Cryptotanshinone possesses therapeutic effects on ischaemic stroke through regulating STAT5 in a rat model.

CONTEXT: Cryptotanshinone (CT), a lipophilic compound extracted from roots of Salvia miltiorrhiza Bunge (Lamiaceae) (Danshen), has multiple properties in diseases, such as pulmonary fibrosis, lung cancer, and osteoarthritis. Our previous findings suggest that CT plays a protective role in cerebral stroke. However, the molecular mechanisms underlying CT protection in ischaemic stroke remain unclear. OBJECTIVE: This study examines the effect of CT on ischaemic stroke. MATERIALS AND METHODS: We used the middle cerebral artery occlusion (MCAO) rat (Sprague-Dawley rats, 200 ± 20 g, n = 5) model with a sham operation group was treated as negative control. MCAO rats were treated with 15 mg/kg CT using intragastric administration. Moreover, TGF-ß (5 ng/mL) was used to treat MCAO rats as a positive control group. RESULTS: The 50% inhibitory concentration (IC50) of CT on CD4+ cell damage was 485.1 µg/mL, and median effective concentration (EC50) was 485.1 µg/mL. CT attenuates the infarct region in the MCAO model. The percentage of CD4+CD25+FOXP3+ Treg cells in the peripheral blood of the MCAO group was increased with CT treatment. The protein level of FOXP3 and the phosphorylation of STAT5 were recovered in the CD4+CD25+ Treg cells of model group after treated with CT. Importantly, the effects of CT treatment were blocked by treatment with the inhibitor STAT5-IN-1 in CD4+ T cells of the MCAO model. DISCUSSION AND CONCLUSION: Our findings not only enhance the understanding of the mechanisms underlying CT treatment, but also indicate its potential value as a promising agent in the treatment of ischaemic stroke. Further study will be valuable to examine the effects of CT on patients with ischaemic stroke.

Intrinsic decomposition from a single spectral image.

In this paper, we present a spectral intrinsic image decomposition (SIID) model, which is dedicated to resolve a natural scene into its purely independent intrinsic components: illumination, shading, and reflectance. By introducing spectral information, our work can solve many challenging cases, such as scenes with metameric effects, which are hard to tackle for trichromatic intrinsic image decomposition (IID), and thus offers potential benefits to many higher-level vision tasks, e.g., materials classification and recognition, shape-from-shading, and spectral image relighting. A both effective and efficient algorithm is presented to decompose a spectral image into its independent intrinsic components. To facilitate future SIID research, we present a public dataset with ground-truth illumination, shading, reflectance and specularity, and a meaningful error metric, so that the quantitative comparison becomes achievable. The experiments on this dataset and other images demonstrate the accuracy and robustness of the proposed method on diverse scenes, and reveal that more spectral channels indeed facilitate the vision task (i.e., segmentation and recognition).

Oncolytic adenovirus encoding decorin and CD40 ligand inhibits tumor growth and liver metastasis via immune activation in murine colorectal tumor model.

Colorectal cancer (CRC) is the second common cause of cancer mortality worldwide, and it still lacks effective approaches for relapsed and metastatic CRC. Recently, oncolytic virus has been emerged as a promising immune therapeutic strategy. In this study, we develop a novel oncolytic adenovirus, rAd.mDCN.mCD40L, which drive oncolytic activity by telomerase reverse transcriptase promoter (TERTp). rAd.mDCN.mCD40L expressed both mouse genes of decorin (mDCN) and CD40 ligand (mCD40L), and produced effective cytotoxicity in both human and mouse CRC cells. Moreover, oncolytic adenovirus mediated mDCN over-expression inhibited Met expression in vitro. In CT26 subcutaneous tumor model, intratumorally delivery of oncolytic adenoviruses could inhibit tumor growth and liver metastasis, while mDCN and/or mCD40L armed oncolytic adenoviruses produced much more impressive responses. No obvious toxicity was detected in lung, liver and spleen. Moreover, mDCN and/or mCD40L armed oncolytic adenoviruses altered the immune state to activate anti-tumor responses, including increasing CD8+ T effector cells and CD4+ memory T cells, reducing MDSCs and Tregs in peripheral blood. Furthermore, mDCN and/or mCD40L armed oncolytic adenoviruses mediated mDCN and/or mCD40L expression in tumors, and up-regulated Th1 cytokines and reduced Th2 cytokines in tumors, which will be benefit for remodeling tumor microenvironment. Importantly, rAd.mDCN.mCD40L and rAd.mCD40L prevented tumor liver metastasis much more effectively than rAd.Null and rAd.mDCN. Therefore, rAd.mDCN.mCD40L and rAd.mCD40L are promising approaches for CRC therapy.

Construction of Photoinitiator Functionalized Spherical Nanoparticles Enabling Favorable Photoinitiating Activity and Migration Resistance for 3D Printing.

A straight-forward method was exploited to construct a multifunctional hybrid photoinitiator by supporting 2-hydroxy-2-methylpropiophenone (HMPP) onto a nano-silica surface through a chemical reaction between silica and HMPP by using (3-isocyanatopropyl)-triethoxysilane (IPTS) as a bridge, and this was noted as silica-s-HMPP. The novel hybrid-photoinitiator can not only initiate the photopolymerization but also prominently improve the dispersion of nanoparticles in the polyurethane acrylate matrix and enhance the filler-elastomer interfacial interaction, which results in excellent mechanical properties of UV-cured nanocomposites. Furthermore, the amount of extractable residual photoinitiators in the UV-cured system of silica-s-HPMM shows a significant decrease compared with the original HPMM system. Since endowing the silica nanoparticle with photo-initiated performance and fairly lower mobility, it may lead to a reduction in environmental contamination compared to traditional photoinitators. In addition, the hybrid-photoinitiator gives rise to an accurate resolution object with a complex construction and favorable surface morphology, indicating that multifunctional nanosilica particles can be applied in stereolithographic 3D printing.

Cryptotanshinone exhibits therapeutical effects on cerebral stroke through the PI3K/AKT­eNOS signaling pathway.

Cerebral stroke is a kind of acute cerebrovascular disease with high incidence, morbidity and disability. Treatments against various types of cerebral stroke are limited at preventive measurements due to the lack of effective therapeutic method. The present study aimed to investigate the protective effect of cryptotanshinone (CPT) on cerebral stroke, and investigate the possible mechanism involved in order to develop a novel therapy against stoke. The phosphoinositide 3­kinase membrane translocation of cerebral stroke rats pretreated with CPT at various concentrations were measured, as well as the phosphorylation of protein kinase B (AKT) and endothelial nitric oxide synthase (eNOS). Additionally, the expression level of B­cell lymphoma 2 (Bcl­2), Bcl­2­associated X protein (Bax) and vascular endothelial growth factor were also assessed using western blotting and reverse transcription­quantitative polymerase chain reaction. Furthermore, biochemical tests were used to measure the activity of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) in both the cerebral cortex and peripheral blood. As a result, CPT­pretreated rats presented declined phosphoinositide 3­kinase (PI3K) and AKT expression levels, indicating that the PI3K/AKT signaling pathway was inhibited. Increased Bcl­2 and NO levels in both the cerebral cortex and peripheral blood demonstrated the anti­apoptosis and blood vessel protection effect of CPT. Furthermore, increased SOD activity and declined MDA levels demonstrated suppressed lipid peroxidation. In conclusion, CPT exhibited a protective effect against cerebral stroke through inhibition of the PI3K/AKT­eNOS signaling pathway. These results suggested the potential of CPT as a promising agent in the treatment of cerebral stroke.

[Prediction of drug bioavailability by genetic algorithm and artificial neural network].

AIM: To set up an artificial neural network system and optimize by genetic algorithm (GA) to predict drug bioavailability. METHODS: Genetic algorithm was used to optimize weights of the artificial neural network. The optimal solution of the artificial neural network model at a specific condition was obtained using the good search ability of genetic algorithm in order to predict drug bioavailability. Volume, refractivity, lgP(c), hydration, polarizability, E(HOMO) and E(LUMO) are inputs of the drug bioavailability prediction neural network, and its output is average drug bioavailability. RESULTS: The prediction precision of average drug bioavailability of the GA- neural network model is 95.9%. CONCLUSION: This model can be used in the forecasting of drug bioavailability.