Multifunctional Hybrid Hydrogel Enhanced Antitumor Therapy through Multiple Destroying DNA Functions by a Triple-Combination Synergistic Therapy.

Brachytherapy, as an effective setting for precise cancer therapy in clinic, can lead to serious DNA damage. However, its therapeutic efficacy is always limited by the DNA self-repair property, tumor hypoxia-associated radiation resistance as well as inhomogeneous distribution of the radioactive material. Herein, a multifunctional hybrid hydrogel (131 I-hydrogel/DOX/GNPs aggregates) is developed by loading gold nanoparticle aggregates (GNPs aggregates) and DOX into a radionuclide iodine-131 (131 I) labelled polymeric hydrogels (131 I-PEG-P(Tyr)8 ) for tumor destruction by completely damaging DNA self-repair functions. This hybrid hydrogel exhibits excellent photothermal/radiolabel stability, biocompatibility, and fluorescence/photothermal /SPECT imaging properties. After local injection, the sustained releasing DOX within tumor greatly inhibits the DNA replication. Meanwhile, GNPs aggregates as a radiosensitizer and photosensitizer show a significant improvement of brachytherapeutic efficacy and cause serious DNA damage. Simultaneously, GNPs aggregates induce mild photothermal therapy under 808 nm laser irradiation, which not only inhibits self-repair of the damaged DNA but also effectively relieves tumor hypoxic condition to enhance the therapeutic effects of brachytherapy, leading to a triple-synergistic destruction of DNA functions. Therefore, this study provides a highly efficient tumor synergistic therapy platform and insight into the synergistic antitumor mechanism in DNA level.

Abscisic acid suppresses the activation of NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation.

Abscisic acid (ABA), a well-known natural phytohormone reportedly exerts anti-inflammatory and anti-oxidative properties in diabetes and colitis. However, the efficacy of ABA against allergic airway inflammation and the underlying mechanism remain unknown. Herein, an OVA-induced murine allergic airway inflammation model was established and treated with ABA in the presence or absence of PPAR-γ antagonist GW9662. The results showed that ABA effectively stunted the development of airway inflammation, and concordantly downregulated OVA-induced activation of NLRP3 inflammasome, suppressed oxidative stress and decreased the expression of mitochondrial fusion/fission markers including Optic Atrophy 1 (OPA1), Mitofusion 2 (Mfn2), dynamin-related protein 1 (DRP1) and Fission 1 (Fis1). Moreover, ABA treatment further increased OVA-induced expression of PPAR-γ, while GW9662 abrogated the inhibitory effect of ABA on allergic airway inflammation as well as on the activation of NLRP3 inflammasome and oxidative stress. Consistently, ABA inhibited the activation of NLRP3 inflammasome, suppressed oxidative stress and mitochondrial fusion/fission in LPS-stimulated Raw264.7 cells via PPAR-γ. Collectively, ABA ameliorates OVA-induced allergic airway inflammation in a PPAR-γ dependent manner, and such effect of ABA may be associated with its inhibitory effect on NLRP3 inflammasome and oxidative stress. Our results suggest the potential of ABA or ABA-rich food in protecting against asthma.

Impact of poplar-based phytomanagement on metal bioavailability in low-phosphorus calcareous soil with multi-metal contamination.

Bioavailability of trace metals (TMs) is the key component in the management of TM-contaminated soils; however, its impact mechanism is unclear in low-phosphorus (P) calcareous soils afforested by fast-growing tree species for a long duration (>10 years). We selected a site contaminated with multiple TMs and phytomanaged by poplar (Populus hopeiensis Hu & Chow) to study the impact mechanism of plant-soil interactions on TM bioavailability along a long-term chronosequence (i.e., 10, 15, 20, and 25 years). We found that phytomanagement significantly decreased soil organic carbon (SOC) content, soil total nitrogen (N) content, and soil C/P and N/P ratios with stand age, but did not significantly change soil total P content. In contrast, soil available P content significantly changed in rhizospheric soils compared with the bulk soil, suggesting the tight coupling between the amplification of P turnover and N availability. Soil pH in rhizospheric soils significantly decreased by 0.22 to 0.32 units, while calcium carbonate (CaCO3) content decreased by 14% to 39%, as compared with the bulk soil. Bioavailable concentrations of cadmium, lead, and zinc were positively correlated with soil available P, whereas bioavailable nickel concentration was negatively correlated with soil pH. Furthermore, TM bioavailability in rhizospheric soils significantly increased with stand age, regardless of the metal type. Our results suggest that P mobilization associated with SOC depletion induced soil acidification followed by CaCO3 dissolution, collectively leading to metal mobilization with stand age.