Dual-Fuel Propelled Nanomotors with Two-Stage Permeation for Deep Bacterial Infection in the Treatment of Pulpitis.

Bacterial infection-induced inflammatory response could cause irreversible death of pulp tissue in the absence of timely and effective therapy. Given that, the narrow structure of root canal limits the therapeutic effects of passive diffusion-drugs, considerable attention has been drawn to the development of nanomotors, which have high tissue penetration abilities but generally face the problem of insufficient fuel concentration. To address this drawback, dual-fuel propelled nanomotors (DPNMs) by encapsulating L-arginine (L-Arg), calcium peroxide (CaO2 ) in metal-organic framework is developed. Under pathological environment, L-Arg could release nitric oxide (NO) by reacting with reactive oxygen species (ROS) to provide the driving force for movement. Remarkably, the depleted ROS could be supplemented through the reaction between CaO2 with acids abundant in the inflammatory microenvironment. Owing to high diffusivity, NO achieves further tissue penetration based on the first-stage propulsion of nanomotors, thereby removing deep-seated bacterial infection. Results indicate that the nanomotors effectively eliminate bacterial infection based on antibacterial activity of NO, thereby blocking inflammatory response and oxidative damage, forming reparative dentine layer to avoid further exposure and infection. Thus, this work provides a propagable strategy to overcome fuel shortage and facilitates the therapy of deep lesions.

Optimization of Three Extraction Methods and Their Effect on the Structure and Antioxidant Activity of Polysaccharides in Dendrobium huoshanense.

Dendrobium huoshanense is a famous edible and medicinal herb, and polysaccharides are the main bioactive component in it. In this study, response surface methodology (RSM) combined with a Box-Behnken design (BBD) was used to optimize the enzyme-assisted extraction (EAE), ultrasound-microwave-assisted extraction (UMAE), and hot water extraction (HWE) conditions and obtain the polysaccharides named DHP-E, DHP-UM, and DHP-H. The effects of different extraction methods on the physicochemical properties, structure characteristics, and bioactivity of polysaccharides were compared. The differential thermogravimetric curves indicated that DHP-E showed a broader temperature range during thermal degradation compared with DHP-UM and DHP-H. The SEM results showed that DHP-E displayed an irregular granular structure, but DHP-UM and DHP-H were sponge-like. The results of absolute molecular weight indicated that polysaccharides with higher molecular weight detected in DHP-H and DHP-UM did not appear in DHP-E due to enzymatic degradation. The monosaccharide composition showed that DHPs were all composed of Man, Glc, and Gal but with different proportions. Finally, the glycosidic bond types, which have a significant effect on bioactivity, were decoded with methylation analysis. The results showed that DHPs contained four glycosidic bond types, including Glcp-(1→, →4)-Manp-(1→, →4)-Glcp-(1→, and →4,6)-Manp-(1→ with different ratios. Furthermore, DHP-E exhibited better DPPH and ABTS radical scavenging activities. These findings could provide scientific foundations for selecting appropriate extraction methods to obtain desired bioactivities for applications in the pharmaceutical and functional food industries.

Component identification of modified sanmiao pills by UPLC-Xevo G2-XS QTOF and its anti-gouty arthritis mechanism based on network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified sanmiao pills (MSMP), a traditional Chinese medicine (TCM) formula, is consisted of rhizome of Smilax glabra Roxb., Cortexes of Phellodendron chinensis Schneid., rhizome of Atractylodes chinensis (DC.) Koidz., and roots of Cyathula officinalis Kuan. in a ratio of 3:3:2:1. This formula has been broadly applied to treat gouty arthritis (GA) in China. AIMS OF THE STUDY: To elaborate the pharmacodynamic material basis and pharmacological mechanism of MSMP against GA. MATERIALS AND METHODS: UPLC-Xevo G2-XS QTOF combined with UNIFI platform was applied to qualitatively assess the chemical compounds of MSMP. Network pharmacology and molecular docking were used to identify the active compounds, core targets and key pathways of MSMP against GA. The GA mice model was established by MSU suspension injecting into ankle joint. The swelling index of ankle joint, expressions of inflammatory cytokines, and histopathological changes in mice ankle joints were determined to validate the therapeutic effect of MSMP against GA. The protein expressions of TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome in vivo was detected by Western blotting. RESULTS: In total, 34 chemical compounds and 302 potential targets of MSMP were ascertained, of which 28 were overlapping targets pertaining to GA. 143 KEGG enrichment pathway were obtained, of which the NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, and NF-κB signaling pathway were strongly associated with GA. In silico study indicated that the active compounds had excellent binding affinity to core targets. In vivo study confirmed that MSMP observably decreased swelling index and alleviated pathological damage to ankle joints in acute GA mice. Besides, MSMP significantly inhibited the secretion of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) induced by MSU, as well as the expression levels of key proteins involved in TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome. CONCLUSION: MSMP possessed a pronounced therapeutic effect on acute GA. Results from network pharmacology and molecular docking showed that obaculactone, oxyberberine, and neoisoastilbin might treat gouty arthritis by down-regulating TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome.