In this present study, bioinformatics analysis and the experimental validation method were used to systematically explore the antioxidant activity and anti-inflammatory effect of Lactiplantibacillus plantarum A106, which was isolated from traditional Chinese pickles, on lipopolysaccharide (LPS)-induced RAW264.7 macrophages. L. plantarum A106 had a good scavenging ability for DPPH, ABTS, and hydroxyl radicals. Furthermore, L. plantarum A106 could increase the activity of RAW264.7 macrophages; raise the SOD and GSH levels, with or without LPS sensitization; or decrease the MDA, TNF–α, and IL–6 levels. In order to deeply seek the antioxidant and anti-inflammatory role and mechanism, bioinformatic analysis, including GO, KEGG, and GSEA analysis, was used to conduct an in-depth analysis, and the results showed that the LPS treatment of RAW264.7 macrophages significantly upregulated inflammatory-related genes and revealed an enrichment in the inflammatory signaling pathways. Additionally, a network analysis via the Cytoscape software (version 3.9.1) identified key central genes and found that LPS also disturbed apoptosis and mitochondrial function. Based on the above bioinformatics analysis, the effects of L. plantarum A106 on inflammation-related gene expression, mitochondrial function, apoptosis, etc., were detected. The results indicated that L. plantarum A106 restored the declined expression levels of crucial genes like TNF–α and IL–6; mitochondrial membrane potential; and apoptosis and the expression of apoptosis-related genes, Bcl–2, Caspase–3, and Bax. These results suggest that L. plantarum A106 exerts antioxidant activity and anti-inflammatory effects through regulating inflammatory and apoptosis-related gene expression, restoring the mitochondrial membrane potential.

As the only mammalian appendage capable of complete regeneration, deer antlers serve as an invaluable model to investigate cartilage regrowth, but the underlying mechanism remains unclear. This study revealed that addition of palmitic acid (PA), an abundant long-chain saturated free fatty acid, inhibited the proliferation and hypertrophy of antler chondrocytes while promoting chondrocyte apoptosis. PA treatment activated NOTCH1 signaling and restrained the transport of Ca²⁺ from the cytosol to the endoplasmic reticulum (ER) via RBPJ (recombination signal-binding protein for immunoglobulin kappa J region)-targeted TMTC4 (transmembrane O-mannosyltransferase targeting cadherins 4), resulting in a reduction in ER Ca²⁺. Meanwhile, PA disrupted the structure and function of mitochondria-associated ER membranes (MAMs) via TGM2 (transglutaminase 2) through the cytosolic Ca²⁺-mediated PPP3CB (protein phosphatase 3 catalytic subunit beta)-NFATC2 (nuclear factor of activated T cells cytoplasmic 2) pathway. Further analysis demonstrated that PA induced mitochondrial dysfunction via MAM-mediated mitochondrial Ca²⁺ insufficiency, thereby restricting mitophagy and attenuating lysosomal acidification. This caused the leakage of mitochondrial reactive oxygen species (mtROS) from depolarized mitochondria into the cytosol via the mitochondrial permeability transition pore, thereby inducing lipid peroxidation, while the addition of ROS scavengers prevented the negative effects of chondrocyte proliferation and hypertrophy and protected chondrocytes from apoptosis in the context of PA. Collectively, PA treatment regulated the proliferation, apoptosis and hypertrophy of antler chondrocytes by disrupting MAM function.