This study aims to evaluate the therapeutic effects of sodium octanoate (SO), a medium-chain fatty acid salt, on SIMD in a murine model and to explore its underlying mechanisms. Male mice were subjected to sepsis models through two methods: intraperitoneal injection of lipopolysaccharide (LPS) and cecal ligation and punction (CLP). Mice received interval doses of SO every 2 hours or 4 hours for a total of six times or three times after LPS treatment. The relationship between SO and G protein-coupled receptor 84 (GPR84) was evaluated through GEO data analysis and molecular docking studies. DBA/2 mice were used to study the role of the GPR84 protein in the SO-mediated protection. Energy metabolomics was utilized to comprehensively assess the impact of SO on the levels of cardiac energy metabolic products in septic mice. histone modification identification techniques were used to further identify the specific sites of histone modification in the hearts of SO-treated septic mice. SO treatment significantly improved myocardial contractile function, restored the oxidative stress imbalance and enhanced the myocardium's resistance to oxidative injury. SO significantly promotes the expression of GPR84. The loss of GPR84 function markedly attenuates the protective effects of SO. SO enhanced myocardial energy metabolism by promoting the synthesis of acetyl-CoA and upregulating genes involved in fatty acid β-oxidation which were abolished by medium-chain acyl-CoA dehydrogenase (MCAD) knockdown. SO induced histone acetylation, particularly at H3K123 and H3K80. Our study demonstrates that SO exerts protective effects against SIMD through both GPR84-mediated anti-inflammatory and antioxidant actions and GPR84-independent enhancement of myocardial energy metabolism, possibly mediated by MCAD.

Psoriasis is an inflammatory dermatological condition challenging to treat and prone to recurrence. The pathogenesis of psoriasis is closely associated with metabolic disorders, while therapies targeting the dysregulated metabolism in psoriasis remain limited. Therefore, exploring the pathogenesis of psoriasis and identifying potential metabolic therapeutic targets is imperative. In this study, potential biomarkers for clinically targeted metabolic therapies in patients with psoriasis are aimed to be identified. RNA‐sequencing analysis is performed on metabolism‐related genes to identify differentially expressed metabolism‐related genes. Then, various bioinformatics analyses and comprehensive functional experiments are conducted to verify the roles of the identified genes. A key gene SLC16A10 is identified with significant diagnostic and therapeutic potential for psoriasis. SLC16A10 is likely involved in arachidonic acid metabolism in keratinocytes through regulating thyroid hormone homeostasis, contributing to the development of psoriasis. SLC16A10 represents a promising therapeutic target for guttate psoriasis and can improve the outcomes of existing immune‐targeted therapeutic agents. Comprehensive in vitro and in vivo experiments confirm that SLC16A10 downregulation alleviates the severity of psoriasis and hyperinflammation. Moreover, SLC16A10 may induce one of the sequelae of psoriasis, namely post‐inflammatory hypopigmentation, by inhibiting melanogenesis. These findings demonstrate the potential of SLC16A10 as a diagnostic biomarker and therapeutic target for psoriasis.

Background Acute compartment syndrome (ACS), a well-known complication of musculoskeletal injury, results in muscle necrosis and cell death. Embryonic stem cell-derived mesenchymal stem cells (ES-MSCs) have been shown to be a promising therapy for ACS. However, their effectiveness and potentially protective mechanism remain unknown. The present study was designed to investigate the efficacy and underlying mechanism of ES-MSCs in ACS-induced skeletal muscle injury. Method A total of 120 male Sprague–Dawley (SD) rats underwent 2 hours of intracompartmental pressure elevation by saline infusion into the anterior compartment of the left hindlimb to establish the ACS model. ES-MSCs were differentiated from the human embryonic stem cell (ES) line H9. A dose of 1.2×10⁶ of ES-MSCs was intravenously injected during fasciotomy. Post-ACS assessments included skeletal edema index, serum indicators, histological analysis, apoptosis, fibrosis, regeneration, and functional recovery of skeletal muscle. Then, fluorescence microscopy was used to observe the distribution of labeled ES-MSCs in vivo, and western blotting and immunofluorescence analyses were performed to examine M2 macrophage infiltration in skeletal muscle. Finally, we used liposomal clodronate to deplete macrophages and reassess skeletal muscle injury in response to ES-MSC therapy. Result ES-MSCs significantly reduced systemic inflammatory responses, ACS-induced skeletal muscle edema and cell apoptosis. In addition, ES-MSCs inhibited skeletal muscle fibrosis and increased regeneration and functional recovery of skeletal muscle after ACS. The beneficial effects of ES-MSCs on ACS-induced skeletal muscle injury were accompanied by an increase in CD206-positive M2 macrophage polarization. After depleting macrophages with liposomal clodronate, the beneficial effects of ES-MSCs were abolished. Conclusion Our findings suggest that embryonic stem cell-derived mesenchymal stem cells infusion could effectively alleviate ACS-induced skeletal muscle injury, in which the protective effects were related to M2 macrophage polarization.