Lysosomal regulation of extracellular vesicle excretion during d-ribose-induced NLRP3 inflammasome activation in podocytes
In this study, we hypothesized that the NLRP3 inflammasome product, IL-1β in response to exogenously administrated and endogenously produced d-ribose stimulation is released via extracellular vesicles including EVs via a sphingolipid-mediated molecular mechanisms controlling lysosome and multivesicular body (MVB) interaction. First, we demonstrated that both endogenous and exogenous d-ribose induced NLRP3 inflammasome activation to produce IL-1β, which was released via EVs in podocytes. Then, we found that colocalization of marker MVB marker VPS16 with IL-1β within podocytes increased upon d-ribose stimulation, which was accompanied by decreased colocalization of lysosome marker Lamp-1 and VPS16, suggesting decrease in MVB inclusion of IL-1β due to reduced lysosome and MVB interaction. All these changes were mimicked and accelerated by lysosome v-ATPase inhibitor, bafilomycin. Moreover, ceramide in podocytes was found elevated upon d-ribose stimulation, and prior treatments of podocyte with acid sphingomyelinase (Asm) inhibitor, amitriptyline, acid ceramidase (AC) inducer, genistein, or AC CRISPR/cas9 activation plasmids were found to decrease d-ribose-induced ceramide accumulation, EVs release and IL-1β secretion due to reduced interactions of lysosome with MVBs. These results suggest that inflammasome-derived products such as IL-1β during d-ribose stimulation are released via EVs, in which lysosomal sphingolipid-mediated regulation of lysosome ...
Authors: Cesaro A, Moscarella E, Gragnano F, Perrotta R, Diana V, Pariggiano I, Concilio C, Alfieri A, Cesaro F, Mercone G, Falato S, Esposito A, Di Girolamo D, Limongelli G, Calabrò P Abstract Introduction: The radial artery is currently the most widely used access site for PCI procedures both acute and stable patient settings. Thanks to advantages in pharmacological therapy as well as in interventional devices, the rate of ischemic complications following PCI has significantly decreased. Nevertheless, this has been counterbalanced by an increased risk of periprocedural and late bleeding event, that can occ...
This report is important to gain more information about corneal perforation clinical presentation in neonates, Investigation, and management.
Publication date: June 2019Source: Pathology - Research and Practice, Volume 215, Issue 6Author(s):
We report a 58-year-old man who presented with perineal nuchal-type fibroma originating in the perirectal region. This tumor was surgically excised; however, the fibrous band from tumor reached into levator ani muscle and was resected incompletely. Continuous follow up is needed even though this tumor is benign.
We present a case of mantle cell lymphoma with the typical phenotype, which transformed to a blastic morphology with loss of expression of CD20, CD5 and BCL2, and gain of CD10 and TdT. In cases presenting with blastic morphology, the use of CD10 and TdT in addition to the usual mantle cell lymphoma markers is essential since cases of mantle cell lymphoma with B-lymphoblastic features may require innovative treatment.
Conclusion: The present study provides a corpus of knowledge considered essential for patients in the self-management of their arthritis. The selection of many items reflects recent emphasis on professional recommendations and the patients’ perspective. Future work should lead to the development of new updated KQs for patients with inflammatory arthritis.
Publication date: April 2019Source: Journal of American Association for Pediatric Ophthalmology and Strabismus, Volume 23, Issue 2Author(s):
Online pharmacy Valisure reported that it found a new carcinogenic impurity in some lots of blood pressure medicine valsartan, but the amount is still well below levels the FDA deemed potentially harmful.
The objective was to provide a minimally invasive neovaginoplasty technique to construct a nearly physiological vagina to facilitate sexual functioning and appropriate vaginal length in patients with congenital vaginal agenesis. This is a retrospective study at a tertiary care hospital. 52 patients with congenital vaginal agenesis owing to Mayer-Rokitansky-Küster-Hauser syndrome or androgen insensitivity syndrome presented for vaginal reconstruction. Modified McIndoe vaginoplasty was done in all patients between 2010 and 2018using a vaginal mold created with glove, nonadherent petroleum gauze, and Interceed absorbable...
Publication date: May 2019Source: Best Practice &Research Clinical Obstetrics &Gynaecology, Volume 57Author(s):