Anesthesia, Blood Pressure, and Socioeconomic Status in Endovascular Thrombectomy for Acute Stroke: A Single Center Retrospective Case Cohort.

Introduction: Mechanical thrombectomy (MT) is standard for acute ischemic stroke (AIS), with early studies suggesting that general anesthesia (GA) is associated with worse outcomes than monitored anesthesia care (MAC). Socioeconomic deprivation is also a risk factor for worse AIS outcomes. With improvements in MT and blood pressure (BP) management, it remains unclear if GA or socioeconomic deprivation are risk factors for worse outcomes after MT.

Rational design of the microtubule-targeting anti-breast cancer drug EM015.

We studied in silico docking of noscapine onto tubulin, combined with calculations of surface charge, pi-pi, van der Waals, and hydrogen bonding interactions, to rationally design a new compound, EM015. This tubulin-binding semisynthetic compound is a selective and potent anti-breast cancer agent and displays a 20-fold lower IC(50) against many tumor cells compared with our founding compound, (S)-6,7-dimethoxy-3-((R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro[1,3]-dioxolo-[4,5-g]isoquinolin-5-yl)isobenzo-furan-1(3H)-one (noscapine). Furthermore, EM015 is also effective against a variety of drug-resistant cells.

Akt phosphorylates acinus and inhibits its proteolytic cleavage, preventing chromatin condensation.

Akt promotes cell survival by phosphorylating and inhibiting components of the intrinsic cell death machinery. Akt translocates into the nucleus upon exposure of cells to survival factors, but little is known about its functions in the nucleus. Here, we show that acinus, a nuclear factor required for apoptotic chromatin condensation, is a direct target of Akt.

Attachment and tension in the spindle assembly checkpoint.

Faithful transmission of chromosomes during mitosis is ensured by the spindle assembly checkpoint. This molecular safeguard examines whether prerequisites for chromosome segregation have been satisfied and thereby determines whether to execute or to delay chromosome segregation. Only when all the chromosomes are attached by kinetochore microtubules from two opposite spindle poles and proper tension is placed on the paired kinetochores does anaphase take place, allowing the physical splitting of sister chromatids.

Paclitaxel-resistant human ovarian cancer cells undergo c-Jun NH2-terminal kinase-mediated apoptosis in response to noscapine.

We have previously discovered the opium alkaloid noscapine as a microtubule interacting agent that binds to tubulin, alters the dynamics of microtubule assembly, and arrests mammalian cells at mitosis (Ye, K., Ke, Y., Keshava, N.