Pectin-based double network hydrogels as local depots of celastrol for enhanced antitumor therapy.

In this study, A double-network (DN) hydrogel composed of a physical glycyrrhizic acid (GA) network and a chemically crosslinked pectin-based network was fabricated as a local depot of celastrol (CEL) for cancer treatment. The obtained DN hydrogel possessed excellent mechanical performance, flexibility, biocompatibility, biodegradability and self-healing property. Furthermore, the release profile of CEL loaded DN hydrogel maintained a controlled and sustained release of CEL for a prolonged period. Finally, in vivo animal experiments demonstrated that the DN hydrogel could significantly enhance the therapeutic efficiency of CEL in CT-26 tumor-bearing mice upon intratumoral injection while effectively alleviate the toxicity of the CEL. In summary, this injectable pectin-based double network hydrogels are ideal delivery vehicle for tumor therapy.

Mechanism of YY1 mediating autophagy dependent ferroptosis in PM2.5 induced cardiac fibrosis.

Epidemiological studies have demonstrated strong associations between exposure to ambient fine particulate matter (PM2.5) and cardiac disease. To investigate the potential mechanism of cardiac fibrosis induced by PM2.5, we established PM2.5 exposure models in vivo and in vitro, and then cardiac fibrosis was evaluated. The ferroptosis and ferritinophagy was detected to characterize the effects of PM2.5 exposure. The results indicated that PM2.5 exposure could induce cardiac fibrosis in mice. YY1 was induced by PM2.5 exposure and then increased NCOA4, a cargo receptor for ferritinophagy, which interacted with FHC and promoted the transport of ferritin to the autophagosome for degradation. The release of large amounts of free iron from ferritinophagy led to lipid peroxidation directly via the Fenton reaction, thereby triggering ferroptosis. Moreover, siNCOA4 could partly restore the FHC protein level in HL-1 cells and inhibit the occurrence of downstream ferroptosis. Functionally, NCOA4 knockdown inhibited ferroptosis and alleviated HL-1 cell death induced by PM2.5. Ferroptosis inhibitor (Ferrostatin-1) could reverse the promoting effect of ferritinophagy mediated ferroptosis on cardiac fibrosis induced by PM2.5 exposure in mice. Our study indicated that PM2.5 induced cardiac fibrosis through YY1 regulating ferritinophagy-dependent ferroptosis.

Revealment study on the regulation of lipid metabolism by Lingguizhugan Decoction in heart failure treatment based on integrated lipidomics and proteomics.

Lingguizhugan Decoction (LGZGD) is a classical traditional Chinese medicine prescription. Our previous studies found that disorders of lipid metabolism were reversed by LGZGD in heart failure (HF) mice. This study aimed to reveal the regulation of lipid metabolism of LGZGD. A mice model of HF was established by intraperitoneal injection of doxorubicin. The components of LGZGD were identified with the UHPLC-QTOF-MS method. The regulation of lipid metabolism by LGZGD was detected by serum lipidomics and heart tissue proteomics. Molecular docking was further performed to screen active components. A total of 78 compounds in LGZGD were identified. Results of lipidomics showed that 37 lipids illustrated a significant recovery trend to normal after the treatment of LGZGD. Results of proteomics demonstrated that 55 proteins were altered by the administration of LGZGD in HF mice. After enrichment analysis, the Prakg2/Ucp2/Plin1 axis on the Apelin pathway plays a vital role in HF treatment by LGZGD. Nine active components exhibited the outstanding ability of binding to the apelin receptor with MM-GBSA value lower than -60 Kcal/mol. In conclusion, all results combined together revealed that multi-component in the LGZGD had beneficial effects on the HF through ameliorating lipid disorders, which provides a novel insight into the cardioprotective effects of LGZGD and its clinical application.

Synchronous Investigation of the Mechanism and Substance Basis of Tripterygium Glycosides Tablets on Anti-rheumatoid Arthritis and Hepatotoxicity.

Tripterygium Glycosides Tablets (TGT) has shown obvious anti-rheumatoid arthritis (RA) effects accompanied by hepatotoxicity. Despite that many studies looked at TGT's anti-RA or hepatotoxic mechanism and substance basis, the results were still insufficient. Furthermore, the anti-RA and hepatotoxicity investigations of TGT were undertaken separately, neglecting the relationship between efficacy and toxicity. Herein, an integrated approach combining metabolomics, network pharmacology, serum pharmacochemistry, and molecular docking was adopted to elucidate the mechanism and substance basis of Tripterygium Glycosides Tablets (TGT) on anti-rheumatoid arthritis and hepatotoxicity simultaneously. The results showed that 33 components in TGT were absorbed into rat serum. Two toxic targets (PRKCA, FASN), three effective targets (PLA2G10, PTGES, PLA2G1B), and four effective and toxic targets (PTGS1, PTGS2, PLA2G2A, ALOX5) were obtained by metabolomics combined with network analysis and network pharmacology. A component-target-RA-hepatotoxicity network was constructed and five hepatotoxic components (1-desacetylwilforgine, wilfordconine, wilforgine, wilformine, wilfornine D), eight effective-toxic components (14-oxo-19-(4 → 3) abeo-abieta-3,8,12-tetraen-19,18-olide, 7-oxo-18(4 → 3) abeo-abieta-3,8,11,13-tetraen-18-oic acid, hypoglaulide, triptotriterpenic acid A, wilforol F, wilforlide B, triptoquinone B, wilforlide A); and 23 non-effective and non-toxic components were acquired and validated by molecular docking. In addition, our research revealed that glycerophospholipid metabolism and ether lipid metabolism were correlated to both hepatotoxicity and anti-RA of TGT. While in sphingolipid metabolism, ceramidases regulated ceramide-sphingosine and phytoceramide-phytosphingosine reaction were found to be correlated to hepatotoxicity, sphinganine-1-phosphate lyase (SPL) regulated sphingosine 1-phosphate (S1P)-phosphoethanolamine and sphinganine 1-phosphate-phosphoethanolamine were found to be attributed to anti-RA effects.

[Impact of pH on the generation of COD, phosphorous and ammonia-nitrogen during the anaerobic fermentation of excess activated sludge].

There are mainly two kinds of sludge in the municipal wastewater treatment plant, i. e. , primary and secondary sludge. This study investigated the effect of pH, ranging from 4.0-11.0, on hydrolysis in terms of soluble chemical oxygen demand (SCOD) production in the anaerobic solubilization of excess activated sludge at 20-22 degrees C. It was found that when the value of pH was 8.0-10.0, the production quantity of SCOD were higher than pH = 5.0-7.0. Especially when the pH was 10.0 or 11.0, the value of SCOD was almost 10 times of pH = 6.0 during the whole fermentation of 20 days. And volatile fatty acids (VFA) production on the 8th day under alkaline condition was higher than that under acidic condition.