Identification and validation of a novel prognostic circadian rhythm-related gene signature for stomach adenocarcinoma.

Circadian rhythm genes were reported to be strongly associated with the development and prognosis of circadian rhythm disorders related to stomach adenocarcinoma (STAD), which is one of the most prevalent cancers. This study aimed to identify a circadian rhythm-related gene signature that could help predict STAD outcome. Using bioinformatics analysis approaches, 105 genes were examined in 350 patients with STAD. Overall, six hub-type circadian rhythm-associated genes (GNA11, PER1, SOX14, EZH2, MAGED1, and NR1D1) were identified using univariate and multivariate Cox regression analyses. These genes were then used to build a genetic predictive model, which was further validated using a publicly available dataset (GSE26899). Overall, genes associated with the circadian rhythm were found to be substantially correlated with the characteristics of the STAD patients (grade, sex, and M stage). In addition, the circadian rhythm-related gene signature was significantly associated with the MAPK and Notch signaling pathways, which are known risk factors for poorer STAD outcome. Taken together, these findings suggest that the herein proposed prognostic model based on six circadian rhythm-associated genes may have predictive value and potential application for clinical decision-making and for personalized treatment of STAD.

Chemical Constituents from Mushroom Suillus luteus (Agaricomycetes) and Their Bioactivities.

Wild edible mushrooms are a huge source to discover bioactive natural products. In this work, one new polyprenylphenol derivative, termed 2-geranylgeranyl-1,4-benzenediol 1-O-acetate (1), together with eight known compounds (2-9) were isolated from wild edible mushroom Suillus luteus. The structure of new compound was elucidated by high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance data. The structures of known compounds were elucidated by comparison of their nuclear magnetic resonance data with literature data. Compounds 1-7 exhibited significant 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity with IC50 values ranging from 1.55 ± 0.29 to 19.89 ± 2.28 µM. In addition, compounds 1-7 also showed tyrosinase inhibitory activity with IC50 values ranging from 21.97 ± 3.74 to 66.26 ± 6.85 µM.

Multistep Consolidated Phototherapy Mediated by a NIR-Activated Photosensitizer.

The multifunctional effect of a single molecule for therapeutic functionalities on a single theranostic nanosystem has a great significance to enhance the accuracy of diagnosis and improve the efficacy of therapy. Herein, a biocompatible multistep phototherapeutic system (Ppa-Cy7-PEG-biotin) that contains a photosensitizer pyropheophorbide A (Ppa) with the covalent conjunction of a near-infrared (NIR) cyanine dye (Cy7) was successfully fabricated and functionalized with biotin for flexible specific tumor-targeting phototherapy. These theranostic micelles will disaggregate after NIR irradiation via the photodegradation of cyanine accompanied by the photothermal conversion and the optically controlled release for the restoration of photodynamic function of quenched Ppa. Consecutively, promoted treatments of photosensitive molecules greatly prolonged the tumor retention time and treatment efficiency, having a multistep antitumor effect both in vitro and in vivo. Different from the simple phototherapeutic configurations that only act on the superficial areas of tumors at mild doses, the multistep therapy can be competent for broadly damaging the superficial and deeper regions of tumors at the same dose. Therefore, as opposed to the general combination phototherapeutic approach, this strategy presents a photoactivation-based multistep phototheranostic platform with an enormous potential in enhanced combined phototherapy for cancer.

Suppressive effects of swainsonine on C6 glioma cell in vitro and in vivo.

Swainsonine, an extract from Astragalus membranaceus, is known for its anti-cancer effects and could prevent metastases. In order to investigate the effects and mechanisms of swainsonine in C6 glioma cells, we carry out correlated experiments in vitro and in vivo. After treatment with swainsonine, the effective dose and IC(50) value of swainsonine in the C6 glioma cell were examined using the MTT assay. Cell cycle distribution and apoptotic rates were analyzed using FCM and [Ca(2+)](i) was measured by LSCM. Expressions of p16 and p53 protein were evaluated by immunocytochemical methods. Simultaneously, glioma-bearing rats were administered swainsonine at doses of 2, 4 and 8 mg/kg body wt. The inhibition rate was calculated and pathological sections were observed. The results indicated that the growth of C6 glioma cells is inhibited by swainsonine in vitro, with an IC(50) value within 24h of 0.05 microg/ml. Increases in swainsonine correlate with S phase percentages of 11.3%, 11.6% and 12.4%, respectively. Moreover, the expression of apoptosis inhibiting p53 and p16 protein decreases gradually. Tumor weight in vivo decreased clearly and HE dyeing of tumor tissue showed gray, its texture was soft, with necrosis and hemorrhagic concentrated inward. Swainsonine could inhibit the proliferation of C6 glioma cells in vitro and the growth of C6 glioma in vivo. The mechanisms of swainsonine-induced apoptosis may relate with the expression of apoptosis-related genes and overloading-[Ca(2+)](i)-induced endoplasmic reticulum stress.

Tumor necrosis factor alpha antibody prevents brain damage of rats with acute necrotizing pancreatitis.

AIM: To study the protective effects of tumor necrosis factor alpha (TNFalpha) antibody on pancreatic encephalopathy in rats. METHODS: One hundred and twenty SD rats were randomly divided into normal control group, acute necrotizing pancreatitis group and TNFalpha antibody treated group. Acute hemorrhage necrotizing pancreatitis model in rats was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct. Serum TNFalpha was detected and animals were killed 12 h after drug administration. Changes in content of brain water, MDA and SOD as well as leucocyte adhesion of brain microvessels were measured. RESULTS: In TNFalpha antibody treated group, serum TNFalpha level was decreased. Content of brain water, MDA and SOD as well as leucocyte adhesion were decreased significantly in comparison with those of acute necrotizing pancreatitis group (P<0.05). CONCLUSION: TNFalpha antibody can alleviate the brain damage of rats with acute hemorrhage necrotizing pancreatitis.