Table_1_Enriched environment promotes post-stroke angiogenesis through astrocytic interleukin-17A.DOC

ObjectiveOur previous studies have revealed that the protective effect of an enriched environment (EE) may be linked with astrocyte proliferation and angiogenesis. However, the relationship between astrocytes and angiogenesis under EE conditions still requires further study. The current research examined the neuroprotective effects of EE on angiogenesis in an astrocytic interleukin-17A (IL-17A)-dependent manner following cerebral ischemia/reperfusion (I/R) injury.MethodsA rat model of ischemic stroke based on middle cerebral artery occlusion (MCAO) for 120 min followed by reperfusion was established, after which rats were housed in either EE or standard conditions. A set of behavior tests were conducted, including the modified neurological severity scores (mNSS) and the rotarod test. The infarct volume was evaluated by means of 2,3,5-Triphenyl tetrazolium chloride (TTC) staining. To evaluate the levels of angiogenesis, the protein levels of CD34 were examined by means of immunofluorescence and western blotting, while the protein and mRNA levels of IL-17A, vascular endothelial growth factor (VEGF), and the angiogenesis-associated factors interleukin-6 (IL-6), JAK2, and STAT3 were detected by western blotting and real-time quantitative PCR (RT-qPCR).ResultsWe found that EE promoted functional recovery, reduced infarct volume, and enhanced angiogenesis compared to rats in standard conditions. IL-17A expression in astrocytes was also increased in EE rats. EE treatment increased the levels of microvascular density (MVD) and promoted the expression of CD34, VEGF, IL-6, JAK2, and STAT3 in the penumbra, while the intracerebroventricular injection of the IL-17A-neutralizing antibody in EE rats attenuated EE-mediated functional recovery and angiogenesis.ConclusionOur findings revealed a possible neuroprotective mechanism of astrocytic IL-17A in EE-mediated angiogenesis and functional recovery after I/R injury, which might provide the theoretical basis for EE in clinical practise for stroke patients and open up new ideas for the research on the neural repair mechanism mediated by IL-17A in the recovery phase of stroke.</p

Isofuranodiene, the main volatile constituent of wild celery (<i>Smyrnium olusatrum</i> L.), protects d-galactosamin/lipopolysacchride-induced liver injury in rats

<p>Isofuranodiene is a natural sesquiterpene rich occurring in <i>Smyrnium olusatrum</i>, a forgotten culinary herb which was marginalised after the domestication of the improved form of celery. Our recent data showed that isofuranodiene inhibited the proliferation and induced apoptosis in cancer cells. In this study, we investigated its protective effect on d-galactosamine/lipopolysacchride (GalN/LPS)-induced liver injury in SD rats. Oral administration of isofuranodiene (20 and 50 mg/kg) dramatically inhibited GalN/LPS-induced serum elevation of aspartate aminotransferase, alanine aminotransferase and malondialdehyde levels, and significantly ameliorated liver injury as evidenced by the histological improvement in H&E staining. Furthermore, isofuranodiene treatment significantly inhibited GalN/LPS-induced mRNA expression of IL-1β, IL-6 and inducible nitric oxide synthase in liver tissues. The results from this study showed that isofuranodiene protects GalN/LPS-induced liver injury in SD rats and suggested that it may be a potential functional food ingredient for the prevention and treatment of liver diseases.</p

The drug–herb interaction network (D–H network) for BZ.

<p>BS, <i>P. corylifolia</i> and <i>C. monnieri</i>; BW, <i>P. corylifolia</i> and <i>A. carmichaelii</i>; BWS, <i>P. corylifolia</i>, <i>C. monnieri</i> and <i>A. carmichaelii</i>.</p

Contents of 15 constituents in 7 decoctions.

<p>Contents of 15 constituents in 7 decoctions.</p

The chemical structures of 15 constituents in BZ.

<p>The chemical structures of 15 constituents in BZ.</p

Pharmacokinetic parameters of 5 constituents after single oral administration of BZ in SD rats.

<p>Pharmacokinetic parameters of 5 constituents after single oral administration of BZ in SD rats.</p

LC-MS/MS chromatograms of 15 constituents (A) blank rat plasma sample spiked with 15 standards; (B) blank rat plasma sample; (C) decoction of BZ; (D) rat plasma sample collected after single oral dose of BZ.

<p>LC-MS/MS chromatograms of 15 constituents (A) blank rat plasma sample spiked with 15 standards; (B) blank rat plasma sample; (C) decoction of BZ; (D) rat plasma sample collected after single oral dose of BZ.</p

Plasma concentration-time curves for psoralen, isopsoralen, psoralidin, xanthotoxin, and bergapten in SD rats after single oral administration of BZ.

<p>Plasma concentration-time curves for psoralen, isopsoralen, psoralidin, xanthotoxin, and bergapten in SD rats after single oral administration of BZ.</p

LC-MS/MS method validation for 15 constituents from BZ.

<p>LC-MS/MS method validation for 15 constituents from BZ.</p

Cucurbitacin B Induced ATM-Mediated DNA Damage Causes G2/M Cell Cycle Arrest in a ROS-Dependent Manner

<div><p>Cucurbitacins are a class of triterpenoids widely distributed in plant kingdom with potent anti-cancer activities both <i>in vitro</i> and <i>in vivo</i> by inducing cycle arrest, autophagy, and apoptosis. Cucurbitacin B (Cuc B), could induce S or G2/M cell cycle arrest in cancer cells while the detailed mechanisms remain to be clear. This study was designed to precisely dissect the signaling pathway(s) responsible for Cuc B induced cell cycle arrest in human lung adenocarcinoma epithelial A549 cells. We demonstrated that low concentrations of Cuc B dramatically induced G2/M phase arrest in A549 cells. Cuc B treatment caused DNA double-strand breaks (DSBs) without affecting the signal transducer and activator of transcription 3 (STAT3), the potential molecular target for Cuc B. Cuc B triggers ATM-activated Chk1-Cdc25C-Cdk1, which could be reversed by both ATM siRNA and Chk1 siRNA. Cuc B also triggers ATM-activated p53-14-3-3-σ pathways, which could be reversed by ATM siRNA. Cuc B treatment also led to increased intracellular reactive oxygen species (ROS) formation, which was inhibited by N-acetyl-l-cysteine (NAC) pretreatment. Furthermore, NAC pretreatment inhibited Cuc B induced DNA damage and G2/M phase arrest. Taken together, these results suggested that Cuc B induces DNA damage in A549 cells mediated by increasing intracellular ROS formation, which lead to G2/M cell phase arrest through ATM-activated Chk1-Cdc25C-Cdk1 and p53-14-3-3-σ parallel branches. These observations provide novel mechanisms and potential targets for better understanding of the anti-cancer mechanisms of cucurbitacins.</p></div