Serum lipidomic study of long-chain fatty acids in psoriasis patients prior to and after anti-IL-17A monoclonal antibody treatment by quantitative GC‒MS analysis with in situ extraction.

BACKGROUND: Long-chain fatty acids (LCFAs) are involved in regulating multiple physiological processes as signalling molecules. Gas chromatography-mass spectrometry (GC-MS) is widely used to quantify LCFAs. However, current quantitative methods for LCFAs using GC-MS have demonstrated complicated issues. Psoriasis is a chronic inflammatory skin disease, and its pathogenesis may be related to the overproduction of interleukin-17A (IL-17A). Clinical efficacy of anti-IL-17A monoclonal antibody (mAb) treatment in psoriasis patients has been demonstrated. Recent studies suggest that LCFAs play varying roles in the pathogenesis of psoriasis. However, more comprehensive research is needed to illuminate the mechanism of LCFAs in psoriasis. METHODS: The established in situ derivatization method for analysing LCFAs with a GC-MS platform was utilized to conduct serum lipidomics analysis of healthy volunteers and psoriasis patients receiving pretherapy and posttreatment with of anti-IL-17A mAb. Imiquimod (IMQ)-treated wild type (WT) and T-cell receptor delta chain knock-out (Tcrd-/-) mice were used to investigate the correlation between IL-17A and abnormal changes in LCFAs in psoriasis patients. RESULTS: A rapid and sensitive in situ extraction derivatization method for quantifying LCFAs using GC-MS was established. Serum lipidomic results showed that psoriasis patients had higher levels of saturated fatty acids (SFAs) and ω-6 polyunsaturated fatty acids (PUFAs) but lower levels of monounsaturated fatty acids (MUFAs) and ω-3 PUFAs than healthy individuals, indicating impaired serum LCFA metabolism. Anti-IL-17A mAb treatment affected most of these LCFA changes. Analysis of LCFAs in IMQ-treated mice showed that LCFAs increased in the serum of WT mice, while there were no significant changes in the Tcrd-/- mice. SFAs increased in IMQ-treated WT mice, while MUFAs showed the opposite trend, and PUFAs did not change significantly. CONCLUSIONS: This study presented a dependable method for quantifying LCFAs that enhanced sensitivity and reduced analysis time. The lipidomic analysis results showed that anti-IL-17A mAb not only ameliorated skin lesions in psoriasis patients but also affected abnormal LCFAs metabolism. Furthermore, the study indicated a potential correlation between IL-17A and abnormal LCFA metabolism in psoriasis patients, which was supported by the alterations in serum LCFAs observed in IMQ-treated WT and Tcrd-/- mice.

Tumor-Selective Biodegradation-Regulated Photothermal H2 S Donor for Redox Dyshomeostasis- and Glycolysis Disorder-Enhanced Theranostics.

H2 S-mediated tumor therapy has received great attention due to its unique physiological activity and synergistical enhancement, but suffers from limited H2 S donors with promised biosafety to regulate the H2 S delivery and subsequently the elusive pathway to augment the combined therapy. Herein, a PEGylated porous molybdenum disulfide nanoflower (MSP) with abundant defects is facilely synthesized for tumor-targeted theranostics. MSP possesses good water-dispersity and high photothermal ability, which is used for photoacoustic imaging and photothermal therapy. Interestingly, MSP is selectively degraded upon exposure to superfluous glutathione (GSH) within tumor cells, the mechanism of which is investigated, as a reduction-coordination reaction. This special degradation induces redox dyshomeostasis via GSH depletion for reactive oxygen species-accumulated chemodynamic therapy. Meanwhile, the selective biodegradation of MSP regulates a sustained H2 S release within tumor and achieves a targeted H2 S gas therapy via enhancing the glycolysis to acidify the tumor cells (glycolysis disorder). Synergistically, these performances are further enhanced via near-infrared photothermal heating, where excellent therapeutic outcomes with good biosafety are accomplished in vitro and in vivo. These characteristics, together with the unique biodegradation and no obvious side-effects of the nanoparticles, suggest a potential therapeutic strategy for precise tumor treatments.