Ticagrelor reduces doxorubicin-induced pyroptosis of rat cardiomyocytes by targeting GSK-3β/caspase-1

Doxorubicin (Dox) is a widely used clinical drug whose cardiotoxicity cannot be ignored. Pyroptosis (inflammatory cell death) has gradually gained attention in the context of Dox-induced cardiotoxicity. In addition to the inhibition of platelet activation by ticagrelor, little is known about its other pharmacological effects. Glycogen synthase kinase 3β (GSK-3β) has been shown to contribute to the pathological process of pyroptosis, but whether it is related to the potential role of ticagrelor is unclear. In this study, we investigated the effects of ticagrelor on Dox-induced pyroptosis in cardiomyocytes. Rats were treated with ticagrelor (7.5 mg/kg, i.g.) 1 h before intravenous injection of Dox (2.5 mg/kg), once every 3 days, six times in total. Hearts were collected for histochemical analysis and western blot detection 8 weeks after the last administration. Ticagrelor was shown to significantly improve cardiac function by inhibiting GSK-3β/caspase-1/GSDMD activation. In vitro experiments were conducted using rat cardiac myocytes (RCMs) and rat embryonic cardiac-derived H9c2 cells. Pretreatment with ticagrelor (10 μm) significantly inhibited Dox (1 μm)-induced hypertrophy and reversed the upregulation of GSDMD-NT expression. We showed that ticagrelor suppressed the activation of Akt caused by Dox in the heart tissue as well as in RCMs/H9c2 cells caused by Dox. When GSK-3β expression was absent in H9c2 cells, the inhibitory effect of ticagrelor on Dox-induced caspase-1/GSDMD activation was weakened. These data showed that ticagrelor reduced Dox-induced pyroptosis in rat cardiomyocytes by targeting GSK-3β/caspase-1

The preoperative platelet to neutrophil ratio and lymphocyte to monocyte ratio are superior prognostic indicators compared with other inflammatory biomarkers in ovarian cancer

BackgroundPrevious studies have suggested that the ratios of immune-inflammatory cells could serve as prognostic indicators in ovarian cancer. However, which of these is the superior prognostic indicator in ovarian cancer remains unknown. In addition, studies on the prognostic value of the platelet to neutrophil ratio (PNR) in ovarian cancer are still limited.MethodsA cohort of 991 ovarian cancer patients was analyzed in the present study. Receiver operator characteristic (ROC) curves were utilized to choose the optimal cut-off values of inflammatory biomarkers such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and PNR. The correlation of inflammatory biomarkers with overall survival (OS) and relapse-free survival (RFS) was investigated by Kaplan-Meier methods and log-rank test, followed by Cox regression analyses.ResultsKaplan-Meier curves suggested that LMR<3.39, PLR≥181.46, and PNR≥49.20 had obvious associations with worse RFS (P<0.001, P=0.018, P<0.001). Multivariate analysis suggested that LMR (≥3.39 vs. <3.39) (P=0.042, HR=0.810, 95% CI=0.661-0.992) and PNR (≥49.20 vs. <49.20) (P=0.004, HR=1.351, 95% CI=1.103-1.656) were independent prognostic indicators of poor RFS. In addition, Kaplan-Meier curves indicated that PLR≥182.23 was significantly correlated with worse OS (P=0.039).ConclusionTaken together, PNR and LMR are superior prognostic indicators compared with NLR, PLR, and SII in patients with ovarian cancer

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte

From BASE-ASIA Toward 7-SEAS: A Satellite-Surface Perspective of Boreal Spring Biomass-Burning Aerosols and Clouds in Southeast Asia

In this paper, we present recent field studies conducted by NASA's SMART-COMMIT (and ACHIEVE, to be operated in 2013) mobile laboratories, jointly with distributed ground-based networks (e.g., AERONET, http://aeronet.gsfc.nasa.gov/ and MPLNET, http://mplnet.gsfc.nasa.gov/) and other contributing instruments over northern Southeast Asia. These three mobile laboratories, collectively called SMARTLabs (cf. http://smartlabs.gsfc.nasa.gov/, Surface-based Mobile Atmospheric Research & Testbed Laboratories) comprise a suite of surface remote sensing and in-situ instruments that are pivotal in providing high spectral and temporal measurements, complementing the collocated spatial observations from various Earth Observing System (EOS) satellites. A satellite-surface perspective and scientific findings, drawn from the BASE-ASIA (2006) field deployment as well as a series of ongoing 7-SEAS (2010-13) field activities over northern Southeast Asia are summarized, concerning (i) regional properties of aerosols from satellite and in situ measurements, (ii) cloud properties from remote sensing and surface observations, (iii) vertical distribution of aerosols and clouds, and (iv) regional aerosol radiative effects and impact assessment. The aerosol burden over Southeast Asia in boreal spring, attributed to biomass burning, exhibits highly consistent spatial and temporal distribution patterns, with major variability arising from changes in the magnitude of the aerosol loading mediated by processes ranging from large-scale climate factors to diurnal meteorological events. Downwind from the source regions, the tightly coupled-aerosolecloud system provides a unique, natural laboratory for further exploring the micro- and macro-scale relationships of the complex interactions. The climatic significance is presented through large-scale anti-correlations between aerosol and precipitation anomalies, showing spatial and seasonal variability, but their precise cause-and-effect relationships remain an open-ended question. To facilitate an improved understanding of the regional aerosol radiative effects, which continue to be one of the largest uncertainties in climate forcing, a joint international effort is required and anticipated to commence in springtime 2013 in northern Southeast Asia

A Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T

We report a search on a sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne-year exposure collected by PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and electrons. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such dark matter into photon final states. In particular, we present the first direct detection limits for an axial-vector (vector) interaction which are the strongest in the mass range from 25 to 45 (35 to 50) keV/c$^2$