European journal of clinical investigation
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Eur. J. Clin. Invest. · Mar 2024
Targeting the SPHK1/S1P/S1PR2 axis ameliorates GH-secreted pituitary adenoma progression.
Growth hormone-secreted pituitary adenoma (GHPA) is a prominent subtype of pituitary adenoma (PA) associated with progressive somatic disfigurement, various complications, and elevated mortality rates. Existing treatment options have limited efficacy, highlighting the urgent need for novel pharmacological interventions. Previous studies have revealed that sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptors (S1PRs) signalling have critical roles in the tumour microenvironment, but their role in GHPA remains unclear. ⋯ Our study shows that blocking SPHK1/S1P/S1PR2 axis can ameliorate the progression of GHPA, providing evidence of a promising therapeutic target for GHPA.
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Eur. J. Clin. Invest. · Mar 2024
Observational StudyEffectiveness of a fourth SARS-CoV-2 vaccine dose in previously infected individuals from Austria.
Evidence is limited on the effectiveness of a fourth vaccine dose against coronavirus disease 2019 (COVID-19) in populations with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We estimated the risk of COVID-19 deaths and SARS-CoV-2 infections according to vaccination status in previously infected individuals in Austria. ⋯ In previously infected individuals, a fourth vaccination was not associated with COVID-19 death risk, but with transiently reduced risk of SARS-CoV-2 infections and reversal of this effect in longer follow-up. All-cause mortality data suggest healthy vaccinee bias.
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Eur. J. Clin. Invest. · Mar 2024
ReviewRecent advances in mechanistic studies of heart failure with preserved ejection fraction and its comorbidities-Role of microRNAs.
Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome with a complex aetiology commonly associated with comorbidities such as diabetes mellitus, obesity, hypertension and renal disease. Various diseases induce systemic, chronic and low-grade inflammation; microvascular dysfunction; metabolic stress; tissue ischemia; and fibrosis, leading to HFpEF. An effective treatment for HFpEF is lacking, largely owing to its pathophysiological heterogeneity. Recent studies have revealed that microRNAs (miRNAs) play crucial roles in regulating the pathogenesis of HFpEF and its comorbidities. ⋯ A customized strategy based on miRNAs has emerged as an effective treatment for HFpEF. In this review, we discuss recent research surrounding miRNAs and HFpEF and propose potential miRNA targets for the pathophysiology of HFpEF and its comorbidities. Although current research concerning miRNAs and their therapeutic potential is in its early stages, miRNA-based diagnostics and therapeutics hold great promise in the future.
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Eur. J. Clin. Invest. · Mar 2024
CDK5R1, GSE1, HSPG2 and WDFY3 as indirect epigenetic-sensitive genes in atrial fibrillation.
Although mounting evidence supports that aberrant DNA methylation occurs in the hearts of patients with atrial fibrillation (AF), noninvasive epigenetic characterization of AF has not yet been defined. ⋯ CDK5R1, GSE1, HSPG2 and WDFY3 resulted the best discriminatory genes both at methylation and gene expression level. Our results provide several candidate diagnostic biomarkers with the potential to advance precision medicine in AF.
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Eur. J. Clin. Invest. · Mar 2024
Lipidomics of triglyceride-rich lipoproteins derived from hyperlipidemic patients on inflammation.
Triglyceride-rich lipoproteins (TRLs) can have an important role in atherosclerosis development due to their size and ability to penetrate the endothelium. While high plasma triglyceride (TG) levels and chronic inflammation are relevant in metabolic diseases, it remains unclear whether TGs are atherogenic or which TRL-TG-derived metabolites are responsible for inflammation. Here, we aimed to study the lipidome modifications of TRL particles enriched in TG in patients with hyperlipidemia and their associations with a proinflammatory status both in vivo and in vitro. ⋯ High TRL-TG levels are associated with a higher systemic inflammatory status and increased particle concentrations. In vitro, higher particle numbers increase proinflammatory cytokine secretion, with cholesterol and phospholipid-rich TRL being more proinflammatory.