European journal of clinical investigation
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Eur. J. Clin. Invest. · Dec 2024
The hinge-1 domain of Flna is not necessary for diverse physiological functions in mice.
The filamins are cytoskeletal binding proteins that dynamically crosslink actin into orthogonal networks or bundle it into stress fibres. The domain structure of filamin proteins is very well characterised, with an N-terminal actin-binding region, followed by 24 immunoglobulin-like repeat units. The repeat domains are separated into distinct segments by two regions of low-complexity known as hinge-1 and hinge-2. The role of hinge-1 especially has been proposed to be essential for protein function as it provides flexibility to the otherwise rigid protein, and is a target for cleavage by calpain. Hinge-1 protects cells from otherwise destructive forces, and the products of calpain cleavage are involved in critical cellular signalling processes, such as survival during hypoxia. Pathogenic variants in FLNA encoding Filamin A, including those that remove the hinge-1 domain, cause a wide range of survivable developmental disorders. In contrast, complete loss of function of this gene is embryonic lethal in human and mouse. ⋯ We conclude that hinge-1 is dispensable for filamin A protein function during development over the murine lifespan.
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Eur. J. Clin. Invest. · Dec 2024
Respiratory dysfunction in old mice could be related to inflammation and lung fibrosis induced by hyperphosphatemia.
With age, lungs undergo typical changes that lead to a deterioration of respiratory function. Our aim was to assess the role of age-associated hyperphosphatemia in these changes. ⋯ These results suggest that age-related hyperphosphatemia induces inflammation, fibrosis, and impaired respiratory function in old mice; these effects appear to be mediated by ET-1 and NFkB activation.
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Eur. J. Clin. Invest. · Dec 2024
Review Meta AnalysisThe prognostic value of mean platelet volume in patients with coronary artery disease: An updated systematic review with meta-analyses.
Mean platelet volume (MPV) is a widely available laboratory index, however its prognostic significance in patients with coronary artery disease (CAD) is still unclear. We intended to investigate and pool the evidence on the prognostic utility of admission MPV in predicting clinical outcomes in patients with CAD. ⋯ The meta-analysis found robust evidence on the link between admission MPV and the increased risk of long-term mortality in patients with CAD patients, as well as in patients who underwent PCI and patients presented with ACS.
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Eur. J. Clin. Invest. · Dec 2024
Review Meta AnalysisGlucagon-like peptide-1 receptor agonist semaglutide reduces atrial fibrillation incidence: A systematic review and meta-analysis.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are new anti-hyperglycaemic drugs with proven cardiovascular (CV) benefit in diabetic and non-diabetic patients at high CV risk. Despite a neutral class effect on arrhythmia risk, data on semaglutide suggest a possible drug-specific benefit in reducing atrial fibrillation (AF) occurrence. ⋯ Semaglutide significantly reduces the occurrence of incident AF by 42% as compared to placebo in individuals at high CV risk, mainly affected by type 2 diabetes mellitus. This effect appears to be consistent independently of the route of administration of the drug (oral or subcutaneous), the presence of underlying diabetes and BMI.
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Eur. J. Clin. Invest. · Dec 2024
ReviewWhen less is more: The association between the expression of polymorphic CYPs and AFB1-induced HCC.
An individual's genetic fingerprint is emerging as a pivotal predictor of numerous disease- and treatment-related factors. Single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes play key roles in an individual's exposure to a malignancy-associated risk, such as Aflatoxin B1 (AFB1)-induced hepatocellular carcinoma (HCC). ⋯ Polymorphic variants of CYP enzymes have a functional impact on the susceptibility to AFB1-induced HCC. Outlining such variation and their implications may provide deeper insights into approaching HCC in a more personalized manner for guiding future risk-assessment, diagnosis, and treatment.