Research progress of SREBP and its role in the pathogenesis of autoimmune rheumatic diseases.

Autoimmune rheumatic diseases comprise a group of immune-related disorders characterized by non-organ-specific inflammation. These diseases include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, among others. Typically involving the hematologic system, these diseases may also affect multiple organs and systems. The pathogenesis of autoimmune rheumatic immune diseases is complex, with diverse etiologies, all associated with immune dysfunction. The current treatment options for this type of disease are relatively limited and come with certain side effects. Therefore, the urgent challenge remains to identify novel therapeutic targets for these diseases. Sterol regulatory element-binding proteins (SREBPs) are basic helix-loop-helix-leucine zipper transcription factors that regulate the expression of genes involved in lipid and cholesterol biosynthesis. The expression and transcriptional activity of SREBPs can be modulated by extracellular stimuli such as polyunsaturated fatty acids, amino acids, glucose, and energy pathways including AKT-mTORC and AMP-activated protein kinase (AMPK). Studies have shown that SREBPs play roles in regulating lipid metabolism, cytokine production, inflammation, and the proliferation of germinal center B (GCB) cells. These functions are significant in the pathogenesis of rheumatic and immune diseases (Graphical abstract). Therefore, this paper reviews the potential mechanisms of SREBPs in the development of SLE, RA, and gout, based on an exploration of their functions.

Artesunate attenuates serum amyloid A-induced M1 macrophage differentiation through the promotion of PHGDH.

Clinical studies indicated that Serum Amyloid A (SAA) might be a promising biomarker for forecasting the activity, severity, and adverse prognosis of systemic lupus erythematosus (SLE). Simultaneously, a positive correlation has been observed between macrophages, Th17 cells, and SLE disease activity, with both these immune cells being affected by SAA. Presently, the relationship between SAA and the aforementioned immune cell types in SLE remains to be elucidated. To discern the immune cell type most closely associated with SAA, we undertook a single-cell RNA sequencing data analysis via the GEO database. Subsequent results revealed a strong association between macrophages and SAA, a relationship further validated through flow cytometry of spleen macrophages in the MRL/lpr model. We discovered that SAA stimulate M1 macrophage differentiation along with the upregulation of pro-inflammatory cytokines such as IL-6 and IL-1ß. Our findings suggest that SAA may promote M1 macrophage differentiation via the downregulation of phosphoglycerate dehydrogenase (PHGDH). Artesunate (ART), primarily utilized for malaria treatment, was shown to inhibit M1 macrophage differentiation and pro-inflammatory cytokine levels via upregulating the PHGDH expression, thereby attenuating the disease activity in SLE.

Lipidomics characterized TAG biosynthesis of developing kernels in three walnut cultivars in Xinjiang region.

Walnut oil with very high proportion of polyunsaturated fatty acids exhibits many health beneficial effects. We hypothesized that the oil composition is led by a special pattern/mechanism for triacylglycerol (TAG) biosynthesis as well as accumulation in walnut kernel during embryo development. To test this hypothesis, shotgun lipidomics was performed for class-targeted lipid analysis (including TAG, phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid, phosphatidylglycerol, phosphatidylinositol, and lysophosphatidylcholine species) in walnut kernels from three cultivar collected at three critical stages of embryo development. The results indicated that TAG synthesis in the kernel happened before 84 days after flowering (DAF) and was significantly enhanced between 84 and 98 DAF. Moreover, TAG profile was changing along with DAFs due to the increased composition of 18:1 FA in TAG pool. Moreover, lipidomics also demonstrated that the enhanced acyl editing was responsible for the flux of FA through phosphatidylcholine for eventual TAG synthesis. Therefore, TAG biosynthesis in walnut kernel was characterized directly from lipid metabolism.

An ocular adverse event in temporal association with COVID-19 vaccination in a patient with systemic lupus erythematosus: a case report.

After the COVID-19 pandemic, vaccines using inactivated viruses have attracted worldwide attention for the prevention of infectious diseases. Here, we report a patient who suffered from Systemic Lupus Erythematosus (SLE) for six years and developed ocular symptoms within 72 hours after being vaccinated for COVID-19. The patient presented bilateral conjunctival congestion, eyelid edema with pruritus, and suffered from severe headaches. Recovery occurred within 10 days after the onset of symptoms after treatment with anti-infection drugs. The early identification and extensive assessment of side effects help ensuring effective vaccine safety monitoring.