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Atherosclerosis (AS) is characterized by dyslipidemia and chronic inflammation. In the high-fat environment, the lipid metabolism of dendritic cells (DCs) is abnormal, which leads to abnormal immune function, promotes the occurrence of immune inflammatory reactions, and promotes the development of AS. Alisol B 23-acetate (23B) is a triterpenoid in the rhizomes of Alisma, which is a traditional Chinese medicine. Here, we identified cholesterol metabolism-related targets of 23B through a virtual screen, and further transcriptome analysis revealed that 23B can change antigen presentation and cholesterol metabolism pathways in cholesterol-loaded DCs. In vitro experiments confirmed that 23B promoted cholesterol efflux from ApoE -/- DCs, reduced the expression of MHC II, CD80, and CD86, and inhibited the activation of CD4 + T cells and the production of inflammatory cytokines IL-12 and IFN-γ. In advanced AS mice, 23B can decrease triacylglycerol (TG) levels and increase high-density lipoprotein-cholesterol (HDL-C) levels in plasma and the expression of cholesterol efflux genes in the aorta. Neither helper T cells 1 (Th1) nor regulatory T cells (Tregs) in peripheral blood changed significantly in the presence of 23B, but 23B reduced the levels of IL-12 and IFN-γ in serum. However, 23B did not change the total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels in serum or lipid accumulation in the aorta. Moreover, 23B did not increase the production of IL-10 and TGF-β1 in vivo or in vitro. These results indicate that 23B promotes cholesterol efflux from DCs, which can improve the immune inflammatory response and contribute to controlling the inflammatory status of AS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Endothelial cells (ECs) are widely distributed inside the vascular network, forming a vital barrier between the bloodstream and the walls of blood vessels. These versatile cells serve myriad functions, including the regulation of vascular tension and the management of hemostasis and thrombosis. Inflammation constitutes a cascade of biological responses incited by biological, chemical, or physical stimuli. While inflammation is inherently a protective mechanism, dysregulated inflammation can precipitate a host of vascular pathologies. ECs play a critical role in the genesis and progression of vascular inflammation, which has been implicated in the etiology of numerous vascular disorders, such as atherosclerosis, cardiovascular diseases, respiratory diseases, diabetes mellitus, and sepsis. Upon activation, ECs secrete potent inflammatory mediators that elicit both innate and adaptive immune reactions, culminating in inflammation. To date, no comprehensive and nuanced account of the research progress concerning ECs and inflammation in vascular-related maladies exists. Consequently, this review endeavors to synthesize the contributions of ECs to inflammatory processes, delineate the molecular signaling pathways involved in regulation, and categorize and consolidate the various models and treatment strategies for vascular-related diseases. It is our aspiration that this review furnishes cogent experimental evidence supporting the established link between endothelial inflammation and vascular-related pathologies, offers a theoretical foundation for clinical investigations, and imparts valuable insights for the development of therapeutic agents targeting these diseases. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is one of the most common chronic diseases, in which inflammatory responses in the articular cavity induce chondrocyte apoptosis and cartilage degeneration. While mechanical loading is reported to mitigate synovial inflammation, the mechanism and pathways for the loading‐driven improvement of OA symptoms remain unclear. In this study, we evaluated the loading effects on M1/M2 polarization of synovial macrophages via performing histology, cytology, and molecular analyses. In the OA group, the cell layer of the synovial lining was enlarged with an increase in cell density. Also, M1 macrophages were polarized and proinflammatory cytokines were increased. In contrast, in the OA group with mechanical loading, cartilage degradation was reduced and synovial inflammation was alleviated. Notably, the M1 macrophages were diminished by mechanical loading, while M2 macrophages were increased. Furthermore, mechanical loading decreased the levels of proinflammatory cytokines, such as interleukin‐1 beta and tumor necrosis factor‐α, and suppressed PI3K/AKT/NF‐κB signaling. Taken together, this study demonstrates that mechanical loading changes the ratio of M1 and M2 macrophages via regulation of PI3K/AKT/NF‐κB signaling and provides cartilage protection in the mouse OA model. [ABSTRACT FROM AUTHOR]

An increasing number of researches have shown that cell metabolism regulates cell function. Dendritic cells (DCs), a professional antigen presenting cells, connect innate and adaptive immune responses. The preference of DCs for sugar or lipid affects its phenotypes and functions. In many diseases such as atherosclerosis (AS), diabetes mellitus and tumor, altered glucose or lipid level in microenvironment makes DCs exert ineffective or opposite immune roles, which accelerates the development of these diseases. In this article, we review the metabolism pathways of glucose and cholesterol in DCs, and the effects of metabolic changes on the phenotype and function of DCs. In addition, we discuss the effects of changes in glucose and lipid levels on DCs in the context of different diseases for better understanding the relationship between DCs and diseases. The immune metabolism of DCs may be a potential intervention link to treat metabolic-related immune diseases. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI), a leading cause of morbidity worldwide, induces mechanical, persistent structural, and metabolic abnormalities in neurons and other brain-resident cells. The key pathological features of TBI include neuroinflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction. These pathological processes persist for a period of time after TBIs. Sirtuins are evolutionarily conserved nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylases and mono-ADP-ribosyl transferases. The mammalian sirtuin family has seven members, referred to as Sirtuin (SIRT) 1–7. Accumulating evidence suggests that SIRT1 and SIRT3 play a neuroprotective role in TBI. Although the evidence is scant, considering the involvement of SIRT2, 4–7 in other brain injury models, they may also intervene in similar pathophysiology in TBI. Neurodegenerative diseases are generally accepted sequelae of TBI. It was found that TBI and neurodegenerative diseases have many similarities and overlaps in pathological features. Besides, sirtuins play some unique roles in some neurodegenerative diseases. Therefore, we propose that sirtuins might be a promising therapeutic target for both TBI and associated neurodegenerative diseases. In this paper, we review the neuroprotective effects of sirtuins on TBI as well as related neurodegeneration and discuss the therapeutic potential of sirtuin modulators. [ABSTRACT FROM AUTHOR]

Whether there was an interaction effect between depressive symptoms and inflammation on the occurrence of cardiovascular diseases (CVDs) was unclear. In this cross-sectional study, 3346 participants in the National Health and Nutrition Examination Survey (NHANES) were included. Multivariable regression analysis was performed to explore the associations of depressive symptoms or inflammation with CVDs. The attributable proportion of interaction (API), and synergy index (SI) were applied for evaluating the statistical significance of the interaction effect. Depressive symptoms were associated with 2.31-fold risk of CVDs [odds ratio (OR) = 2.31, 95 % confidence interval (CI): 1.47–3.62). The increased risk of CVDs was observed in people with neutrophil to lymphocyte ratio (NLR) ≥1.88 group (OR = 1.36, 95%CI: 1.01–1.85) and neutrophil/[white blood cell (WBC)-neutrophil] ≥1.35 (OR = 1.52, 95%CI: 1.12–2.07) after adjusting for confounders. The interaction effect of depressive symptoms and high NLR on the risk of CVDs was statistically significant with an OR value of 2.60 (95%CI: 1.43–4.70) compared to low NLR and no depressive symptoms group after adjusting for confounders. The API was 0.66 (95%CI: 0.44–0.89) and SI was 4.23 (95%CI: 2.08–8.59). The interaction effect of depressive symptoms and high neutrophil/(WBC-neutrophil) was associated with the risk of CVDs compared to low neutrophil/(WBC-neutrophil) and no depressive symptoms group (OR = 3.59, 95%CI: 2.00–6.45). The API was 0.78 (95%CI: 0.63–0.93) and SI was 6.75 (95%CI: 3.55–12.82). There was an interaction effect of depressive symptoms and inflammation on the occurrence of CVDs. • The increased risk of CVDs was observed in people with NLR ≥ 1.88. • The increased risk of CVDs was found in people with neutrophil/ (WBC-neutrophil) ≥1.35. • The interaction of depressive symptoms and high NLR on the risk of CVDs was significant. [ABSTRACT FROM AUTHOR]

Oxymatrine (OMT) is a quinoline alkaloid isolated from the root of the Sophora flavescens that has a variety of biological activities. However, the effect and potential mechanism of OMT on isoproterenol (ISO)-induced heart failure (HF) are not clear. In this study, we found that OMT improved the survival of HL-1 cells induced by ISO. We also demonstrated that OMT significantly inhibited the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). OMT decreased the levels of the TLR4 and reduced the phosphorylation levels of nuclear factor-κB (NF-κB) inhibitor (IκB), p65, c-Jun N-terminal kinases (JNK) and p38. The inhibitory effect of the TLR4 inhibitor TAK242 on HL-1 cells was evaluated. The results showed that the effect of OMT on the phosphorylation levels of IκBα and p65 was enhanced in HL-1 cells treated with TAK242. Using animal models, OMT significantly reduced ISO-induced cardiac injury, myocardial necrosis, interstitial edema, and fibrosis. In addition, OMT attenuated TNF-α and IL-6 and inhibited the expression of TLR4/NF-κB and MAPK pathway-related proteins. This finding suggests that OMT may alleviate HF by interfering with the TLR4/NF-κB and MAPK pathways. • The prognosis of heart failure is poor, which affects physical and mental health. • TLR4/NF-κB and MAPK signal pathways play an important role in heart failure. • Oxymatrine has a therapeutic effect on isoproterenol-induced heart failure. [ABSTRACT FROM AUTHOR]