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Background Septic cardiomyopathy worsens the prognosis of critically ill patients. Clinical data suggest that interleukin‐1β (IL‐1β), activated by the NLRP3 inflammasome, compromises cardiac function. Whether or not deleting Nlrp3 would prevent cardiac atrophy and improve diastolic cardiac function in sepsis was unclear. Here, we investigated the role of NLRP3/IL‐1β in sepsis‐induced cardiomyopathy and cardiac atrophy. Methods Male Nlrp3 knockout (KO) and wild‐type (WT) mice were exposed to polymicrobial sepsis by caecal ligation and puncture (CLP) surgery (KO, n = 27; WT, n = 33) to induce septic cardiomyopathy. Sham‐treated mice served as controls (KO, n = 11; WT, n = 16). Heart weights and morphology, echocardiography and analyses of gene and protein expression were used to evaluate septic cardiomyopathy and cardiac atrophy. IL‐1β effects on primary and immortalized cardiomyocytes were investigated by morphological and molecular analyses. IonOptix and real‐time deformability cytometry (RT‐DC) analysis were used to investigate functional and mechanical effects of IL‐1β on cardiomyocytes. Results Heart morphology and echocardiography revealed preserved systolic (stroke volume: WT sham vs. WT CLP: 33.1 ± 7.2 μL vs. 24.6 ± 8.7 μL, P

The genetic placebo effect comprises the gene-related psychological, physiological and behavioral changes resulting from merely receiving genetic information. Although previous studies have found a genetic placebo effect resulting from fake genetic feedback, it is unclear whether the genetic placebo effect can occur independent of actual genetic dispositions and whether the genetic placebo effect varies across participants. Our research aimed to address this gap by testing the genetic placebo effect on psychological resilience when taking the impact of genes into consideration and investigating the moderating effect of self-compassion on the genetic placebo effect. Experiment 1 contained two groups of participants, a before-feedback group and an after-feedback group, whose psychological resilience was measured before (after) receiving genetic feedback about psychological resilience. We observed a weak genetic placebo effect independent of the impact of genes, indexed by the higher correlation between the genetic score and psychological resilience score in the after-feedback group. Moreover, self-compassion moderated the genetic placebo effect, and the participants with higher self-compassion were more sensitive to genetic feedback. These findings were replicated in experiment 2, in which we randomly gave genetic feedback to participants, reporting genetic predispositions of high or low psychological resilience. Our research enhanced the ecological validity of the genetic placebo effect and brought us insights into the use of genetic testing and feedback.

This paper provides a unique perspective for understanding cultural differences: representation similarity - a computational technique that uses pairwise comparisons of units to reveal their representation in higher-order space. By combining individual-level measures of trust across domains and well-being from 13,823 participants across 15 nations with a measure of society-level tightness-looseness, we found that any two countries with more similar tightness-looseness tendencies exhibit higher degrees of representation similarity in national interpersonal trust profiles. Although each individual’s trust profile is generally similar to their nation’s trust profile, the greater similarity between an individual’s and their society’s trust profile predicted a higher level of individual life satisfaction only in loose cultures, but not in tight cultures. Using the framework of representation similarity to explore cross-cultural differences from a multidimensional, multi-national perspective can provide a new and fuller understanding of culture and its influence on human well-being.

Cachexia is associated with poor prognosis in chronic heart failure patients, but the underlying mechanisms of cachexia triggered disease progression remain poorly understood. Here, we investigate whether the dysregulation of myokine expression from wasting skeletal muscle exaggerates heart failure. RNA sequencing from wasting skeletal muscles of mice with heart failure reveals a reduced expression of Ostn, which encodes the secreted myokine Musclin, previously implicated in the enhancement of natriuretic peptide signaling. By generating skeletal muscle specific Ostn knock-out and overexpressing mice, we demonstrate that reduced skeletal muscle Musclin levels exaggerate, while its overexpression in muscle attenuates cardiac dysfunction and myocardial fibrosis during pressure overload. Mechanistically, Musclin enhances the abundance of C-type natriuretic peptide (CNP), thereby promoting cardiomyocyte contractility through protein kinase A and inhibiting fibroblast activation through protein kinase G signaling. Because we also find reduced OSTN expression in skeletal muscle of heart failure patients, augmentation of Musclin might serve as therapeutic strategy., Cachexia is associated with poor prognosis in heart failure. Here the authors show that mice and patients with cardiac cachexia display reduced skeletal muscle expression and circulating levels of Musclin. Musclin ablation in skeletal muscle worsens, while its muscle-specific overexpression ameliorates heart failure in mice.

Background Critically ill patients develop atrophic muscle failure, which increases morbidity and mortality. Interleukin-1β (IL-1β) is activated early in sepsis. Whether IL-1β acts directly on muscle cells and whether its inhibition prevents atrophy is unknown. We aimed to investigate if IL-1β activation via the Nlrp3 inflammasome is involved in inflammation-induced atrophy. Methods We performed an experimental study and prospective animal trial. The effect of IL-1β on differentiated C2C12 muscle cells was investigated by analyzing gene-and-protein expression, and atrophy response. Polymicrobial sepsis was induced by cecum ligation and puncture surgery in Nlrp3 knockout and wild type mice. Skeletal muscle morphology, gene and protein expression, and atrophy markers were used to analyze the atrophy response. Immunostaining and reporter-gene assays showed that IL-1β signaling is contained and active in myocytes. Results Immunostaining and reporter gene assays showed that IL-1β signaling is contained and active in myocytes. IL-1β increased Il6 and atrogene gene expression resulting in myocyte atrophy. Nlrp3 knockout mice showed reduced IL-1β serum levels in sepsis. As determined by muscle morphology, organ weights, gene expression, and protein content, muscle atrophy was attenuated in septic Nlrp3 knockout mice, compared to septic wild-type mice 96 h after surgery. Conclusions IL-1β directly acts on myocytes to cause atrophy in sepsis. Inhibition of IL-1β activation by targeting Nlrp3 could be useful to prevent inflammation-induced muscle failure in critically ill patients. Electronic supplementary material The online version of this article (doi:10.1186/s40635-016-0115-0) contains supplementary material, which is available to authorized users.