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Prevention and treatment of atherosclerosis (AS) by targeting the inflammatory response in vascular endothelial cells has attracted much attention in recent years. Laminar shear stress (LSS) has well-recognized anti-AS properties, however, the exact molecular mechanism remains unclear. In this study, we found that LSS could inhibit the increased expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and matrix metallopeptidase-9 (MMP-9) caused by TNF-α in an autophagy-dependent pathway in human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs). Whole-transcriptome sequencing analysis revealed that erythropoietin-producing hepatocyte receptor B2 (EPHB2) was a key gene in response to LSS. Moreover, co-immunoprecipitation assay indicated that LSS could enhance the EPHB2-mediated nuclear translocation of high mobility group box-1 (HMGB1), which interacts with Beclin-1 (BECN1) and finally leads to autophagy. Simultaneously, we identified an LSS-sensitive long non-coding RNA (lncRNA), LOC10798635, and constructed an LSS-related LOC107986345/miR-128-3p/EPHB2 regulatory axis. Further research revealed the anti-inflammatory effect of LSS depends on autophagy activation resulting from the nuclear translocation of HMGB1 via the LOC107986345/miR-128-3p/EPHB2 axis. Our study demonstrates that LSS could regulate the expression of EPHB2 in HAECs, and the LOC107986345/miR-128-3p/EPHB2 axis plays a vital role in AS development. The transcriptional response to laminar sheer stress in human aortic endothelial cells reveals a pathway leading to inhibition of endothelial cell inflammation by autophagy induction. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the main cause of cardiovascular disease, and fluid shear stress is a key factor regulating its occurrence and development. Oscillatory shear stress (Oss) is an important pro-atherosclerosis factor. Oss mainly occurs in areas that are susceptible to atherosclerosis, but the exact mechanism of atherosclerosis induction remains unclear. Therefore, starting from the atheroprone phenotype that Oss stimulates abnormal vascular endothelial cell proliferation, this study aimed to reveal the underlying mechanism of Oss-induced atherosclerosis formation and to identify new targets for the prevention and treatment of atherosclerosis. In this study, the gene encoding thioredoxin reductase 1 (TXNRD1), which is closely related to atherosclerosis development and cell proliferation, was screened by analyzing the transcriptome sequencing data of static and Oss-treated human aortic endothelial cells (HAECs). Moreover, this study successfully verified that TXNRD1 mRNA and protein were significantly upregulated in Oss-treated HAECs. Oss significantly promoted the proliferation, migration, and tube formation of HAECs, whereas TXNRD1 knockdown impaired the proliferation, migration, and tube formation of Oss-treated HAECs, and this process was mainly achieved via activation of the apoptosis pathway. To further clarify whether Oss-sensitive TXNRD1 affects the apoptosis rate and proliferative ability of HAECs by regulating the endothelial nitric oxide synthase (eNOS) pathway, we used NG-nitro-L-arginine methyl ester (L-NAME) to inhibit eNOS activity and nitric oxide (NO) production. L-NAME significantly reversed the promoting effect of TXNRD1 knockdown on Oss-treated HAEC apoptosis, and it also abolished the inhibitory effect of TXNRD1 knockdown on the proliferation and S + G2 phase cell mass of Oss-treated HAECs. In conclusion, this study showed that TXNRD1 knockdown inhibited the proliferation of HAECs exposed to Oss by activating the eNOS/apoptosis pathway, revealing that TXNRD1 is involved in the dysregulation of Oss-induced endothelial cell proliferation. These findings provide new directions and insights into the prevention and treatment of atherosclerosis. • Upregulation of endothelial TXNRD1 expression in response to Oss • TXNRD1 knockdown restored Oss-reduced eNOS phosphorylation and NO production in HAECs. • TXNRD1 knockdown inhibited the proliferation of HAECs exposed to Oss through activation of the eNOS/apoptosis pathway. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a highly disabling autoimmune disorder, characterized by the proliferation of Fibroblast-like Synoviocytes (FLSs). Icariin is a prenylated flavonol glycoside extracted from the medical plant Epimedium , which can inhibit the proliferation and migration of FLSs. However, the potential mechanism of icariin to alleviate RA remains unclear. In this study, icariin inhibited the migration and proliferation of FLSs in a concentration-dependent manner, by inducing G2/M phase arrest and apoptosis. Icariin reduced the mitochondrial transmembrane potential, upregulated cytosolic cytochrome c and increased the level of intracellular reactive oxygen species (ROS). In conclusion, icariin inhibited the proliferation of FLSs by interfering with the cell cycle process and inducing cell apoptosis, suggesting its potential use for the treatment of RA. [ABSTRACT FROM AUTHOR]

• Morin hydrate inhibits LPS-induced inflammatory responses in HUVECs. • Morin hydrate inhibits LPS-induced activation of the PI3K/Akt1/NFκB signaling pathway. • Morin hydrate inhibits inflammatory in an autophagy-dependent way. Atherosclerosis (AS) is a chronic inflammatory disease involving blood vessels. Inflammation affects different cells and increases the expression of adhesion molecules. Morin hydrate (MO) is a naturally occurring bioflavonoid with anti-inflammatory and anti-oxidant effects. Although the exact mechanism has not been fully elucidated, MO possibly influences autophagy pathways in immunity and inflammation. In this study, MO showed the potential to inhibit atherosclerotic and promote vascular endothelial autophagy in apolipoprotein E (ApoE)−/− mice with a high-fat diet. Then, we aimed to explore the anti-inflammatory effects of MO in human umbilical vein endothelial cells (HUVECs) and its relationship with autophagy. We found that MO inhibited lipopolysaccharide (LPS)-induced monocyte adhesion and the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and matrix metallopeptidase 9 (MMP-9) in HUVECs. Moreover, MO reduced the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor kappa B (NFκB) signaling pathway. MO induced autophagy by inhibiting the NFκB signaling pathway in normal HUVECs and LPS-stimulated HUVECs. When autophagy was inhibited by 3-methyladenine (3-MA) or small interfering RNA (siRNA), the anti-inflammatory effect of MO was reduced. In conclusion, MO inhibits atherosclerosis in ApoE−/− mice and LPS-induced inflammatory responses by inhibiting the activation of the PI3K/Akt1/NFκB signaling pathway in a NFκB signaling-mediated autophagy way. [ABSTRACT FROM AUTHOR]

• NK92 cells expressing novaferon possessed enhanced cytotoxicity. • NK92-nova possessed activated JAK/STAT signaling pathway. • The cytotoxicity of NK92-nova was partially dependent on the NKG2D/NKG2DL pathway. With significant developments in chimeric antigen receptor T-cell therapy, adoptive immunotherapy has unlocked new levels of treatment for malignancies. Natural killer (NK) cells are promising alternative immune effector cells for this strategy. Multiple anti-tumor therapies are largely dependent on type I interferon (IFN) signaling. Type I IFNs enhance NK cell cytotoxicity. Novaferon (nova) is an unnatural, novel IFN-like protein produced by gene shuffling of IFN-α with strong biological activity. To augment the antitumor activity of NK cells, we generated NK92-nova cells that stably express nova. We found that NK92-nova cells mediated enhanced pan-cancer antitumor activity compared to NK92-vec cells. The increased antitumor activity was associated with the enhanced secretion of cytokines, such as IFN-γ, perforin, and granzyme B. Meanwhile, most of the activating receptors were upregulated in the NK92-nova cells. After co-culture with NK92-nova cells, the expression of NKG2D ligands on the HepG2 cells increased, resulting in an enhanced susceptibility of HepG2 cells to NK92 cell-mediated cytolysis. NK92-nova cells significantly inhibited HepG2 tumor growth in a xenograft model without systemic toxicity. Therefore, NK92-nova cells are a novel and safe strategy for cancer immunotherapy. [ABSTRACT FROM AUTHOR]