The cIAP ubiquitin ligases sustain type 3 γδ T cells and ILC during aging to promote barrier immunity.

Early-life cues shape the immune system during adulthood. However, early-life signaling pathways and their temporal functions are not well understood. Herein, we demonstrate that the cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2), which are E3 ubiquitin ligases, sustain interleukin (IL)-17-producing γ δ T cells (γδT17) and group 3 innate lymphoid cells (ILC3) during late neonatal and prepubescent life.

Oxidative Stress and Indicators of Brain Damage Following Pediatric Heart Surgery.

Pediatric cardiac surgery induces an increased oxidative stress (OS) response. Increased OS is associated with poor neurologic outcomes in neonatal populations with similar patterns of brain injury. We investigated OS and brain injury in infants undergoing heart surgery.

Ozone therapy for patients with COVID-19 pneumonia: Preliminary report of a prospective case-control study.

Background: There is still no specific treatment strategies for COVID-19 other than supportive management.

Design: A prospective case-control study determined by admittance to the hospital based on bed availability.

Participants: Eighteen patients with COVID-19 infection (laboratory confirmed) severe pneumonia admitted to hospital between 20th March and 19th April 2020.

Potential Role of Oxygen-Ozone Therapy in Treatment of COVID-19 Pneumonia.

BACKGROUND Pneumonia caused by coronavirus originated in Wuhan, China in late 2019 and has spread around the world, becoming a pandemic. Many patients deteriorate rapidly and require intubation and mechanical ventilation, which is causing the collapse of healthcare systems in many countries. Coronavirus infection is associated with extensive lung inflammation and microvascular thrombosis, which can result in hypoxia.

The neonatal microenvironment programs innate γδ T cells through the transcription factor STAT5.

IL-17-producing RORγt+ γδ T cells (γδT17 cells) are innate lymphocytes that participate in type 3 immune responses during infection and inflammation. Herein, we show that γδT17 cells rapidly proliferate within neonatal lymph nodes and gut, where, upon entry, they upregulate T-bet and coexpress IL-17, IL-22, and IFN-γ in a STAT3- and retinoic acid-dependent manner. Neonatal expansion was halted in mice conditionally deficient in STAT5, and its loss resulted in γδT17 cell depletion from all adult organs.

The immune checkpoint receptor associated phosphatases SHP-1 and SHP-2 are not required for γδT17 cell development, activation, or skin inflammation.

IL-17-producing gamma delta (γδT17) cells are innate lymphocytes critical for antibacterial protection at barrier surfaces such as the skin but also highly pathogenic during inflammation. It is therefore important to understand the cellular and molecular mechanisms that could counter-balance overt γδT17 cell activation. Immune checkpoint receptors (ICRs) deliver inhibitory signals to activated lymphocytes and have been implicated as negative regulators of mouse γδT17 cells.

STAT3 but not STAT4 is critical for γδT17 cell responses and skin inflammation.

The transcription factors STAT3 and STAT4 are essential for lymphocyte differentiation and function. Interleukin (IL)-17 producing γδ T (γδT17) cells are innate lymphocytes important for anti-bacterial and inflammatory responses at barrier surfaces. Herein, we examine the role of STAT3 and STAT4 in regulating the homeostasis, activation, and pathogenicity of γδT17 cells.

Neuromyelitis optica spectrum disorders: Comparison according to the phenotype and serostatus.

Objective: To (1) determine the value of the recently proposed criteria of neuromyelitis optica (NMO) spectrum disorder (NMOSD) that unify patients with NMO and those with limited forms (NMO/LF) with aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies; and (2) investigate the clinical significance of the serologic status in patients with NMO.

Methods: This was a retrospective, multicenter study of 181 patients fulfilling the 2006 NMO criteria (n = 127) or NMO/LF criteria with AQP4-IgG (n = 54). AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies were tested using cell-based assays.

Pharmacological characterization of abediterol, a novel inhaled β(2)-adrenoceptor agonist with long duration of action and a favorable safety profile in preclinical models.

Abediterol is a novel potent, long-acting inhaled β(2)-adrenoceptor agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. Abediterol shows subnanomolar affinity for the human β(2)-adrenoceptor and a functional selectivity over β(1)-adrenoceptors higher than that of formoterol and indacaterol in both a cellular model with overexpressed human receptors and isolated guinea pig tissue. Abediterol is a full agonist at the human β(2)-adrenoceptor (E(max) = 91 ± 5% of the maximal effect of isoprenaline).

Analysis of relapses in anti-NMDAR encephalitis.

Objective: The clinical characteristics of patients with relapsing anti-NMDA receptor (NMDAR) encephalitis are not well-defined. In this study, we report the clinical profile and outcome of relapses in a series of anti-NMDAR encephalitis.

Methods: We did a retrospective review of relapses that occurred in 25 patients with anti-NMDAR encephalitis.

Characterization of aclidinium bromide, a novel inhaled muscarinic antagonist, with long duration of action and a favorable pharmacological profile.

Aclidinium bromide is a novel potent, long-acting inhaled muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease. Aclidinium showed subnanomolar affinity for the five human muscarinic receptors (M(1)-M(5)). [(3)H]Aclidinium dissociated slightly faster from M(2) and M(3) receptors than [(3)H]tiotropium but much more slowly than [(3)H]ipratropium.

Drosophila host defense after oral infection by an entomopathogenic Pseudomonas species.

Drosophila has been shown to be a valuable model for the investigation of host-pathogen interactions. Study of the Drosophila immune response has been hampered, however, by the lack of true Drosophila pathogens. In nearly all studies reported, the bacteria used were directly injected within the body cavity of the insect, bypassing the initial steps of a natural interaction.

Aspirin increases CD36, SR-BI, and ABCA1 expression in human THP-1 macrophages.

Objective: CD36 is a receptor, whose expression increases during the differentiation of monocytes to macrophages, playing a key role in the phagocytosis of apoptotic cells and in the formation of foam cells during atherosclerosis. Recently, it has been described that ligands of PPARgamma induce CD36 expression and inhibit cyclooxygenase expression in macrophages. Our aim was to study whether the reduction of endogenous prostaglandin production could modify CD36 expression in macrophages and to outline the potential mechanism.

Reduction of intracellular cholesterol accumulation in THP-1 macrophages by a combination of rosiglitazone and atorvastatin.

Rosiglitazone and atorvastatin combination therapy has beneficial effects on both glycemic control and plasma lipid levels in type 2 diabetic patients. In the present study, we sought to determine whether this combination can also exert direct antiatherosclerotic effects in macrophages. Our results show that 2 microM rosiglitazone, alone or combined with 5 microM atorvastatin, significantly upregulated the expression of the ATP-binding cassette transporter ABCA1 and of the class B scavenger receptor CLA-1 (CD36 and LIMPII analog), both involved in cholesterol efflux from macrophages.

[Prevalence of patent foramen ovale in young patients with cerebral ischemic accident of unknown origin].

Introduction And Objective: Patent foramen ovale has been associated with stroke in young patients with cryptogenic stroke. The purpose of this study is to examine the prevalence of patent foramen ovale in this group of patients, as well as their anatomical and functional characteristics by contrast echocardiography, trying to determine ictus risk markers in young patients with acute ischemic stroke.

Patients And Method: Prospective study of 90 patients under the age of 50 who were hospitalised consecutively due to a clinical presentation suggestive of stroke.

Role of SR-BI in regulating lipoprotein structure and metabolism.

The scavenger receptor class B type I (SR-BI) is a cell surface lipoprotein receptor that mediates physiologically relevant selective cholesteryl ester uptake from high-density lipoprotein (HDL). SR-BI appears to be required for the maintenance of reverse cholesterol transport, normal HDL levels and HDL structure by means of hepatic-selective HDL-cholesterol and phospholipid uptake in mice. SR-BI can also promote the selective uptake of cholesteryl ester from apoB-containing lipoproteins; however, unlike the effect of SR-BI on HDL-cholesterol, the effect on low-density lipoprotein is limited in vivo.

Identification of the N-linked glycosylation sites on the high density lipoprotein (HDL) receptor SR-BI and assessment of their effects on HDL binding and selective lipid uptake.

The murine class B, type I scavenger receptor mSR-BI, a high density lipoprotein (HDL) receptor that mediates selective uptake of HDL lipids, contains 11 potential N-linked glycosylation sites and unknown numbers of both endoglycosidase H-sensitive and -resistant oligosaccharides. We have examined the consequences of mutating each of these sites (Asn --> Gln or Thr --> Ala) on post-translational processing of mSR-BI, cell surface expression, and HDL binding and lipid transport activities. All 11 sites were glycosylated; however, disruption of only two (Asn-108 and Asn-173) substantially altered expression and function.

Regulatory effects of HDL on smooth muscle cell prostacyclin release.

One mechanism by which high density lipoproteins (HDLs) exert their protective effect against coronary artery disease could be related to the induction of prostacyclin (PGI(2)) release in the vessel wall. We have recently shown that HDL increases PGI(2) production in rabbit smooth muscle cells (RSMCs) and that this increase is dependent on cyclooxygenase-2 (Cox-2). Here we analyze the mechanism by which rabbit HDL induces PGI(2) release in RSMCs.

Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology.

The high density lipoprotein (HDL) receptor SR-BI (scavenger receptor class B type I) mediates the selective uptake of plasma HDL cholesterol by the liver and steroidogenic tissues. As a consequence, SR-BI can influence plasma HDL cholesterol levels, HDL structure, biliary cholesterol concentrations, and the uptake, storage, and utilization of cholesterol by steroid hormone-producing cells. Here we used homozygous null SR-BI knockout mice to show that SR-BI is required for maintaining normal biliary cholesterol levels, oocyte development, and female fertility.

HDL-induced prostacyclin release in smooth muscle cells is dependent on cyclooxygenase-2 (Cox-2).

Cyclooxygenase-1 (Cox-1) and Cox-2 are key enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. We studied the effects of plasma HDL and LDL on the synthesis of prostacyclin, Cox-1/Cox-2 mRNA, and protein expression by rabbit aortic smooth muscle cells. Prostacyclin synthesis was measured by enzyme immunoassay (EIA) of the stable metabolite of prostacyclin (PGI2), 6-ketoprostaglandin F1 alpha.

Mevalonate deprivation impairs IGF-I/insulin signaling in human vascular smooth muscle cells.

3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitors (statins) are therapeutically used to lower plasma cholesterol levels. In addition, these drugs can block vascular smooth muscle cell (VSMC) proliferation. The present study addressed the question whether the inhibitory effect of lovastatin on premitotic DNA synthesis correlates with a downregulation of c-fos mRNA levels, a marker of signaling efficiency, in human SMC.

[Antiemetic prophylaxis after laparoscopic cholecystectomy: comparative study of dehydrobenzperidol, metoclopramide, ondansetron and placebo].

Objectives: To compare the efficacy of ondansetron to that of metoclopramide, dehydrobenzperidol and placebo for the prevention of postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy in a double-blind random study.

Patients And Method: A total of 100 ASA I, II and III patients undergoing scheduled laparoscopic cholecystectomy were divided into 4 groups according to whether they received one of the following intravenously just prior to anesthetic induction: 1.25 mg dehydrobenzperidol (group D), 10 mg metoclopramide (group M), 4 mg ondansetron (group O) or 2 ml of saline (group P).

[Posterior cortical dementia].

Two patients, aged 59 and 73 years, presented with the clinical syndrome of Posterior Cortical Dementia (PCD). Follow-up during 3 and 11 years confirmed the progressive nature of the disorder. Posterior cerebral impairment was seen on SPECT studies.

Fibrates modify rat hepatic fatty acid chain elongation and desaturation in vitro.

Three fibric acid derivatives, clofibric acid (CFB), bezafibrate (BFB), and gemfibrozil (GFB), mainly used in the treatment of hypertriglyceridaemic or mixed hyperlipidaemic states, have been tested for their ability to modify fatty acid chain elongation and desaturation in vitro. Both endogenous and exogenous (saturated, monounsaturated and polyunsaturated) fatty acid elongations were inhibited by fibrates at concentrations well within the physiological range (IC50 values for GFB were between 0.1 and 0.

Cytosolic lipogenic enzymes: effect of fibric acid derivatives in vitro.

The effect of fibric acid derivatives, clofibric acid (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on hepatic cytosolic enzymatic activities involved in saturated fatty acid synthesis has been estudied in vitro. From all the activities tested (fatty acid synthetase, acetyl-CoA carboxylase, ATP-citrate lyase, malic enzyme, malic dehydrogenase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase), only acetyl-CoA carboxylase and glucose-6-phosphate dehydrogenase were significantly inhibited by fibrates, with the following order of potency: GFB > BFB > > CFB. The characteristics of the inhibition phenomena (IC50, kinetic analysis, time and protein dependence, etc) and their transcendence to the effects of fibric acid derivatives in vivo are discussed.