Little work is done to developAloe vera(AV) using probiotics. To explore the potential benefits, the antioxidant effects and the antibacterial effects on foodborne pathogens ofAloefermentation supernatant were evaluated in vitro. Our results indicated that theAloefermentation supernatant fermented byLactobacillus plantarumHM218749.1 had very strong scavenging capacities of the DPPH (86%),O2•-(85%),OH•(76%), andFe2+chelation (82%) and reducing powers (242.5 mg/L), and the inhibition zones forSalmonella typhimurium,Salmonella enteritidis,Shigella flexneri,Escherichia coli,Listeria monocytogenes,S. dysenteriae301,Staphylococcus aureusCowan1, andPropionibacterium acneswere 16, 15, 19, 20, 21, 20, and 27 mm. Moreover, the low concentration ofAloefermentation supernatant had significantly reduced the production of IL-1β, TNF-α, and IL-6 in both mRNA and protein levels (P<0.01). Therefore, theAloefermentation supernatant can be used as functional beverage or cosmetic ingredients to guard human intestinal health, delaying senescence, and prevent chronic diseases.

CD38 was first identified as a lymphocyte-specific antigen and then has been found to be widely expressed in a variety of cell types. The functions of CD38 are involved in numerous biological processes including immune responses. Here, we showed the downregulations of both TLR2 mRNA and protein in macrophages from CD38^−/− mice and in CD38 knockdown RAW264.7 cells. Several NF-κB-binding motifs in the promoter region of the TLR2 gene were identified by the bioinformatics analysis and were confirmed by the luciferase activity assay with the different truncated TLR2 promoters. CD38 deficiency resulted in the reduction of NF-κB p65 and acetyl-NF-κB p65 (Ac-p65) levels as determined by Western blot. The expression of Sirt1 did not change, but an increased activity of Sirt1 was observed in CD38-deficient macrophages. Inhibition of the Sirt1/NF-κB signaling pathway resulted in downregulation of TLR2 expression in RAW264.7 cells. However, re-expression of CD38 in the knockdown clones reversed the effect on Sirt1/NF-κB/TLR2 signaling, which is NAD-dependent. Moreover, the inflammatory cytokines including G-CSF, IL-1alpha, IL-6, MCP-1, MIP-1alpha, and RANTES were increased in CD38 knockdown RAW264.7 cells. Taken together, our data demonstrated that CD38 deficiency enhances inflammatory response in macrophages, and the mechanism may be partly associated with increased Sirt1 activity, which promoted NF-κB deacetylation and then inhibited expression of the TLR2 gene. Obviously, our study may provide an insight into the molecular mechanisms in CD38-mediated inflammation.

Recent studies have highlighted the critical role of renal tubular epithelial cell (TEC) damage in the progression of diabetic kidney disease (DKD), where lactate accumulation is closely associated with TEC injury despite unclear mechanisms. This study demonstrates that TRIM65 knockout exacerbates diabetic kidney damage, while TEC-specific overexpression of TRIM65 ameliorates injury. Mechanistically, TRIM65 suppresses ferroptosis by targeting iron-responsive element binding protein 2 (IREB2) for ubiquitin-mediated degradation while also inhibiting glycolysis through ubiquitination and degradation of pyruvate dehydrogenase kinase 4, a key glycolytic regulator. Notably, lactate promotes p300-mediated lactylation of TRIM65 at lysine 206 (K206), which reduces ubiquitin ligase activity. Supplementation of wild-type TRIM65 reverses kidney damage in knockout mice, and overexpression of the lactylation-defective K206R mutant further enhances protective effects against DKD. These findings reveal that lactate-induced lactylation of TRIM65 at K206 impairs its dual regulatory roles in inhibiting ferroptosis and glycolysis, thereby driving DKD progression and identifying therapeutic targets.

Osteopontin (OPN) is reported to be associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the function of OPN in NAFLD is still inconclusive. Therefore, our aim in this study was to evaluate the role of OPN in NAFLD and clarify the involved mechanisms.

Chronic inflammatory diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), atherosclerosis, and inflammatory bowel disease (IBD), pose major global health concerns. These disorders are marked by persistent inflammation, immune system dysfunction, tissue injury, and fibrosis, ultimately leading to severe organ dysfunction and diminished quality of life. Osteopontin (OPN), a multifunctional extracellular matrix protein, plays a crucial role in immune regulation, inflammation, and tissue remodeling. It promotes immune cell recruitment, stimulates pro-inflammatory cytokine production, and contributes to fibrosis through interactions with integrins and CD44 receptors. Additionally, OPN activates key inflammatory pathways, including NF-κB, MAPK, and PI3K/Akt, further aggravating tissue damage in chronic inflammatory conditions. Our review highlights the role of OPN in chronic inflammation, its potential as a biomarker, and its therapeutic implications. We explore promising preclinical approaches, such as monoclonal antibodies, small molecule inhibitors, and natural compounds like curcumin, which have demonstrated potential in mitigating OPN-driven inflammation. However, challenges persist in selectively targeting OPN while maintaining its essential physiological roles, including bone remodeling and wound healing. Our review offers insights into therapeutic strategies and future research directions.