A potential age-independent MASLD-related liver fibrosis index based on metabolic profiling.

The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is of immediate concern, as its prevalence is increasing worldwide. MASLD often progresses to liver fibrosis, posing significant health risks. Age-independent, noninvasive tools to evaluate fibrosis are needed to improve diagnostic accuracy across all age groups.

Distinct Platelet Phenotype and Reactivity in Individuals with Permanent Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Pilot Study.

Atrial fibrillation (AF) is linked to an elevated risk of thromboembolic events. Despite the use of guideline-recommended direct anticoagulants (DOACs), a significant proportion of AF patients show a residual risk of thromboembolic events, driven by mechanisms that are not fully understood.We conducted a pilot study to characterize the platelet function in DOACs-treated AF patients, to explore whether an association between platelets and the residual thromboembolic risk exists.

A SPLICS reporter reveals [Formula: see text]-synuclein regulation of lysosome-mitochondria contacts which affects TFEB nuclear translocation.

Mitochondrial and lysosomal activities are crucial to maintain cellular homeostasis: optimal coordination is achieved at their membrane contact sites where distinct protein machineries regulate organelle network dynamics, ions and metabolites exchange. Here we describe a genetically encoded SPLICS reporter for short- and long- juxtapositions between mitochondria and lysosomes. We report the existence of narrow and wide lysosome-mitochondria contacts differently modulated by mitophagy, autophagy and genetic manipulation of tethering factors.

Breakthrough infections after COVID-19 vaccinations do not elicit platelet hyperactivation and are associated with high platelet-lymphocyte and low platelet-neutrophil aggregates.

Background: Severe COVID-19 is associated with an excessive immunothrombotic response and thromboinflammatory complications. Vaccinations effectively reduce the risk of severe clinical outcomes in patients with COVID-19, but their impact on platelet activation and immunothrombosis during breakthrough infections is not known.

Objectives: To investigate how preemptive vaccinations modify the platelet-immune crosstalk during COVID-19 infections.

Distinct platelet crosstalk with adaptive and innate immune cells after adenoviral and mRNA vaccination against SARS-CoV-2.

Background: Genetic-based COVID-19 vaccines have proved to be highly effective in reducing the risk of hospitalization and death. Because they were first distributed in a large-scale population, the adenoviral-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome, and the interplay between platelets and vaccinations increasingly gained attention.

Objectives: The objective of this article was to study the crosstalk between platelets and the vaccine-induced immune response.

Opposite Effects of mRNA-Based and Adenovirus-Vectored SARS-CoV-2 Vaccines on Regulatory T Cells: A Pilot Study.

New-generation mRNA and adenovirus vectored vaccines against SARS-CoV-2 spike protein are endowed with immunogenic, inflammatory and immunomodulatory properties. Recently, BioNTech developed a noninflammatory tolerogenic mRNA vaccine (MOGm1Ψ) that induces in mice robust expansion of antigen-specific regulatory T (Treg) cells. The Pfizer/BioNTech BNT162b2 mRNA vaccine against SARS-CoV-2 is identical to MOGm1Ψ except for the lipid carrier, which differs for containing lipid nanoparticles rather than lipoplex.

Platelet and immune signature associated with a rapid response to the BNT162b2 mRNA COVID-19 vaccine.

Background: A rapid immune response is critical to ensure effective protection against COVID-19. Platelets are first-line sentinels of the vascular system able to rapidly alert and stimulate the immune system. However, their role in the immune response to vaccines is not known.

Expanded [CCTG]n repetitions are not associated with abnormal methylation at the CNBP locus in myotonic dystrophy type 2 (DM2) patients.

Myotonic Dystrophy type 2 (DM2) is a multisystemic disorder associated with an expanded [CCTG]n repeat in intron 1 of the CNBP gene. Epigenetic modifications have been reported in many repeat expansion disorders, including myotonic dystrophy type 1 (DM1), either as a mechanism to explain somatic repeat instability or transcriptional alterations in disease genes. The purpose of our work was to determine the effect of DM2 mutation on the methylation status of CpG islands localized in the 5' promoter region and in the 3' end of the [CCTG]n expansion of the CNBP gene.