Isolation, Purification, and Structural Characterization of Polysaccharides from Codonopsis pilosula and Their Anti-Tumor Bioactivity by Immunomodulation.

The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (<60 wDa), CPPS-II (60-100 wDa), and CPPS-III (>100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT-IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 µg/mL) group at 125 µg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

Rhodiola rosea polysaccharides-based nanoparticles loaded with DOX boosts chemo-immunotherapy for triple-negative breast cancer by re-educating Tumor-associated macrophages.

Hydrophobic drug delivery vectors suffer significant challenges in cancer therapy, including efficient encapsulation and tumor targeting ability. In the present study, Rhodiola rosea polysaccharides (RHPs), which have the ability to modulate Tumor-associated macrophages and typical structural characteristics, were employed as an immunoactive vector for drug delivery. Folic acid (FA) and stearic acid (SA) were chemically modified to the backbone of RHPs to obtain the self-assembly and tumor-targeting behavior. Further, the hydrophobic drug, doxorubicin (DOX), was encapsulated in the RHPs derivatives (FA-RHPs-SA) with high efficiency. Additionally, the optimally formed DOX@FA-RHPs-SA had a uniform size distribution of approximately 196 nm and a pH-sensitive release capacity in different acidic conditions. In vitro experiments demonstrated that tumor cells could efficiently uptake DOX@FA-RHPs-SA. Furthermore, the modulatory function of the FA-RHPs-SA on RAW264.7 macrophages was also demonstrated in the transition from M0 to M1 phenotypes, and the M2 differentiated into the M1. Finally, the in vivo antitumor study revealed that the inhibitory effect of DOX@FA-RHPs-SA was superior to the DOX monotherapy treatment, and the new preparation functioned synergistically by inducing tumor cell apoptosis and modulating immune cell function. In conclusion, this study described an RHPs-based hydrophobic delivery vector and achieved an additional helpful antitumor effect by modulating Tumor-associated macrophages.

Biological denitrification in a macrophytic lake: implications for macrophytes-dominated lake management in the north of China.

Denitrification plays an important role in nitrogen (N) removal in freshwater ecosystems. Aquatic plants might have an impact on the sediment denitrification of water body, especially in macrophytes-dominated lake; however, there were different opinions about it. Our hypothesis was that the sediment denitrification rates differ significantly in different vegetation zones and seasons because of direct and indirect effect of the aquatic plants. Therefore, we studied sediment denitrification in Dongping Lake, a typical macrophytes-dominated lake located in the north of China. The acetylene inhibition technique was used to quantify the sediment denitrification rates (DRs) in the Phragmites communis (P. communis) zone, aquaculture zone, Potamogeton crispus (P. crispus) zone and mixed vegetation zone in July (summer), October (autumn), December (winter) of 2015 and March (spring) of 2016. The results showed that the average DRs were significantly higher in the P. communis zone (69.0 ± 91.6 µmol N m-2 h-1) than the mixed vegetation zone (8.70 ± 5.44 µmol N m-2 h-1), and the average DRs represented significant seasonal difference as in the order of winter (74.5 ± 88.3 µmol N m-2 h-1) > autumn (15.7 ± 18.6 µmol N m-2 h-1) ≈ summer (10.7 ± 5.90 µmol N m-2 h-1) > spring (3.85 ± 1.29 µmol N m-2 h-1). The DRs generally decreased with the increasing of depth; however, significant increase of DRs with depth were found in certain seasons at the vegetated zones except the non-vegetated zone (the aquaculture zone) indicating the possible rhizosphere effect of aquatic plants on denitrification. The higher DRs and cycling rates of nitrate in the P. communis zone might be related to the larger biomass and oxygen transporting capacity of P. communis than those of the other aquatic plants. Winter peaks of DRs might be attributed to the higher NO3- load and the absence of the plant uptake. The high cycling rates of nitrate in Dongping Lake indicated an enhanced internal N cycling by aquatic plants. Sediment denitrification could remove about 537.7 t N every year, which was about 26.5% of annual TN loading in Dongping Lake.