PCSK9 Inhibitor Induces a Transient Decrease in Neutrophil-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio in Homozygous/Compound Heterozygous Familial Hypercholesterolemia Patients

Background: Homozygous/compound heterozygous familial hypercholesterolemia (HoFH/cHeFH) is characterized by extremely elevated low-density lipoprotein-cholesterol (LDL-C) levels that have been reported to contribute to a long-term chronic systemic inflammation. The aims of this study are to describe the inflammatory profile of HoFH/cHeFH patients and explore the effect of PCSK9 inhibitor (PCSK9i) on a series of inflammatory biomarkers, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-HDL ratio (MHR), monocyte-lymphocyte ratio (MLR) and mean platelet volume-lymphocyte ratio (MPVLR). Methods: In this prospective cohort study, 21 definitive HoFH/cHeFH on high-intensity statins plus ezetimibe were placed on subcutaneous injections of PCSK9i 450mg every 4 weeks (Q4W). The biochemical parameters and inflammatory profile were analyzed at the day before PCSK9i therapy, 3 months and 6 months after PCSK9i therapy.Results: We found that HoFH/cHeFH on maximum tolerated statin dose plus ezetimibe displayed an elevated lipid and disturbed blood biomarker profile. After 3 months of add-on PCSK9i therapy, a significant reduction of LDL-C was observed. Meanwhile, percentage and count of neutrophils, monocyte counts, MPV, as well as two inflammatory biomarkers, NLR and MLR were reduced. However, at 6-month PCSK9i treatment, NLR and MLR returned to pre-PCSK9i treatment levels.Conclusions: PCSK9i induces a transient decrease in NLR and MLR in HoFH/cHeFH patients. Our results add evidence in evaluating the effects of PCSK9i on systemic inflammation.

The long-term optical activity of the propellers AE Aquarii and AR Scorpii

This analysis of the long-term optical activity of the propellers AE Aqr and AR Sco uses data from the Catalina Real-time Transient Survey, DASCH, and AAVSO. The site and character of the emissions from the phenomena caused by the magnetic field of the white dwarf (WD) vary from system to system. The histogram of intensities of the ensemble of flares of AE Aqr suggests that the long-term activity consists of a large variety of the peak magnitudes of the flares, with the probability of their detection gradually decreasing with increasing intensity. Any increase of activity only leads to an increase of the number of blobs of the transferring matter. We also detected a season with a transient decrease or even a cessation of the mass outflow from the donor to the lobe of the WD. The very strong orbital modulation of AR Sco is most stable in the phases of the extrema of brightness for about a century; its minor changes suggest that the trailing side of the synchrotron-emitting region is more unstable than the leading side.

A transient decrease in mitochondrial activity is required to establish the ganglion cell fate in retina adapted for high acuity vision

SUMMARYAlthough the plan of the retina is well conserved in vertebrates, there are considerable variations in cell type diversity and number, as well as in the organization and properties of the tissue. The high ratios of retinal ganglion cells (RGCs) to cones in primate fovea and bird retinas favor neural circuits essential for high visual acuity and color vision. The role that cell metabolism could play in cell fate decision during embryonic development of the nervous system is still largely unknown. Here, we describe how subtle changes of mitochondrial activity along the pathway converting uncommitted progenitors into newborn RGCs increase the recruitment of RGC-fated progenitors. ATOH7, a proneural protein dedicated to the production of RGCs in vertebrates, activates transcription of the Hes5.3 gene in pre-committed progenitors. The HES5.3 protein, in turn, regulates a transient decrease in mitochondrial activity via the retinoic acid signaling pathway few hours before cell commitment. This metabolic shift lengthens the progression of the ultimate cell cycle and is a necessary step for upregulating Atoh7 and promoting RGC differentiation.GRAPHICAL ABSTRACT