl-2) and increased Bax and Fas mRNA levels in cells treated with the extracts. The Bax/Bcl-2 ratio in cells treated with 50µg/mL of E. microciadia was 29.25 ± 12.0 (P < 0.05) and for 100 µg/mL of E. heteradenia. and E. osyridea was 30.2 ± 13.0 (P < 0.05) and 22.2 ± 2.4 (P < 0.001), respectively. Conclusions: The studied plants have shown remarkable apoptosis-inducing effects on tumor cell lines by affecting both the extrinsic and intrinsic apoptosis pathways. Additional studies in terms of their beneficial effects as natural sources of potential anti-cancer agents will be necessary.

Asian Pacific Journal of Cancer Prevention, 2019

Background: Immunomodulatory materials from natural herbs and the characterization of their immun... more Background: Immunomodulatory materials from natural herbs and the characterization of their immune enhancement effects may have tremendous potential as cancer treatment. The aim of the present study was to investigate the apoptosis-inducing activities of Euphorbia hebecarpa Boiss and Euphorbia petiolata Banks & Sol. plant extracts and their effects on cytokine secretion by lymphocytes. Materials and Methods: We assessed the apoptosis-inducing effect of the plants' hexane extracts on previously determined sensitive cell lines (HeLa for E. hebecarpa and K562 for E. petiolata) by flow cytometry and measurement of caspase 3 activation. The apoptosis-related gene expressions were examined by real-time PCR. The effects of the extracts on lymphocyte proliferation and cytokine secretion were examined. Results: Flow cytometry analysis showed that the inhibitory effect of the extracts on tumor cell growth was due to cell apoptosis. The plant extracts at the 100 µg/ml dose induced apoptosis in HeLa (98.5 ± 0.1%) and K562 (57.7 ± 1.9%) cells. The extracts increased caspase 3 activation (≈2-fold>control). Real-time PCR showed Fas and Bax gene upregulation and Bcl-2 downregulation, which resulted in an increased Bax/Bcl-2 expression ratio. The extracts increased lymphocyte proliferation and increased levels of IFN-γ production in the presence and absence of mitogen (p < 0.05). They significantly increased IL-4 and decreased IL-10 secretion by mitogen-stimulated lymphocytes. E. hebecarpa also increased IL-17 release. Conclusion: These results have shown that both extracts possess antitumor activity by inducing apoptosis, possibly through both intrinsic and extrinsic pathways. In addition, they induced secretion of different T helper subset related cytokines that are effective in the immune response against cancer.

Seminars in Cancer Biology, 2019

Interactions between immune checkpoints (ICs) and their ligands negatively regulate T cell activa... more Interactions between immune checkpoints (ICs) and their ligands negatively regulate T cell activation pathways involved in physiological immune responses against specific antigens. ICs and their ligands are frequently upregulated in the tumor microenvironment (TME) of various malignancies, and they represent significant barriers for induction of effective anti-tumor immune responses. Several IC inhibitors (ICIs) have been developed, with some currently in clinical trials and others being approved for the treatment of different cancers. However, tumor 2 cells are able to counteract the activity of ICIs and can commission additional inhibitory pathways via expression of other ICs/ligands within the TME. This review discusses the expression of various ICs/ligands in the TME and their impact on tumor immune evasion. Additionally, we discuss various regulatory mechanisms, including genetic and epigenetic, and other modulatory factors including hypoxia and the presence of immunosuppressive populations in the TME, which result in upregulation of ICs in various cancers. Moreover, we discuss the prognostic significance of ICs and their ligands, and the potential strategies to enhance treatment responses to ICIs. This review aims to advance our current knowledge on the role of ICs in the TME and the clinical benefits of targeting them.

Pharmaceutical Biology, 2014

Euphorbia is an important Euphorbiaceae genus that is traditionally being used for various infect... more Euphorbia is an important Euphorbiaceae genus that is traditionally being used for various infections, inflammation, and cancer. The present study investigated the possible in vitro immunomodulatory effect of three species of Euphorbia genus including Euphorbia microciadia Boiss, Euphorbia osyridea Boiss, and Euphorbia heteradenia Jaub. &amp;amp;amp;amp;amp;amp; Sp. on lymphocyte activation and cytokine secretion. Human lymphocytes were cultured in the presence of various concentrations (0.1-200 µg/ml) of the butanol/hexane extracts of the plants in the presence or absence of phytohemmagglutinin (PHA). The activation of lymphocytes after 48 h was determined by a proliferation assay. The release of T cell cytokines was studied to determine the dominant T cell subsets involved in the immune response. All three plant extracts increased the proliferation of PHA-treated lymphocytes (maximum; 132% of control). Extract treatment of lymphocytes in the absence of PHA resulted in an increased proliferation of the cells indicating their lymphocyte mitogenic activity (maximum at 10 µg/ml E. microciadia extract; 494.5 ± 42.2% of control, p &amp;amp;amp;amp;amp;lt; 0.01). The extracts of E. microciadia and E. osyridea could increase IL-4 and IL-10 secretion but not IFN-γ production showing their capacity to deviate immune response toward a Th2 pattern. Euphorbia heteradenia did not change the release of IL-4 and IFN-γ cytokines but increased IL-10 production. The three extracts stimulated lymphocytes to produce IL-17 which showed their possible effects on Th17 cells activation. The studied extracts had the ability to modulate T cell responses suggesting their possible beneficial effects on immune host defense.

Background: Mercury (Hg) is considered a global pollutant because Hg 0 which is the predominant f... more Background: Mercury (Hg) is considered a global pollutant because Hg 0 which is the predominant form of atmospheric Hg resides in the atmosphere for as long as 0.5 to 2 years. Mercury has many negative effects on the reproductive, respiratory, and immune systems. Methods: In this study, 24 Caspian lampreys (Caspiomyzon wagneri) were transported to the university laboratory and then stored in-20 o C until they were dissected. The liver, muscle, skin, ovaries, and testes were all dissected out. All samples were freeze-dried and ground by a mortar and pestle into powder. The specimens were analyzed by a Leco AMA254 mercury analyzer. Results: The order of mercury concentration in the lamprey tissues was as follows: Muscle > ovaries > liver > skin > testes. The mean values of mercury in muscle and testes were 192.25 ± 7.10 and 21.42 ± 1.48 Hg ng/g dry weight, respectively. There were no significant differences (N = 24) between the sexes in the Hg level of most tissues except for gonads. Discussion: A comparison with some ammocoetes of jawless fishes shows a 10 times less concentration than other records. This difference probably is due to non-parasitic behavior and use of various sources of nutrition in other species. Conclusion: In comparison of other kind of sea lamprey, due to detritivore habits of Caspian lamprey on a very specific part of food web (non-live food only in the sea floor), the supposed species can introduce as a special indicator of mercury and heavy metal levels in the aquatic ecosystem.