Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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The monocyte to high-density lipoprotein-cholesterol (HDL-C) ratio (monocyte-to-HDL-C ratio) was proposed as a marker of atherosclerosis. Osteoporosis and atherosclerosis share common risk factors and pathophysiological mechanisms. This study aimed to assess the relationship between monocyte-to-HDL-C ratio and osteoporosis. ⋯ Stratified analyses showed that similar results were also found in different populations. This study showed that the monocyte-to-HDL-C ratio was negatively associated with BMD and the risk of osteopenia and osteoporosis in females. The monocyte-to-HDL-C ratio may be a new marker of osteoporosis or osteopenia.
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Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), induced by sepsis, is predominantly caused by inflammation injury. However, there is no clear consensus on how to regulate the inflammatory response. The TNF pathway is one of the primary inflammatory pathways activated in sepsis. cIAP1/2, an essential E3 ubiquitin ligase in the TNF pathway, plays a pivotal role in positively regulating the activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways to promote inflammation while inhibiting apoptosis. ⋯ Our study shows that cIAP1/2 expression increased in the lung tissue of a CLP rat ALI model. Inhibiting cIAP1/2 with AZD5582, a second mitochondria-derived activator of caspases (SMAC) mimetic, induced increased apoptosis and reduced lung injury. Therefore, inhibiting cIAP1/2 can alleviate sepsis-induced ALI, providing a new target for regulating organ damage induced by sepsis-induced inflammatory responses.
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The FK506-binding protein (FKBP5) plays significant roles in mediating stress responses by interacting with glucocorticoids, participating in adipogenesis, and influencing various cellular pathways throughout the body. In this review, we described the potential role of FKBP5 in the pathogenesis of two common chronic liver diseases, metabolic dysfunction-associated steatotic liver disease (MASLD), and alcohol-associated liver disease (ALD). We provided an overview of the FK-binding protein family and elucidated their roles in cellular stress responses, metabolic diseases, and adipogenesis. We explored how FKBP5 may mechanistically influence the pathogenesis of MASLD and ALD and provided insights for further investigation into the role of FKBP5 in these two diseases.
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Dysregulated cholesterol metabolism represents an increasingly recognized feature of autism spectrum disorder (ASD). Children with fetal valproate syndrome caused by prenatal exposure to valproic acid (VPA), an anti-epileptic and mood-stabilizing drug, have a higher incidence of developing ASD. However, the role of VPA in cholesterol homeostasis in neurons and microglial cells remains unclear. ⋯ VPA exposure significantly reduced protein levels of ABCA1 in a dose-dependent manner, but increased the ABCG1 protein level at the highest dose in SH-SY5Y cells. In addition, VPA treatment significantly increased cholesterol efflux in SH-SY5Y, but had no impact on efflux in HMC3. VPA differentially controls the expression of ABCA1 and ABCG1, but regulation at the transcriptional and translational levels are not consistent and changes in the expression of these genes do not correlate with cholesterol efflux in vitro.