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Abstract Subarachnoid hemorrhage (SAH) is one of the most severe type of cerebral strokes, which can cause multiple cellular changes in the brain leading to neuronal injury and neurological deficits. Specifically, SAH can impair adult neurogenesis in the hippocampal dentate gyrus, thus may affecting poststroke neurological and cognitive recovery. Here, we identified a non-canonical role of milk fat globule epidermal growth factor 8 (MFGE8) in rat brain after experimental SAH, involving a stimulation on adult hippocampal neurogenesis(AHN). Experimental SAH was induced in Sprague-Dawley rats via endovascular perforation, with the in vivo effect of MFGE8 evaluated via the application of recombinant human MFGE8 (rhMFGE8) along with pharmacological interventions, as determined by hemorrhagic grading, neurobehavioral test, and histological and biochemical analyses of neurogenesis related markers. Results: Levels of the endogenous hippocampal MFGE8 protein, integrin-β3 and protein kinase B (p-Akt) were elevated in the SAH relative to control groups, while that of hippocalcin (HPCA) and cyclin D1 showed the opposite change. Intraventricular rhMGFE8 infusion reversed the decrease in doublecortin (DCX) immature neurons in the DG after SAH, along with improved the short/long term neurobehavioral scores. rhMGFE8 treatment elevated the levels of phosphatidylinositol 3-kinase (PI3K), p-Akt, mammalian target of rapamycin (mTOR), CyclinD1, HPCA and DCX in hippocampal lysates, but not that of integrin β3 and Akt, at 24 hr after SAH. Treatment of integrin β3 siRNA, the PI3K selective inhibitor ly294002 or Akt selective inhibitor MK2206 abolished the effects of rhMGFE8 after SAH. In conclusion, MFGE8 is upregulated in the hippocampus in adult rats with reduced granule cell genesis. rhMFGE8 administration can rescue this impaired adult neurogenesis and improve neurobehavioral recovery. Mechanistically, the effect of MFGE8 on hippocampal adult neurogenesis is mediated by the activation of integrin β3/Akt pathway. These findings suggest that exogenous MFGE8 may be of potential therapeutic value in SAH management. Graphical abstract and proposed pathway of rhMFGE8 administration attenuate hippocampal injury by improving neurogenesis in SAH models. SAH caused hippocampal injury and neurogenesis interruption. Administered exogenous MFGE8, recombinant human MFGE8(rhMFGE8), could ameliorate hippocampal injury and improve neurological functions after SAH. Mechanistically, MFGE8 bind to the receptor integrin β3, which activated the PI3K/Akt pathway to increase the mTOR expression, and further promote the expression of cyclin D1, HPCA and DCX. rhMFGE8 could attenuated hippocampal injury by improving neurogenesis after SAH, however, know down integrin β3 or pharmacological inhibited PI3K/Akt by ly294002 or MK2206 reversed the neuro-protective effect of rhMFGE8.

BackgroundNew media changes the dissemination of public health information and misinformation. During a guest appearance on the Today Show, US Representative Michele Bachmann claimed that human papillomavirus (HPV) vaccines could cause “mental retardation”. ObjectiveThe purpose of this study is to explore how new media influences the type of public health information users access, as well as the impact to these platforms after a major controversy. Specifically, this study aims to examine the similarities and differences in the dissemination of news articles related to the HPV vaccination between Google News and Twitter, as well as how the content of news changed after Michele Bachmann’s controversial comment. MethodsThis study used a purposive sampling to draw the first 100 news articles that appeared on Google News and the first 100 articles that appeared on Twitter from August 1-October 31, 2011. Article tone, source, topics, concerns, references, publication date, and interactive features were coded. The intercoder reliability had a total agreement of .90. ResultsResults indicate that 44.0% of the articles (88/200) about the HPV vaccination had a positive tone, 32.5% (65/200) maintained a neutral tone, while 23.5% (47/200) presented a negative tone. Protection against diseases 82.0% (164/200), vaccine eligibility for females 75.5% (151/200), and side effects 59.0% (118/200) were the top three topics covered by these articles. Google News and Twitter articles significantly differed in article tone, source, topics, concerns covered, types of sources referenced in the article, and uses of interactive features. Most notably, topic focus changed from public health information towards political conversation after Bachmann’s comment. Before the comment, the HPV vaccine news talked more often about vaccine dosing (P

A total of twelve previously unreported isoindolin-1-one compounds, erinacenones A–L (1–12), were isolated from liquid cultures of the medicinal fungus Hericium erinaceus. Their structures were elucidated based on spectroscopic data analysis. The absolute configuration of 12 was determined by comparing its optical rotations with values reported in the literature. The most distinctive feature of these compounds is that their nitrogen atoms are connected to different parts of the special structure moieties. Among them, compounds 3 and 4, as well as 10 and 11, are two pairs of isomers differing only by a small change in the position of one double bond. Compounds 4 and 5 were found to show cytotoxic activities, with IC50 values of 24.7 and 18.4 μM, respectively, against MCF-7 cell lines.

Abstract A series of terpenoids (1–17), comprising six new compounds designated bipolariterpenes A-F (1–6) and eleven recognized compounds (7–17), were isolated from the wheat culture of the potato endophytic fungus Bipolaris eleusines. Their structures and stereochemistry were clarified by HRESIMS, NMR, DP4 + probability analyses, and computations for electronic circular dichroism (ECD). All compounds are made up of six meroterpenoids, four sesterterpenes and seven sesquiterpenes. Among them, four sesterterpenes (4, 5, 10, 11) were investigated for their antifungal, antibacterial and cytotoxic properties, and six meroterpenoids (1–3, 7–9) were evaluated for their antifungal properties. The compounds 7, 9, and 10 had substantial antifungal activity against Epidermophyton floccosum at a concentration of 100 µM. No antibacterial and cytotoxic activities were observed. Graphical Abstract

Abstract Oxepinone rings represent one of structurally unusual motifs of natural products and the biosynthesis of oxepinones is not fully understood. 1,5-Seco-vibralactone (3) features an oxepinone motif and is a stable metabolite isolated from mycelial cultures of the mushroom Boreostereum vibrans. Cyclization of 3 forms vibralactone (1) whose β-lactone-fused bicyclic core originates from 4-hydroxybenzoate, yet it remains elusive how 4-hydroxybenzoate is converted to 3 especially for the oxepinone ring construction in the biosynthesis of 1. In this work, using activity-guided fractionation together with proteomic analyses, we identify an NADPH/FAD-dependent monooxygenase VibO as the key enzyme performing a crucial ring-expansive oxygenation on the phenol ring to generate the oxepin-2-one structure of 3. The crystal structure of VibO reveals that it forms a dimeric phenol hydroxylase-like architecture featured with a unique substrate-binding pocket adjacent to the bound FAD. Computational modeling and solution studies provide insight into the likely VibO active site geometry, and suggest possible involvement of a flavin-C4a-OO(H) intermediate.