Ionizing radiation (IR) induces p53-dependent apoptosis in radiosensitive tissues, suggesting that p53 is a determinant of radiation syndromes. In fact, p53-deficient mice survive doses of IR that cause lethal hematopoietic syndrome in wild-type animals. Surprisingly, p53 deficiency results in sensitization of mice to higher doses of IR, causing lethal gastro-intestinal (GI) syndrome. While cells in the crypts of p53-wild-type epithelium undergo prolonged growth arrest after irradiation, continuous cell proliferation ongoing in p53-deficient epithelium correlates with accelerated death of damaged cells followed by rapid destruction of villi and accelerated lethality. p21-deficient mice are also characterized by increased sensitivity to GI syndrome-inducing doses of IR. We conclude that p53/p21-mediated growth arrest plays a protective role in the epithelium of small intestine after severe doses of IR. Pharmacological inhibition of p53 by a small molecule that can rescue from lethal hematopoietic syndrome has no effect on the lethality from gastro-intestinal syndrome, presumably because of a temporary and reversible nature of its action.

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Oxidative stress and mitochondrial dysfunction are considered to be major contributing factors in the development and progression of many neurodegenerative diseases. Naringenin (NAR) is an abundant flavanone in the Citrus genus and has been found to exert antioxidant, anticarcinogenic and antimutagenic effects. However, the potential underlying mechanism of its antioxidant effects remains unclear. In the present study, the authors investigated the antioxidant effect of NAR on neurons in vitro. Neurons isolated from the brains of Sprague-Dawley rats were randomly divided into a control group, model group, NAR-L group, NAR-M group and NAR-H group. The model group received hypoxia and re-oxygenation treatment, and the NAR-L, NAR-M and NAR-H groups received 20, 40 and 80 µM NAR, respectively. The levels of reactive oxygen species (ROS) in each group were detected by chloromethyl-2',7'dichlorodihydro fluorescein diacetate staining, and differences in mitochondrial dysfunction were analyzed through measurement of mitochondrial membrane potential (∆ψm), adenine nucleotide translocase transport activity and adenine nucleotide levels. MTT and flow cytometry assays were also used to analyze cell proliferation and apoptosis, and the effects of NAR on the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway were investigated using small interfering RNA methods. The authors detected an increased accumulation of ROS in the model group, and high-dose NAR could significantly reduce the levels of ROS. Furthermore, NAR could improve mitochondrial dysfunction, as indicated by increased levels of high-energy phosphates, enhanced mitochondrial ANT transport activity and increased mitochondrial membrane potential. Moreover, NAR increased cell viability and decreased the rate of cell apoptosis. NAR also increased the expression of Nrf2 and its downstream target genes. These findings demonstrated that NAR could reduce oxidative stress and improve mitochondrial dysfunction via activation of the Nrf2/ARE signaling pathway in neurons.

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Apoptosis and oxidative stress are considered to be the major factors associated with the development and progression of many ischaemic cerebrovascular diseases. Naringenin (NAR) is an abundant flavanone in citrus plants and has been found to exhibit anti-oxidant, anti-carcinogenic and anti-apoptotic effects. This study aimed to investigate the anti-apoptotic and anti-oxidant effects of naringenin on ischaemic stroke. In vitro, cortical neuron cells isolated from the brains of neonatal Sprague-Dawley rats were randomly divided into control, oxygen and glucose deprivation/reperfusion (OGD/Rep), NAR-L, NAR-M and NAR-H groups. MTT and RT-PCR were used for cell proliferation and apoptosis-related proteins analyses. The effects of NAR on the Nrf2 signalling pathway were investigated using transfection approaches. Differences in mitochondrial dysfunction were analyzed by flow cytometry. In vivo, middle cerebral artery occlusion (MCAO) model was prepared and neurological defects and the brain wet/dry (W/D) ratio were assessed and recorded; apoptosis was measured based on the TUNEL assay. Additionally, biochemical indices were detected both in vitro and in vivo. NAR promoted cortical neuron cell proliferation, inhibited apoptosis and oxidative stress, and regulated the localization of Nrf2 protein (P<.05). Furthermore, silencing and overexpression of Nrf2 affected cortical neuron cell proliferation and apoptosis (P<.05). In vivo, NAR could alleviate cerebral oedema, improve neurological defects, and reduce apoptosis and oxidative stress (P<.05). These findings demonstrated that NAR could reduce apoptosis and oxidative stress and that Nrf2 signalling pathway is involved in this regulatory process. NAR has health-promoting properties because of its anti-apoptotic and anti-oxidant effects in cases of ischaemic stroke.

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Background/Aims: Stroke is a major cerebrovascular disease threatening human health and life with high morbidity, disability and mortality. It is aimed to find effective biomarkers for the early diagnosis on stroke. Methods: The expressions of 17 previously reported strokeassociated miRNAs were measured using quantitative RT-PCR and the expressions of plasma high-sensitivity C reactive protein (hs-CRP) and serum interleukin 6 (IL-6), the proinflammation markers in brain injury, were examined using enzyme-linked immunosorbent assay in 128 acute ischemic stroke (AIS) patients and control group.