Background/Aims: Recent studies have shown that thymoquinone (TQ) exerts protective effects against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats. Nevertheless, there is no published work investigated the effects of TQ on T cell development and biology in animal models exposed to gamma radiation. Therefore, in the present study we focused on determining the effects of TQ on radiation damage in the thymus, radiation-induced T cell imbalance, and on immune dysfunction induced by gamma-rays. Methods: Three groups of rats were used: a control group, a gamma-irradiated group, and a gamma-irradiated group that was orally supplemented with TQ. Serum lipid profiles, malondialdehyde (MDA) levels, and pro-inflammatory cytokine levels were measured to assess gamma irradiation-induced oxidative stress and inflammatory capacity. T cell apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometry analysis. The expression of pro-apoptotic proteins such as Bax and caspase-3, the anti-apoptotic protein Bcl-2, and an exhaustion marker of T cells (PD-1) in CD4⁺ and CD8⁺ T cell populations was evaluated using flow cytometry analysis. The T cell architecture of the thymus gland was evaluated by histological analysis. Results: Exposure to gamma radiation increased triglyceride, cholesterol, LDL-C, MDA, TNF-α and IL-6 levels and decreased HDL-C levels. The altered lipid profile and MDA and pro-inflammatory cytokine (TNF-α and IL-6) levels induced by exposure to gamma radiation were significantly restored in TQ-treated gamma-irradiated rats. Rats exposed to gamma radiation exhibited increased exhaustion of T lymphocytes via down-regulation of Bcl-2 expression and upregulation of PD-1, Bax, and caspase-3 expression, which sensitized these cells to apoptosis. Interestingly, treatment of gamma-irradiated rats with TQ decreased T cell exhaustion and apoptosis by modulating the expression of Bcl-2, PD-1, Bax, and caspase-3. Conclusions: Our results provide evidence for the beneficial effects of TQ as an effective radioprotective candidate that enhances cellular immunity.

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Aging is a biological phenomenon that involves an increase of oxidative stress associated with gradual degradation of the structure and function of the cornea. Gender differences and subsequent deterioration of cornea is an interesting topic, especially yet few data are available concerning the impact of age, especially on the corneal. One hundred male and female Wistar albino rats ages 3, 6, 18, 24, and 30 months (n=10 equal for male and female) were used. At the time interval, cornea were investigated by light and transmission electron microscopy (TEM), immunohistochemistry of caspase 3 (casp3), glial fibrillar acidic protein(GFAP) and CD45 and  flow cytometry of DNA, bcl-2-like protein 4 (BAX), transforming growth factor beta (TGF-β) and Cd45 (lymphocyte common antigen). Light and TEM investigation  revealed apparent deterioration of atrophy of corneal epithelium with vesicular vacuolar degeneration, hyalinization of stromal collagen fibrils and swelling and degeneration of the endothelial lining the descemet's membrane. There was apparent loss of keratocytes within corneal stroma. Immunohistochemistry of casp 3 and CD45 were markedly increased manifesting cell damage. GFAP showed apparent reduction of innervation of corneal stroma and endothelium layer. Flow cytometry of DNA, Bax and TGF revealed increased apoptic cell death of cornea of 30M-old rats. We concluded that aging contributed to an apparent increase of cellular damage of different corneal region associated with alterations of cell markers.

Introduction Breast cancer (BC) cells often develop multiple mechanisms of chemo- and radio-resistance during tumor progression, which is the major reason for the failure of breast cancer therapy. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over their free drug counterparts. Searching for chemo- and radio-sensitizers to overcome such resistance is therefore urgently required. The goal of this study is to evaluate and compare the radio-sensitizer efficacy of amygdalin-folic acid nanoparticles (Amy-F) on MCF-7 and MDA-MB-231 cells. Materials and methods The effects of Amy-F on MCF-7 and MDA-MB-231 cell proliferation and IC50 were assessed using MTT assay. The expression of proteins involved in several mechanisms induced by Amy-F in MCF-7 and MDA-MB-231 cells, including growth inhibition, apoptosis, tumor growth regulators, immuno-modulators, and radio-sensitizing activities were evaluated via flow cytometry and ELISA assay. Results Nanoparticles demonstrated sustained Amy-F release properties and apparent selectivity towards BC cells. Cell-based assays revealed that Amy-F markedly suppresses cancer cell growth and improves radiotherapy (RT) through inducing cell cycle arrest (G1 and sub-G1), and increases apoptosis as well as reduces the proliferation of BC by down-regulating mitogen-activated protein kinases (MAPK/P38), iron level (Fe), nitric oxide (NO), and up-regulating the reactive oxygen species level (ROS). Amy-F has also been shown to suppress the expression of the cluster of differentiation (CD4 and CD80), and interfere with the Transforming growth factor beta (TGF- β)/Interferon-gamma (INF-g)/Interleukin-2 (IL-2)/Interleukin-6 (IL-6)/Vascular endothelial growth factor (VEGF) induced suppression in its signaling hub, while up-regulating natural killer group 2D receptor (NKG2D) and CD8 expression. Conclusions Collectively, the novel Amy-F either alone or in combination with RT abrogated BC proliferation.

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