Autophagy Modulates Glioblastoma Cell Sensitivity to Selinexor-mediated XPO1 inhibition.

Background: Selinexor is a selective inhibitor of exportin-1 (XPO1), a key mediator of the nucleocytoplasmic transport for molecules critical to tumor cell survival. Selinexor's lethality is generally associated with the induction of apoptosis, and in some cases, with autophagy-induced apoptosis. We performed this study to determine Selinexor's action in glioblastoma (GBM) cells, which are notoriously resistant to apoptosis.

Neural substrates underlying distinct dual cognitive syndromes in Parkinson's disease.

Background: A dual-syndrome hypothesis, which states the cognitive impairments in Parkinson's disease (PD) are attributable to frontostriatal dopaminergic dysregulation and cortical disturbance-each associated with attention/executive and memory/visuospatial dysfunction, respectively-has been widely accepted. This multisystem contribution also underlies highly heterogeneous progression rate to dementia.

Methods: Nondemented PD patients who underwent [I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([I]FP-CIT) SPECT and neuropsychological examinations were enrolled.

Monocyte/Macrophage-Specific Loss of ARNTL Suppresses Chronic Kidney Disease-Associated Cardiac Impairment.

Defects in Aryl hydrocarbon receptor nuclear translocator-like 1 (ARNTL), a central component of the circadian clock mechanism, may promote or inhibit the induction of inflammation by monocytes/macrophages, with varying effects on different diseases. However, ARNTL's role in monocytes/macrophages under chronic kidney disease (CKD), which presents with systemic inflammation, is unclear. Here, we report that the expression of in monocytes promoted CKD-induced cardiac damage.

ModBind, a Rapid Simulation-Based Predictor of Ligand Binding and Off-Rates.

In rational drug discovery, both free energy of binding and the binding half-life () are important factors in determining the efficacy of drugs. Numerous computational methods have been developed to predict these important properties, many of which rely on molecular dynamics (MD) simulations. While binding free-energy methods (thermodynamic equilibrium predictions) have been well validated and have demonstrated the ability to drive daily synthesis decisions in a commercial drug discovery setting, the prediction of (kinetics predictions) has had limited validation, and predictive methods have largely not been deployed in drug discovery settings.

Comparison of Treatment Outcomes Between First-Line Chemotherapy With or Without Bevacizumab for Advanced Ovarian Clear Cell Carcinoma (Tohoku Gynecologic Cancer Unit: TGCU-RS001A Study).

: The usefulness of bevacizumab (BEV) as first-line chemotherapy for advanced ovarian clear cell carcinoma (CCC) was retrospectively evaluated at Tohoku Gynecologic Cancer Unit institutions. : A total of 81 patients (52 patients without BEV and 29 with BEV) with advanced ovarian CCC who received initial platinum-based chemotherapy were enrolled. We selected 26 patients each without and with BEV according to propensity score matching methods, and compared the platinum-resistant recurrence rate, response rate, progression-free survival (PFS), overall survival (OS), and adverse events between the two groups.