Interleukin-22 inhibits cardiac fibrosis by regulating fibroblast metabolic reprogramming in myocardial infarction.

Cardiac fibrosis, a significant characteristic of cardiovascular diseases, leads to ventricular remodeling and impaired cardiac function. In this study, we aimed to investigate the role of Interleukin-22 (IL-22) in myocardial fibrosis following myocardial infarction (MI) and to explore the underlying metabolic mechanisms. Here we analyzed the single-cell sequencing data and found that the level of aerobic glycolysis was significantly higher in cardiac fibrosis in MI patient, which we validated through in vivo experiments. Utilizing MI mouse model, these experiments revealed decreased serum IL-22 levels and increased levels of AngII and TGF-ß1. However, treatment with exogenous IL-22 reversed these changes, reduced infarct size, and fibrosis. In vitro experiments demonstrated that IL-22 inhibited AngII-induced fibroblast-to-myofibroblast transition (FMT) by suppressing the expression of α-SMA, Cola1, and Cola3. Metabolic analysis indicated that IL-22 decreased the expression of glycolytic enzymes and reduced lactate production in cardiac fibroblasts. Further in vivo experiments confirmed the inhibitory effect of IL-22 on Pyruvate kinase isoform M2 (PKM2) levels in heart tissue. Additionally, IL-22 activated the c-Jun N-terminal kinase (JNK) pathway, while inhibition of JNK partially reversed IL-22's effect on PKM2 activity. These findings suggest that IL-22 mitigates cardiac fibrosis and FMT by inhibiting aerobic glycolysis by activating the JNK/PKM2 pathway. Our study highlights IL-22 as a potential therapeutic target for myocardial fibrosis and cardiovascular diseases, providing insights into its role in regulating fibrosis and glycolysis. These findings pave the way for developing targeted therapies and investigating additional metabolic pathways for improved treatment outcomes in the field of cardiovascular diseases.

Spatiotemporal development and the regulatory mechanisms of cardiac resident macrophages: Contribution in cardiac development and steady state.

Cardiac resident macrophages (CRMs) are integral components of the heart and play significant roles in cardiac development, steady-state, and injury. Advances in sequencing technology have revealed that CRMs are a highly heterogeneous population, with significant differences in phenotype and function at different developmental stages and locations within the heart. In addition to research focused on diseases, recent years have witnessed a heightened interest in elucidating the involvement of CRMs in heart development and the maintenance of cardiac function. In this review, we primarily concentrated on summarizing the developmental trajectories, both spatial and temporal, of CRMs and their impact on cardiac development and steady-state. Moreover, we discuss the possible factors by which the cardiac microenvironment regulates macrophages from the perspectives of migration, proliferation, and differentiation under physiological conditions. Gaining insight into the spatiotemporal heterogeneity and regulatory mechanisms of CRMs is of paramount importance in comprehending the involvement of macrophages in cardiac development, injury, and repair, and also provides new ideas and therapeutic methods for treating heart diseases.

Unveiling immune-metabolic interaction in Atherosclerosis via Comprehensive Landscape of Hub Genes and Immune Microenvironment.

OBJECTIVE: Atherosclerosis (AS) as a major cause of cardiovascular diseases, is considered a chronic inflammatory disease and accelerates by inflammation, lipid metabolism disorder and other mechanisms. AS pathogenesis and its relationship with immune regulation and metabolic interactions is still not fully elucidated. The purpose of this study is to delve into the correlation between mitochondrial metabolism and immunity in AS, and identify potential therapeutic targets for clinical treatment. METHODS: Hub genes associated with mitochondrial metabolism and the pathogenesis of AS were identified by performing differentially expressed genes (DEGs) analysis and Weighted Gene Co-expression Network Analysis (WGCNA) based on two gene expression datasets (GSE100927 and GSE43292). And the biological processes and pathways of DEGs were determined through gene ontology (GO) and Gene Set Enrichment Analysis (GSEA) analysis. Then stepwise regression, random forest, and Lasso regression machine learning were used to evaluate the diagnostic value of hub genes. After that, the immune infiltration and single cell sequencing dataset GSE184073 were analyzed, and the immune cell composition in peripheral blood from AS patients using Mass Cytometry were detected to further consider the influence of immunoregulation. RESULTS: Ten hub genes associated with mitochondrial metabolism and AS pathogenesis were identified, including NDUFS4, AIFM3, IDUA, TNF, CHKA, SLC11A1, SLC35C1, SLC37A2, ARSB, SLC16A5. GO and GSEA analysis showed their correlation with immunity and inflammation. Lasso regression revealed that TNF and ARSB had relatively good diagnostic performance. Further exploration was conducted on the expression of these hub genes in the immune microenvironment and their correlation with different immune factors. Mass cytometry demonstrated the influence of the vascular immune microenvironment on the pathogenesis of AS. CONCLUSIONS: Our study provides a more comprehensive understanding of the complex relationships between immune and metabolic factors and their impact on the microenvironment of AS. The identification of hub genes in AS may provide new targets for therapeutic intervention.

S1PR1-dependent migration of ILC3s from intestinal tissue to the heart in a mouse model of viral myocarditis.

Type 3 innate lymphocytes have recently been reported as key factors in inflammatory diseases, but their role in viral myocarditis is unclear. By flow cytometry, coxsackievirus B3-induced myocarditis mice were detected to increase the number of type 3 innate lymphocytes, and their main type was NKp46+ type 3 innate lymphocytes. In contrast, application of CD90.2 neutralizing antibody in T-cell-deficient mice reduced the number of innate lymphocytes and improved myocarditis. Innate lymphocytes from CD45.1 mouse intestinal lamina propria lymphocytes were adoptively transferred into recipient mice, and a comparable proportion of CD45.1+ cells were observed in the hearts of coxsackievirus B3-infected recipient mice. The upregulation of S1PR1, KLF2, CXCR6, and CXCL16 in the hearts of coxsackievirus B3-infected mice, as well as the greatly reduced numbers of innate lymphocytes infiltrating the hearts after S1PR1 inhibition, suggests that intestinal innate lymphocytes may migrate to the hearts via the CXCL16/CXCR6 axis. Taken together, our results demonstrate that increased type 3 innate lymphocytes in the heart during viral myocarditis may contribute to inflammatory progression and that this increased population of type 3 innate lymphocytes likely originates from the intestine.

Construction of magnetic lignin-based adsorbent and its adsorption properties for dyes.

The magnetic lignin-based adsorbent (Fe3O4/C-ACLS) has been successfully prepared and applied to adsorbing azo dyes Congo red, Titan yellow and Eriochrome blue black R. The samples were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), X-ray powder diffraction (XRD), vibration sample magnetometer (VSM), Raman spectroscopy and elemental analysis. In the process of adsorption, five kinds of influencing factors and recycling regeneration were discussed, and the adsorption mechanisms such as kinetics, isotherm, thermodynamics were explored. The results show that Fe3O4/C-ACLS can remove 98%, 92% and 99% of Congo red, Titan yellow and Eriochrome blue black R, respectively. Under the same conditions, the removal rate was 87%, 84% and 88% after 5 times adsorption cycle, respectively. Pseudo-first-order, pseudo-second-order kinetics, Elovich model and intraparticle diffusion model were studied, and the results show that the adsorption process conforms to pseudo-second-order kinetics model, and the diffusion rate is controlled by many steps. The results of isotherm model and thermodynamics show that the adsorption process is consistent with Langmuir model and is mainly a spontaneous chemical endothermic process of monolayer.