Docosahexaenoic Acid-Enriched Phosphatidylcholine Exerted Superior Effects to Triglyceride in Ameliorating Obesity-Induced Osteoporosis through Up-Regulating the Wnt/β-Catenin Pathway

Article

作者: Wang, Jingfeng ; Dong, Ping ; Bo, Yuying ; Tian, Yingying ; Xue, Changhu ; Yue, Hao ; Mao, Lei

A growing number of studies reported that obesity is one of the major inducements for osteoporosis by promoting excessive adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Marine-derived DHA-enriched phosphatidylcholine (DHA-PC) exhibited activities to improve ovariectomized-induced osteoporosis and kidney damage. However, the potential effect of DHA-PC and efficacy differences between DHA-PC and traditional DHA (DHA-triglyceride, DHA-TG) on BMSCs differentiation in obesity-induced osteoporosis were not clear. In the present study, obesity-induced osteoporotic mice were supplemented with DHA-TG and DHA-PC for 120 days. Results showed that supplementing with DHA-PC improved the bone mineral density and biomechanical properties, increased the new bone formation rate by 55.2%, and reduced the amount of bone marrow fat to a greater extent than DHA-TG. Further in vitro results showed that DHA-PC significantly promoted the osteogenic differentiation and inhibited the adipogenic differentiation of BMSCs. Mechanistically, DHA-PC supplement up-regulated Wnt/β-catenin pathway in BMSCs and up-regulated the expression of osteogenic transcription factors, thereby promoting osteogenic differentiation. In summary, DHA-PC exerted a superior effect to DHA-TG in improving obesity-induced osteoporosis. The results provided new evidence for the application of different molecular forms of DHA in treatment of osteoporosis.

2022-01-01·Biomaterials1区 · 工程技术

Co-delivery of dihydroartemisinin and pyropheophorbide-iron elicits ferroptosis to potentiate cancer immunotherapy

1区 · 工程技术

Article

作者: Li, Youyou ; Lin, Wenbin ; Chan, Christina ; Duan, Xiaopin ; Ni, Kaiyuan ; Han, Wenbo

Dihydroartemisinin (DHA) has shown cytotoxicity against various tumor cells in vitro in an iron-dependent manner, but its in vivo antitumor efficacy is compromised by its rapid degradation and clearance. Here we show the induction of ferroptosis by DHA in an immunogenic fashion and the maximization of in vivo antitumor efficacy of DHA by co-delivering a cholesterol derivative of DHA (Chol-DHA) and Pyropheophorbide-iron (Pyro-Fe) in ZnP@DHA/Pyro-Fe core-shell nanoparticles. ZnP@DHA/Pyro-Fe particles stabilize DHA against hydrolysis and prolong blood circulation of Chol-DHA and Pyro-Fe for their enhanced uptake in tumors. Co-delivery of an exogenous iron complex and DHA induces more ROS production and causes significant tumor inhibition in vivo. By increasing tumor immunogenicity, the combination of DHA and Pyro-Fe sensitizes non-immunogenic colorectal tumors to anti-PD-L1 checkpoint blockade immunotherapy. These findings suggest the potential of using nanotechnology to repurpose DHA and other drugs with excellent safety profiles for combination with immune checkpoint blockade to treat cancers.

2020-03-01·Doklady Biochemistry and Biophysics4区 · 生物学

Neuroprotective and Antioxidant Activity of Arachidonoyl Choline, Its Bis-Quaternized Analogues and Other Acylcholines

4区 · 生物学

Article

作者: Makhaeva, G F ; Bosaya, A A ; Rudakova, E V ; Tsetlin, V I ; Kagarlitsky, G O ; Bezuglov, V V ; Fomina-Ageeva, E V ; Akimov, M G ; Eremin, S A ; Gretskaya, N M ; Dudina, P V

The antioxidant activity and protective effect in the toxicity model of H₂O₂ were studied for arachidonic (AA-CHOL), docosahexaenoic (DHA-CHOL), linoleic (Ln-CHOL), and oleic (Ol-CHOL) fatty acids, as well as arachidonoyl dicholine (AA-diCHOL) and O-arachidonoyl bistetramethylaminoisopropanol (ABTAP). AA-CHOL, DHA-CHOL and Ln-CHOL provided a 20% increase in cell survival. AA-CHOL, AA-diCHOL, Ol-CHOL, and ABTAP had a radical-scavenging effect in the ABTS test, approximately equal to the activity of a standard radical scavenger Trolox.

100 项与 TP-352 相关的药物交易

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