Chemokines and eicosanoids fuel the hyperinflammation within the lungs of patients with severe COVID-19.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to a variety of clinical outcomes, ranging from the absence of symptoms to severe acute respiratory disease and ultimately death. A feature of patients with severe coronavirus disease 2019 (COVID-19) is the abundance of inflammatory cytokines in the blood. Elevated levels of cytokines are predictive of infection severity and clinical outcome.

High levels of eicosanoids and docosanoids in the lungs of intubated COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 is responsible for coronavirus disease 2019 (COVID-19). While COVID-19 is often benign, a subset of patients develops severe multilobar pneumonia that can progress to an acute respiratory distress syndrome. There is no cure for severe COVID-19 and few treatments significantly improved clinical outcome.

Arthroscopic Latarjet procedure: is optimal positioning of the bone block and screws possible? A prospective computed tomography scan analysis.

Hypothesis: We hypothesized that the arthroscopic Latarjet procedure could be performed with accurate bone block positioning and screw fixation with a similar rate of complications to the open Latarjet procedure.

Methods: In this prospective study, 105 shoulders (104 patients) underwent the arthroscopic Latarjet procedure performed by the same senior surgeon. The day after surgery, an independent surgeon examiner performed a multiplanar bidimensional computed tomography scan analysis.

A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy.

Vps34 is a phosphoinositide 3-kinase (PI3K) class III isoform that has attracted major attention over the recent years because of its role in autophagy. Herein we describe the biological characterization of SAR405, which is a low-molecular-mass kinase inhibitor of Vps34 (KD 1.5 nM).

A convertible shoulder system: is it useful in total shoulder arthroplasty revisions?

Purpose: The frequency of total shoulder arthroplasty (TSA) implantation is constantly increasing. This leads to revisions because of stem or glenoid component loosening, infection, instability or glenoid subsidence. Significant rotator cuff lesions and/or bone loss necessitate reverse shoulder arthroplasty (RSA) with bone reconstruction, which is a demanding procedure.

Identifying Small Molecules which Inhibit Autophagy: a Phenotypic Screen Using Image-Based High-Content Cell Analysis.

Autophagy plays an important role in cancer and it has been suggested that it functions not only as a tumor suppressor pathway to prevent tumor initiation, but also as a pro-survival pathway that helps tumor cells endure metabolic stress and resist death triggered by chemotherapeutic agents, including acquired resistance. We aimed to identify small-molecule autophagy inhibitors using a HTS/HCA approach through a phenotypic, cell image-based assay, in order to screen multiple biological targets simultaneously and to screen compounds in a physiologically relevant environment. LC3 is a component of the autophagosome, which undergoes a cytoplasmic redistribution from diffuse to punctate dots during autophagy.

Purification and characterization of human DNA topoisomerase IIIalpha.

Human topoisomerase IIIalpha (hTopo IIIalpha), the recently identified first member of the topoisomerase IA subfamily in humans, has a central domain which is highly homologous to the yeast topoisomerase III, but an overall organization closer to that of Escherichia coli DNA topoisomerase I. In order to determine the properties of hTopo IIIalpha, compared to those of other topoisomerase IA subfamily members, we purified this enzyme to near homogeneity, together with an active site-mutant Y337F. We show that hTopo IIIalpha is able to relax negatively supercoiled DNA in a distributive manner, leading to the total disappearance of the initial substrate and the appearance of intermediate topoisomers.

Differential ability of tachykinin NK-1 and NK-2 agonists to produce scratching and grooming behaviours in mice.

Potent and selective NK-1 and NK-2 agonists as well as compounds with lower selectivity and affinity for NK-1 binding sites were compared in their ability to produce scratching and grooming behaviours when injected intracerebroventricularly in mice. Septide, an agonist with a low affinity for NK-1 binding sites, [Sar9, Met(O2)11]SP and to a lesser extent [Pro9]SP, two potent and selective NK-1 agonists were the most effective drugs in stimulating these behaviours. Only high doses of [Apa9,10]SP and [Lys5, Tyr7, Pro8]NKA(4-10), two agonists with low affinity for NK-1 binding sites, produced scratching and grooming responses.

Characterization of a human NK1 tachykinin receptor in the astrocytoma cell line U 373 MG.

The human NK1 tachykinin receptor in the astrocytoma cell line U 373 MG was characterized using selective agonists and antagonists described for this receptor in the rat. Specific [3H]substance P binding sites were present on cell homogenates, whereas [3H]neurokinin A or [3H]-senktide binding sites were absent. The binding was saturable and reversible.