Case Report: A rare transthyretin mutation p.D58Y in a Chinese case of transthyretin amyloid cardiomyopathy.

Hereditary transthyretin amyloid (ATTRv) cardiomyopathy (CM) is caused by mutations in the TTR gene. TTR mutations contribute to TTR tetramer destabilization and dissociation, leading to excessive deposition of insoluble amyloid fibrils in the myocardium and finally resulting in cardiac dysfunction. In this article, we report a case of a Chinese patient with transthyretin mutation p.D58Y and provide detailed information on cardiac amyloidosis, including transthoracic echocardiography, cardiac magnetic resonance, and SPECT imaging for the first time. Our report aims to provide a better understanding of ATTR genotypes and phenotypes.

Inhibition of HSP20 Ameliorates Steatotic Liver Disease by Stimulating ERK2-Dependent Autophagy.

HSP20 emerges as a novel regulator of autophagy in the heart. Nonetheless, the detailed function of HSP20 in the liver and its effect on autophagy remain unknown. Here, we observed that HSP20 expression is increased in liver tissues from mice and patients with metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease. Liver-specific downregulation of HSP20 mitigates hepatic steatosis and insulin resistance in obese mice, while upregulating HSP20 promotes lipid deposition and hepatocyte cell death. Mechanistically, liquid chromatography-tandem mass spectrometry revealed that HSP20 interacts with phosphorylated extracellular regulated protein kinase 2 (ERK2) and prevents its dephosphorylation by dual specificity phosphatase 6, leading to ERK2-mediated repression of autophagy and resulting in aggravated saturated fatty acid (SFA)-triggered hepatocyte death. Importantly, such adverse effects could be ameliorated by ERK inhibitor. Our data reveal a framework of how HSP20 increases susceptibility of SFA-induced liver injury through enhancing ERK2 phosphorylation, which represents a plausible therapeutic intervention to combat MASLD.

Myricanol attenuates sepsis-induced inflammatory responses by nuclear factor erythroid 2-related factor 2 signaling and nuclear factor kappa B/mitogen-activated protein kinase pathway via upregulating Sirtuin 1.

Sepsis, a life-threatening condition characterized by dysregulated immune responses, remains a significant clinical challenge. Myricanol, a natural compound, plays a variety of roles in regulating lipid metabolism, anti-cancer, anti-neurodegeneration, and it could act as an Sirtuin 1 (SIRT1) activator. This study aimed to explore the therapeutic potential and underlying mechanism of myricanol in the lipopolysaccharide (LPS)-induced sepsis model. In vivo studies revealed that myricanol administration significantly improved the survival rate of LPS-treated mice, effectively mitigating LPS-induced inflammatory responses in lung tissue. Furthermore, in vitro studies demonstrated that myricanol treatment inhibited the expression of pro-inflammatory cytokines, attenuated signal pathway activation, and reduced oxidative stress in macrophages. In addition, we demonstrated that myricanol selectively enhances SIRT1 activation in LPS-stimulated macrophages, and all of the protective effect of myricanol were reversed through SIRT1 silencing. Remarkably, the beneficial effects of myricanol against LPS-induced sepsis were abolished in SIRT1 myeloid-specific knockout mice, underpinning the critical role of SIRT1 in mediating myricanol's therapeutic efficacy. In summary, this study provides significant evidence that myricanol acts as a potent SIRT1 activator, targeting inflammatory signal pathways and oxidative stress to suppress excessive inflammatory responses. Our findings highlight the potential of myricanol as a novel therapeutic agent for the treatment of LPS-induced sepsis.