Investigation of the Antiremodeling Effects of Losartan, Mirabegron and Their Combination on the Development of Doxorubicin-Induced Chronic Cardiotoxicity in a Rat Model

Despite the effectiveness of doxorubicin (DOXO) as a chemotherapeutic agent, dose-dependent development of chronic cardiotoxicity limits its application. The angiotensin-II receptor blocker losartan is commonly used to treat cardiac remodeling of various etiologies. The beta-3 adrenergic receptor agonist mirabegron was reported to improve chronic heart failure. Here we investigated the effects of losartan, mirabegron and their combination on the development of DOXO-induced chronic cardiotoxicity. Male Wistar rats were divided into five groups: (i) control; (ii) DOXO-only; (iii) losartan-treated DOXO; (iv) mirabegron-treated DOXO; (v) losartan plus mirabegron-treated DOXO groups. The treatments started 5 weeks after DOXO administration. At week 8, echocardiography was performed. At week 9, left ventricles were prepared for histology, qRT-PCR, and Western blot measurements. Losartan improved diastolic but not systolic dysfunction and ameliorated SERCA2a repression in our DOXO-induced cardiotoxicity model. The DOXO-induced overexpression of Il1 and Il6 was markedly decreased by losartan and mirabegron. Mirabegron and the combination treatment improved systolic and diastolic dysfunction and significantly decreased overexpression of Smad2 and Smad3 in our DOXO-induced cardiotoxicity model. Only mirabegron reduced DOXO-induced cardiac fibrosis significantly. Mirabegron and its combination with losartan seem to be promising therapeutic tools against DOXO-induced chronic cardiotoxicity.Peer reviewe

AN ENERGY RESOLVED, TRANSLATIONALLY COLD MOLECULAR BEAM FOR COLLISIONAL STUDIES

Author Institution: Department of Physics, The Ohio State University, Columbus, OH 43210-1106, USAA translationally cold molecular beam source based on the collisional cooling technique has been developed. Earlier work resulted in a beam with a very high cluster content. To reduce the cluster concentration, the pulsed source of the earlier experiment was replaced with a continuously open orifice and a mechanical chopper. This provided a higher data acquisition rate and made possible the exploration of lower gas pressure regimes. Electrostatic focusing verified that the new beam was made of monomers. This new approach showed a double-peak speed distribution. An important experimental result is that the beam characteristics are very sensitive to the buffer gas pressure. A model for the observed phenomena will be described

AN ENERGY RESOLVED, TRANSLATIONALLY COLD MOLECULAR BEAM FOR COLLISIONAL STUDIES

Author Institution: Department of Physics, The Ohio State University, Columbus, OH 43210-1106, USAWe have been interested for some time in low energy (\ { }1-10 Kelvin) molecular collisions which lead to the formation of quasibond states. In order to circumvent the limitations ordinarily imposed by vapor pressure, we have previously developed and exploited a quasi thermal equilibrium technique, collisional cooling. However, because it is a thermal technique, the thermal average broadens the energy resonances associated with these processes. In order to remove this average, we have developed a time-of-flight system based on a collisional cooling source and a fast see-through valve that produces translationally cold neutral molecule packets. Pulse widths less than 1ms (an energy resolution of less than 10\%) and translational energies down to 8 Kelvin have been achieved. A quadrupole state selector directs the pulses into oriented beams. A microwave Fabry-Perot cavity tuned to the J=1, K=1 inversion line of ammonia and a quadrupole mass spectrometer are used for detection

Measurements of the HDO/H2O Isotopic Ratio in the Asian Summer Monsoon

International audienceThe Asian Summer Monsoon (ASM) is one of the world's largest weather systems, and forms one of the main pathways by which water vapor enters the UTLS. Uplift in the region lofts highly polluted air from South Asia, making the region an important driver of both stratospheric chemistry and the stratospheric radiation budget. Uplifted air tends to be confined by the monsoon anticyclone, but may enter the stratosphere through uplift within the anticyclone, or via large scale shedding events along its edges. We report here on in situ measurements in the monsoon UTLS of water vapor and its isotopic composition (the ratio of HDO/H2O), an important tracer of uplift processes and of convective activity in general. Measurements were made by the Chicago Water Isotope Spectrometer (ChiWIS) in both the StratoClim (2017) and ACCLIP (2022) campaigns, at monsoon center and in monsoon outflow, respectively. We use these measurements to diagnose the importance of overshooting convection in water transport by the Asian monsoon, characterize the extent to which convection-driven water vapor perturbations propagate to higher altitudes and contribute to the overall stratospheric water budget, and explore cirrus properties in the ASM region

Convective influence on UT/LS water vapor from in-situ measurements of water vapor isotopologues

International audienceThe isotopic composition of water vapor provides a novel source of information on the convective origins and life cycle of water in the UT/LS region. The Chicago Water Isotope Instrument (ChiWIS) has now provided a deep catalog of measurements over both the North American and Asian summer monsoons, from both European and American high-altitude aircraft campaigns: StratoClim (Stratospheric and upper tropospheric processes for better climate predictions) in 2017, and ACCLIP (Asian summer monsoon Chemical and CLimate Impact Project in 2021-2022. Isotopic measurements show the importance of deep convection in carrying moisture as lofted ice, but also the strong distinction between the two monsoons, with higher convective influence and more complete sublimation over North America. Convective outflow remnants remain distinct for as long as two weeks and govern the locations of formations of in-situ ‘secondary cirrus’. We show the consistency and power of the complete dataset collected and examples highlighting the utility of isotopic measurements in understanding the life cycle of UT/LS water, including convective inputs, mixing, sedimentation, and sublimation