Downregulation of type I interferon signalling pathway by urate in primary human PBMCs.

Type I interferons (IFN1s) mediate innate responses to microbial stimuli and regulate interleukin (IL)-1 and IL-1 receptor antagonist (Ra) production in human cells. This study explores interferon-stimulated gene (ISG) alterations in the transcriptome of patients with gout and stimulated human primary cells in vitro in relation to serum urate concentrations. Peripheral blood mononuclear cells (PBMCs) and monocytes of patients with gout were primed in vitro with soluble urate, followed by lipopolysaccharide (LPS) stimulation.

Long-Lasting Enhanced Cytokine Responses Following SARS-CoV-2 BNT162b2 mRNA Vaccination.

The mRNA vaccine against COVID-19 protects against severe disease by the induction of robust humoral and cellular responses. Recent studies have shown the capacity of some vaccines to induce enduring non-specific innate immune responses by the induction of trained immunity, augmenting protection against unrelated pathogens. This study aimed to assess whether the mRNA vaccine BNT162b2 can induce lasting non-specific immune responses in myeloid cells following a three-dose vaccination scheme.

GWAS-identified hyperuricemia-associated IGF1R variant rs6598541 has a limited role in urate mediated inflammation in human mononuclear cells.

Gout is a common autoinflammatory joint diseases characterized by deposition of monosodium urate (MSU) crystals which trigger an innate immune response mediated by inflammatory cytokines. IGF1R is one of the loci associated with both urate levels and gout susceptibility in GWAS to date, and IGF-1-IGF-1R signaling is implicated in urate control. We investigate the role of IGF-1/IGF1R signaling in the context of gouty inflammation.

Regulation of SOCS3-STAT3 in urate-induced cytokine production in human myeloid cells.

Objective: Hyperuricaemia is necessary for gout. High urate concentrations have been linked to inflammation in mononuclear cells. Here, we explore the role of the suppressor of cytokine signaling 3 (SOCS3) in urate-induced inflammation.

Increased Levels of VCAM-1 in Patients with High Cardiovascular Risk and Obstructive Sleep Apnea Syndrome.

(1) Background: Although obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity, the link between OSA and cardiovascular disease (CVD) is not completely elucidated. Thus, we aim to assess cardiovascular risk (CVR) using SCORE 2 and SCORE 2 for older persons (SCORE 2OP), and to evaluate the association between the endothelial biomarkers VCAM-1, ICAM-1, epicardial fat, and sleep study parameters in order to improve current clinical practices and better understand the short-and long-term CVRs in OSA patients. (2) Methods: 80 OSA patients and 37 healthy volunteers were enrolled in the study.

Hyperuricemia remodels the serum proteome toward a higher inflammatory state.

Gout is an autoinflammatory disease triggered by a complex innate immune response to MSU crystals and inflammatory triggers. While hyperuricemia is an obligatory risk factor for the development of gout, the majority of individuals with hyperuricemia never develop gout but have an increased risk of developing cardiometabolic disorders. Current management of gout aims at MSU crystal dissolution by lowering serum urate.

TGF-β is elevated in hyperuricemic individuals and mediates urate-induced hyperinflammatory phenotype in human mononuclear cells.

Background: Soluble urate leads to a pro-inflammatory phenotype in human monocytes characterized by increased production of IL-1β and downregulation of IL-1 receptor antagonist, the mechanism of which remains to be fully elucidated. Previous transcriptomic data identified differential expression of genes in the transforming growth factor (TGF)-β pathway in monocytes exposed to urate in vitro. In this study, we explore the role of TGF-β in urate-induced hyperinflammation in peripheral blood mononuclear cells (PBMCs).

The role of 3D speckle tracking echocardiography in the diagnosis of obstructive sleep apnea and its severity.

There is a consistent relationship between obstructive sleep apnea (OSA) and cardiovascular diseases. It is already recognized that OSA may influence the geometry and function of the right ventricle (RV). This has encouraged the development of echocardiographic evaluation for screening of OSA and its severity.

A Prospective Study of CPAP Therapy in Relation to Cardiovascular Outcome in a Cohort of Romanian Obstructive Sleep Apnea Patients.

Background: Despite efforts at treatment, obstructive sleep apnea (OSA) remains a major health problem, especially with increasing evidence showing an association with cardiovascular morbidity and mortality. The treatment of choice for OSA patients is Continuous Positive Airway Pressure (CPAP), which has been proven in randomized controlled trials to be an effective therapy for this condition. The impact of CPAP on the cardiovascular pathology associated with OSA remains, however, unclear.

Urate-induced immune programming: Consequences for gouty arthritis and hyperuricemia.

Trained immunity is a process in which innate immune cells undergo functional reprogramming in response to pathogens or damage-associated molecules leading to an enhanced non-specific immune response to subsequent stimulation. While this capacity to respond more strongly to stimuli is beneficial for host defense, in some circumstances it can lead to maladaptive programming and chronic inflammation. Gout is characterized by persistent low-grade inflammation and is associated with an increased number of comorbidities.