No abstract

Radiation-induced intestinal injuries (RIII) commonly occur in patients who suffer from pelvic or abdominal cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant, and the radioprotective role of Nrf2 is found in bone marrow, lung, and intestine, etc. Here, we investigated the effect of Nrf2 knockout on radiation-induced intestinal injuries using Nrf2 knockout (Nrf2−/−) mice and wild-type (Nrf2+/+) C57BL/6J mice following 13 Gy abdominal irradiation (ABI). It was found that Nrf2 knockout promoted the survival of irradiated mice, protected the crypt-villus structure of the small intestine, and elevated peripheral blood lymphocyte count and thymus coefficients. The DNA damage of peripheral blood lymphocytes and the apoptosis of intestinal epithelial cells (IECs) of irradiated Nrf2−/− mice were decreased. Furthermore, compared with that of Nrf2+/+ mice, Nrf2 knockout increased the number of Lgr5+ intestinal stem cells (ISCs) and their daughter cells including Ki67+ transient amplifying cells, Villin+ enterocytes, and lysozyme+ Paneth cells. Nuclear factor-κB (NF-κB) was accumulated in the crypt base nuclei of the small intestine, and the mRNA expression of NF-κB target genes Bcl-2, uPA, and Xiap of the small intestine from irradiated Nrf2−/− mice were increased. Collectively, Nrf2 knockout has the protective effect on small intestine damage following abdominal irradiation by prompting the proliferation and differentiation of Lgr5+ intestinal stem cells and activation of NF-κB.

Applying large amounts of potash fertilizer in apple orchards for high apple quality and yield aggravates KCl stress. As a phytoalexin, resveratrol (Res) participates in plant resistance to biotic stress. However, its role in relation to KCl stress has never been reported. Herein we investigated the role of Res in KCl stress response of Malus hupehensis Rehd., a widely used apple rootstock in China which is sensitive to KCl stress. KCl-stressed apple seedlings showed significant wilting phenotype and decline in photosynthetic rate, and the application of 100 μmol Res alleviated KCl stress and maintained photosynthetic capacity. Exogenous Res can strengthen the activities of peroxidase and catalase, thus eliminating reactive oxygen species production induced by KCl stress. Moreover, exogenous Res can decrease the electrolyte leakage by accumulating proline for osmotic balance under KCl stress. Furthermore, exogenous Res application can affect K+/Na+ homeostasis in cytoplasm by enhancing K+ efflux outside the cells, inhibiting Na+ efflux and K+ absorption, and compartmentalizing K+ into vacuoles through regulating the expression of K+ and Na+ transporter genes. These findings provide a theoretical basis for the application of exogenous Res to relieve the KCl stress of apples.

Taraxasterol is an effective component of dandelion that has anti-inflammatory effects and. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice. Eight-week-old CCR9-deficient mice were injected with a collagen II monoclonal antibody cocktail to create a rheumatoid arthritis model. In the experimental group, arthritic model mice were treated with 10 mg/kg taraxasterol once per day for 5 days. Treatment with taraxasterol significantly increased the pain thresholds and reduced the clinical arthritic scores of the mice in the experimental group compared with those of the model group. Furthermore, treatment with taraxasterol significantly suppressed tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and nuclear factor-κB protein expression levels compared with those in the rheumatoid arthritis model mice. Taraxasterol treatment also significantly reduced nitric oxide, prostaglandin E2 and cyclooxygenase-2 levels compared with those in the rheumatoid arthritis model group. These observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice.

Tissue and cell damage caused by ionizing radiation is often highly genotoxic. The swift repair of DNA damage is crucial for the maintenance of genomic stability and normal cell fitness. Long noncoding RNAs (lncRNAs) have been reported to play an important role in many physiological and pathological processes in cells. However, the exact function of lncRNAs in radiation-induced DNA damage has yet to be elucidated. Therefore, this study aimed to analyze the potential role of lncRNAs in radiation-induced DNA damage. We examined the expression profiles of lncRNAs and mRNAs in 293T cells with or without 8 Gy irradiation using high-throughput RNA sequencing. We then performed comprehensive transcriptomic and bioinformatic analyses of these sequencing results. A total of 18,990 lncRNAs and 16,080 mRNAs were detected in all samples. At 24 h post irradiation, 49 lncRNAs and 323 mRNAs were differentially expressed between the irradiation group and the control group. qRT-PCR was used to verify the altered expression of six lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the predicted genes were mainly involved in the histone mRNA metabolic process and Wnt signaling pathways. This study may provide novel insights for the study of lncRNAs in radiation-induced DNA damage.

Correlation between fecal calprotectin (FC) and endoscopic activity assessed by Ulcerative Colitis Endoscopic Index of Severity (UCEIS) in acute severe colitis (ASC) patients was explored to evaluate the predictive value of FC in clinical outcomes. Seventy-one ASC patients were retrospectively evaluated. FC level within 3 days of colonoscopy was measured with ELISA. Demographic and clinical data, laboratory parameters, and medical therapy were documented, and the endoscopic severity of disease was rated by UCEIS. The end points were the rate of failed corticosteroid therapy, colectomy, and mortality. There was significant correlation between UCEIS and FC level (r=0.729, P<0.001), which was superior to CRP, ESR, and hemoglobin. FC level between endoscopic mild activity (UCEIS, 3-4) and endoscopic moderate activity (UCEIS, 5-6), and endoscopic moderate activity (UCEIS, 5-6) and endoscopic severe activity (UCEIS, 7-8) were significantly different. FC levels were associated with different outcomes (failed corticosteroid therapy or surgery); when FC >1672 µg/g, sensitivity and specificity were 80.2 and 66.7%, respectively, in prediction for colectomy using receiver operating characteristics analysis. The results indicated that FC, as a non-invasive indicator, correlates positively with the UCEIS. Baseline FC level predicts clinical outcomes in ASC patients, which make a timely treatment strategy conversion possible after accurately forecasting the likelihood of failure of intravenous steroid therapy.

No abstract

Salinity-alkalinity stress can remarkably affect the growth and yield of apple. Strigolactone (SL) is a class of carotenoid-derived compounds that functions in stress tolerance. However, the effects and mechanism of exogenous SL on the salinity-alkalinity tolerance of apple seedlings remain unclear. Here, we assessed the effect of SL on the salinity-alkalinity stress response of Malus hupehensis seedlings. Results showed that treatment with 100 μM exogenous SL analog (GR24) could effectively alleviate salinity-alkalinity stress with higher chlorophyll content and photosynthetic rate than the apple seedlings without GR24 treatment. The mechanism was also explored: First, exogenous GR24 regulated the expression of Na+/K+ transporter genes and decreased the ratio of Na+/K+ in the cytoplasm to maintain ion homeostasis. Second, exogenous GR24 increased the enzyme activities of superoxide, peroxidase and catalase, thereby eliminating reactive oxygen species production. Third, exogenous GR24 alleviated the high pH stress by regulating the expression of H+-ATPase genes and inducing the production of organic acid. Last, exogenous GR24 application increased endogenous acetic acid, abscisic acid, zeatin riboside, and GA3 contents for co-responding to salinity-alkalinity stress indirectly. This study will provide important theoretical basis for analyzing the mechanism of exogenous GR24 in improving salinity-alkalinity tolerance of apple.