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It has been demonstrated that interleukin 24 (IL-24, also called melanoma differentiation associated gene 7) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirus-mediated gene transfer of IL-24 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-24 (ZD55-IL-24) was constructed by insertion of an IL-24 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. ZD55-IL-24 could express substantially more IL-24 than Ad-IL-24 because of replication of the vector. It has been shown that ZD55-IL-24 exerted a strong cytopathic effect and significant apoptosis in tumor cells with p53 dysfunction. Moreover, no cytotoxic and apoptotic effects could be seen in normal cells infected with ZD55-IL-24. Expression of IL-24 did not interfere with viral replication induced by oncolytic adenovirus. Activation of caspase 3 and caspase 9, and induction of bax gene expression, were involved in tumor cell apoptosis induced by ZD55-IL-24. Treatment of established tumors with ZD55-IL-24 showed much stronger antitumor activity than that induced by ONYX-015 or Ad-IL- 24. These data indicated that oncolytic adenovirus expressing IL-24 could exert potential antitumor activity and offer a novel approach to cancer therapy.

Long non-coding RNA (lncRNA) is a new class of regulative non-coding RNA, with a length larger than 200 nucleotides. Recent studies found that there are close relations between disregulative lncRNAs and human tumors. However, the clinical significances are largely unknown. In this study, we investigated the lncRNA-Fer-1-like protein 4 (FER1L4) level in gastric cancer tissues and plasma. The FER1L4 level in human tissues and plasma were measured by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Then, the correlations between the tissue or plasma FER1L4 levels and clinicopathological factors were assessed. A receiver operating characteristic (ROC) curve was constructed for differentiating GC patients from controls. Compared to matched adjacent non-tumorous tissues, FER1L4 expression levels in 91.80 % (56/61) of gastric cancer tissues are significantly decreased. The low FER1L4 level were associated with tumor size (p < 0.001), histologic grade (p = 0.001), general classification (p < 0.001), depth of invasion (p < 0.001), lymphatic metastasis (p < 0.001), distant metastasis (p = 0.003), TNM stage (p < 0.001), vessel or nerve invasion (p < 0.001 or p = 0.003), and serum CA72-4 (p < 0.001). The area under the ROC curve (AUC) was up to 0.778 (p < 0.001) and the sensitivity and specificity were 67.2 and 80.3 %, respectively. Also, plasma FER1L4 was detected by qRT-PCR. Our data show that there was no difference of plasma FER1L4 level between healthy person and preoperative gastric cancer patients, with a sharp decline in 63.9 % (53/83) of gastric cancer patients 2 weeks after surgery (p = 0.028). Taken together, FER1L4 might play a crucial role in human gastric cancer and may be a new potential biomarker for clinical prognosis evaluation.

Renal ischemia-reperfusion (I/R) injury is a common but severe scientific problem. Luteolin has great anti-inflammatory and antioxidant effects. In this study, we studied the effect of luteolin on renal I/R injury in rats. Intragastric administration of luteolin or saline was performed in Sprague-Dawley rats before (40 mg/kg for three days) and after (one day) renal I/R modeling. Kidney and blood samples were harvested to detect the severity of renal injury 24 hours after operation. The results showed that luteolin-treated rats exhibited milder histomorphological changes with lower scores of renal histological lesions; lower blood urea nitrogen and creatinine levels; lower renal malondialdehyde (MDA), 8-oxo-deoxyguanosine (8-OHdG), and myeloperoxidase (MPO) levels; and higher superoxide dismutase (SOD) and catalase (CAT) activities in the kidney. Luteolin attenuated the increased levels of serum and renal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, renal high mobility group box-1 (HMGB1), and nuclear factor kappa β (NF-κB) expression levels in I/R rats. Furthermore, luteolin treatment significantly reduced renal cell apoptosis and endoplasmic reticulum (ER) stress caused by renal I/R injury. In conclusion, luteolin improved renal function in I/R rats by reducing oxidative stress, neutrophil infiltration, inflammation, renal cell apoptosis, and expression of HMGB1 and NF-κB, and ER stress.

Objective. Cytotherapy is an insufficient method for promoting bone repair in steroid-associated osteonecrosis (SAON), and this has been attributed to impairment of the bioactivity of bone marrow-derived stem cells (BMSCs) after pulsed administration of steroids. Cryopreserved autologous bone marrowderived mononuclear cells (BMMNCs), which contain BMSCs, might maintain their bioactivity in vitro. This study sought to investigate the effects of cryopreserved BMMNCs, before steroid administration, on the enhancement of bone repair in an established rabbit model of SAON.Methods. For in vitro study, bone marrow was harvested 4 weeks before SAON induction from the iliac crests of rabbits (n ‫؍‬ 10) to isolate fresh BMMNCs, and the BMMNCs were then cryopreserved for 8 weeks. Both the fresh and the cryopreserved BMMNCs were evaluated for their bioactivity and osteogenic differentiation capacity. In addition, BMMNCs were isolated 2 weeks after SAON induction and subjected to the same evaluations. For in vivo study, cryopreserved BMMNCs were implanted into the bone tunnel during core decompression of the femur (n ‫؍‬ 12 rabbits) after the induction of SAON, and tissue regeneration was evaluated by micro-computed tomography and histologic analyses at 12 weeks postoperation.Results. In vitro, there were no significant differences in the bioactivity or ability to undergo osteogenic differentiation between fresh BMMNCs and cryopreserved BMMNCs, but after SAON induction, both features were decreased significantly. In vivo, the bone mineral density, ratio of bone volume to total volume of bone, and volume and diameter of neovascularization within the bone tunnel were significantly higher in the BMMNC-treated group compared to the nontreated control group at 12 weeks postoperation.Conclusion. Cryopreserved BMMNCs maintained their bioactivity and promoted bone regeneration and neovascularization within the bone tunnel after core decompression in this rabbit model of SAON.

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Excited states in neutron-rich nuclei located south-east of 132 Sn are investigated by shell-model calculations. A new shell-model Hamiltonian is constructed for the present study. The proton-proton and neutron-neutron interactions of the Hamiltonian are obtained through the existing CD-Bonn G matrix results, while the proton-neutron interaction across two major shells is derived from the monopole based universal interaction plus the M3Y spin-orbit force. The present Hamiltonian can reproduce well the experimental data available in this region, including one-neutron separation energies, level energies and the experimental B(E2) values of isomers in 134,136,138 Sn, 130 Cd, and 128 Pd. New isomers are predicted in this region, e.g. in 135 Sn, 131 Cd, 129 Pd, 132,134 In and 130 Ag, in which almost no excited states are known experimentally yet. In the odd-odd 132,134 In and 130 Ag, the predicted very long E2 life-times of the low-lying 5 − states are discussed, demanding more information on the related proton-neutron interaction. The low-lying states of 132 In are discussed in connection with the recently observed γ rays. The predicted 19/2 − isomer in 129 Pd could decay by both electromagnetic transitions and neutron emission with comparable partial life-times, making it a good candidate for neutron radioactivity, a decay mode which is yet to be discovered.