Macrophage Gpx4 deficiency aggravates foam cell formation by regulating the expression of scavenger receptors, ABCA1, and ABCG1.

Macrophage-derived foam cell formation is critical for the initiation and development of atherosclerosis, which contributes to atherosclerotic cardiovascular disease (ASCVD). Glutathione peroxidase 4 (GPX4), a crucial ferroptosis regulator, protects cells from excessive oxidative stress by neutralizing lipid peroxidation. However, the role of macrophage GPX4 in foam cell formation remains unknown. We reported that oxidized low-density lipoprotein (oxLDL) upregulated GPX4 expression in macrophages. Using the Cre-loxP system, we generated myeloid cell-specific Gpx4 knockout (Gpx4myel-KO ) mice. Bone marrow-derived macrophages (BMDMs) were isolated from WT and Gpx4myel-KO mice and incubated with modified low-density lipoprotein (LDL). We found that Gpx4 deficiency promoted foam cell formation and increased the internalization of modified LDL. Mechanistic studies unveiled that Gpx4 knockout upregulated scavenger receptor type A and LOX-1 expression and downregulated ABCA1 and ABCG1 expression. Collectively, our study lends a novel insight into the role of GPX4 in suppressing macrophage-derived foam cell formation and suggests GPX4 as a promising therapeutic target to interfere with atherosclerosis-related diseases.

MiR-129-5p prevents depressive-like behaviors by targeting MAPK1 to suppress inflammation.

Depression is a complex etiological disease with limited effective treatments. Previous studies have indicated the involvement of miRNAs in the pathophysiology of mood disorders. In this study, we focused on the role and mechanisms of miR-129-5p in depression by successfully constructing mice models of depressive-like behavior via chronic unpredictable mild stress (CUMS) exposure. Herein, miR-129-5p expression was decreased in the hippocampus of CUMS mice model. Upregulation of miR-129-5p reduced depressive-like behaviors of CUMS mice, as revealed in sucrose preference test, novelty suppressed feeding test, forced swim test, tail suspension test, social interaction test. MiR-129-5p upregulation decreased the concentrations and protein levels of proinflammatory cytokines (IL-6, IL-1ß and TNF-α), indicating the inhibitory role of miR-129-5p in inflammation. Furthermore, miR-129-5p was identified to target MAPK1. MAPK1 was negatively regulated by miR-129-5p, and silencing of MAPK1 attenuated depressive-like behaviors in CUMS mice. Moreover, MAPK1 downregulation decreased inflammation in the hippocampus of CUMS mice. Upregulation of MAPK1 reversed the suppressive effects of miR-129-5p upregulation on depressive-like behaviors and inflammation in CUMS mice. In conclusion, the current study identified that miR-129-5p reduces depressive-like behaviors and suppresses inflammation by targeting MAPK1 in CUMS mice, offering a novel molecular interpretation for depression prevention.

Pristane attenuates atherosclerosis in Apoe-/- mice via IL-4-secreting regulatory plasma cell-mediated M2 macrophage polarization.

Atherosclerosis, an inflammatory progressive vascular disease, causes heart disease and stroke worldwide. B cells with immune suppressive functions have been implicated in autoimmune, inflammatory, and cardiovascular diseases. However, the precise role of regulatory B cells and the interaction with macrophages in atherosclerosis remains undefined. In our study, eight-week-old female apolipoprotein E null (Apoe-/-) mice were treated with a single dose of vehicle or pristane and then placed on an atherogenic diet for 12 weeks. We found that pristane decreased atherosclerotic lesion formation and increased stability of atherosclerotic plaques in Apoe-/- mice. We also observed lower frequencies of CD19+ B cells but higher frequencies of CD138+ plasma cells and CD206+ M2 macrophages in Apoe-/- mice treated with pristane. Importantly, pristane inhibited immune cell infiltration into the vascular wall. The upregulation of IL-4 in bone-marrow CD138+ plasma cells from pristane-treated Apoe-/- mice was demonstrated by RNA-sequencing (RNA-seq). Consistently, oxidized low-density lipoprotein (oxLDL) directly induced IL-4-secreting plasma cell generation in vitro. In a co-culture system incubating an anti-IL-4 neutralizing antibody, the results showed that oxLDL-induced CD138+ plasma cells could boost M2 macrophage polarization via IL-4 secretion. Our data demonstrate an unexpected role that pristane induces IL-4-producing CD138+ regulatory plasma cell generation and M2 polarization to protect atherosclerosis development.

[Intelligent peritoneal dialysis system for the treatment of renal failure].

Peritoneal dialysis is an important approach to the treatment of renal failure diseases such as acute renal failure, chronic renal failure and uremia. In this paper are presented the application of the multifunction squirm pump developed by authors, the use of PLC and single-chip to control harmonically, and the instituition of full automatic dialysis therapy. Man-machine interface with integrative touch liquid crystal display is adopted in the system, and Chinese interface is used to display and operate so that user can manipulate it in a guiding way. Hence, the whole process is simple and clear. At the same time, it is very easy to set dialysis parameters suited for medical treatment demands of all kinds of patients. Through squirm pump, electric valve, electronic weighing system and electrical heating system, the accurate control of input and output dialysis volumes, flow velocities, temperature, and other parameters are achieved and automatic alarm function is also implemented. Meanwhile, particular intelligent card system that can access automatically the user's treatment information is syncretized, which is convenient for doctor to make a diagnosis and give treatment or to carry out remote treatment. This system plays an important role in the improvement of peritoneal dialysis technique for renal failure treatment and clinical implementation.