Salt-Intake-Related Behavior Varies between Sexes and Is Strongly Associated with Daily Salt Consumption in Obese Patients at High Risk for MASLD.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) imposes a significant burden on Westernized regions. The Western diet, high in salt intake, significantly contributes to disease development. However, there are a lack of data on salt literacy and salt intake among MASLD patients in Germany. Our study aims to analyze daily salt intake and salt-intake-related behavior in MASLD patients. METHODS: 234 MASLD patients were prospectively included. Daily salt intake and salt-intake-related behavior were assessed via a food frequency questionnaire (FFQ-DEGS) and a salt questionnaire (SINU). Statistical analyses were performed using SPSS. RESULTS: Mean daily salt intake was higher in men than in women (7.3 ± 5 g/d vs. 5.3 ± 4 g/d; p < 0.001). There was significant agreement between increased daily salt intake (>6 g/d) and the behavioral salt index (SI) (p < 0.001). Men exhibited higher SI scores compared to women, indicating lower awareness of salt in everyday life. Multivariate analysis identified specific salt-intake-related behaviors impacting daily salt consumption. CONCLUSIONS: Our study reveals a strong link between daily salt intake and salt-intake-related behavior, highlighting sex-specific differences in an MASLD cohort. To enhance patient care in high-cardiovascular-risk populations, specific behavioral approaches may be considered, including salt awareness, to improve adherence to lifestyle changes, particularly in male patients.

Identifying drug targets in tissues and whole blood with thermal-shift profiling.

Monitoring drug-target interactions with methods such as the cellular thermal-shift assay (CETSA) is well established for simple cell systems but remains challenging in vivo. Here we introduce tissue thermal proteome profiling (tissue-TPP), which measures binding of small-molecule drugs to proteins in tissue samples from drug-treated animals by detecting changes in protein thermal stability using quantitative mass spectrometry. We report organ-specific, proteome-wide thermal stability maps and derive target profiles of the non-covalent histone deacetylase inhibitor panobinostat in rat liver, lung, kidney and spleen and of the B-Raf inhibitor vemurafenib in mouse testis. In addition, we devised blood-CETSA and blood-TPP and applied it to measure target and off-target engagement of panobinostat and the BET family inhibitor JQ1 directly in whole blood. Blood-TPP analysis of panobinostat confirmed its binding to known targets and also revealed thermal stabilization of the zinc-finger transcription factor ZNF512. These methods will help to elucidate the mechanisms of drug action in vivo.

TRAIL-R1 and TRAIL-R2 Mediate TRAIL-Dependent Apoptosis in Activated Primary Human B Lymphocytes.

The maintenance of B cell homeostasis requires a tight control of B cell generation, survival, activation, and maturation. In lymphocytes upon activation, increased sensitivity to apoptotic signals helps controlling differentiation and proliferation. The death receptor Fas is important in this context because genetic Fas mutations in humans lead to an autoimmune lymphoproliferative syndrome that is similar to lymphoproliferation observed in Fas-deficient mice. In contrast, the physiological role of TNF-related apoptosis-inducing ligand receptors (TRAIL-Rs) in humans has been poorly studied so far. Indeed, most studies have focused on tumor cell lines and on mouse models whose results are difficult to transpose to primary human B cells. In the present work, the expression of apoptosis-inducing TRAIL-R1 and TRAIL-R2 and of the decoy receptors TRAIL-R3 and TRAIL-R4 was systematically studied in all developmental stages of peripheral B cells isolated from the blood and secondary lymphoid organs. Expression of TRAIL-Rs is modulated along development, with highest levels observed in germinal center B cells. In addition, T-dependent and T-independent signals elicited induction of TRAIL-Rs with distinct kinetics, which differed among B cell subpopulations: switched memory cells rapidly upregulated TRAIL-R1 and -2 upon activation while naïve B cells only reached similar expression levels at later time points in culture. Increased expression of TRAIL-R1 and -2 coincided with a caspase-3-dependent sensitivity to TRAIL-induced apoptosis in activated B cells but not in freshly isolated resting B cells. Finally, both TRAIL-R1 and TRAIL-R2 could signal actively and both contributed to TRAIL-induced apoptosis. In conclusion, this study provides a systematic analysis of the expression of TRAIL-Rs in human primary B cells and of their capacity to signal and induce apoptosis. This dataset forms a basis to further study and understand the dysregulation of TRAIL-Rs and TRAIL expression observed in autoimmune diseases. Additionally, it will be important to foresee potential bystander immunomodulation when TRAIL-R agonists are used in cancer treatment.