Search

Background: Didymin is a dietary flavonoid derived from citrus fruits and has been shown to have extensive biological functions, especially anti-inflammatory effects, but its mechanism is unclear. The purpose of this study was to investigate the potential mechanism of didymin that alleviates ulcerative colitis. Methods and Results: Our results indicated that didymin could alleviate the symptoms of ulcerative colitis, as it inhibited the expressions of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Didymin also promoted the expressions of claudin-1 and zona occludens-1(ZO-1), which are closely related with restoring colon barrier function. Didymin also increased the abundance of Firmicutes and Verrucomicobiota, while decreasing the abundance of Bacteroidota and Proteobacteria. Meanwhile, didymin significantly altered the levels of metabolites related to arginine synthesis and metabolism, and lysine degradation in the colitis mice. Utilizing network pharmacology and molecular docking, our results showed that the metabolites L-ornithine and saccharin could interact with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-κB). In this in vitro study, L-ornithine could reduce the expressions of transcription factors STAT3 and NF-κB, and it also inhibited the expressions of IL-6 and IL-1β in the lipopolysaccharides (LPS) induced in RAW264.7 cells, while saccharin had the opposite effect. Conclusions: Taken together, didymin can regulate gut microbiota and alter metabolite products, which can modulate STAT3 and NF-κB pathways and inhibit the expressions of inflammatory factors and inflammatory response in the DSS-induced colitis mice. [ABSTRACT FROM AUTHOR]

Excessive inflammatory reactions are the most important pathological injury factor in acute lung injury (ALI). Our recent study found that sialic acid had an anti-colitis effect. In this study, the effect of sialic acid (SA) on acute lung inflammation was investigated. A lipopolysaccharide (LPS)-induced ALI animal model and LPS-stimulated HUVEC cell model were used to evaluate the anti-inflammatory effect of SA and study its molecular mechanisms. Compared with the LPS group, the lung index of the SA group decreased from 0.79 ± 0.05% to 0.58 ± 0.06% (LPS + 50 SA) and 0.62 ± 0.02% (LPS + 100 SA), with p < 0.01, suggesting that SA could improve the pulmonary edema of mice and alleviate LPS-induced lung injury. Transcriptome research identified 26 upregulated genes and 25 downregulated genes involved in the protection of SA against ALI. These genes are mainly related to the MAPK and NF-κB signaling pathways. Our study also proved that SA markedly downregulated the expression of inflammatory factors and blocked the JNK/p38/PPAR-γ/NF-κB pathway. Meanwhile, SA treatment also upregulated the expression of HO-1 and NQO1 in ALI mice. In vitro, SA obviously repressed the expressions of inflammatory cytokines and the JNK/p38-NF-κB/AP-1 pathway. SA also regulated the expression of oxidative stress-related genes through the Nrf2 pathway. Taken together, SA exhibits a protective role by modulating the anti-inflammatory and anti-oxidation pathways in ALI, and it may be a promising candidate for functional foods to prevent ALI. [ABSTRACT FROM AUTHOR]

Background: Cognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients. Methods: In this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients' cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients' depressive symptoms at baseline and week 2. Results: After 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p < 0.05). Moreover, post hoc tests revealed a significant increase in the RBANS total score and Visuospatial/Constructional in the combined treatment group compared to the other three groups but in the immediate memory, the combined treatment group only showed a better improvement than the sham group. The results also showed the RBANS total score increased significantly higher in the active rTMS group compared with the sham group. However, rTMS or tDCS alone was not superior to the sham group in terms of other cognitive performance. In addition, the rTMS combined with the tDCS group showed a greater reduction in HDRS-24 total score and a better depression response rate than the other three groups. Conclusions: rTMS combined with tDCS treatment is more effective than any single intervention in treating cognitive dysfunction and depressive symptoms in MDD patients. Trial registration: Chinese Clinical Trial Registry (ChiCTR2100052122). [ABSTRACT FROM AUTHOR]

A K2CO3 promoted spirocyclopropanation of thiazole‐derived oxadienes with bromomalonate via 1, 4‐addition‐induced dearomatization strategy has been developed. The pathway features a broad substrate scope, operational simplicity and high degree of synthetic efficiency to afford series of functionalized spiro‐cyclopropanation frameworks in 88 %–96 % yields, which enriches the research contents of thiazole‐derived oxadienes involved reactions. All products obtained herein contain two contiguous quaternary centers and their further synthetic applications are also demonstrated. [ABSTRACT FROM AUTHOR]