Isorhamnetin Suppresses Human Gastric Cancer Cell Proliferation through Mitochondria-Dependent Apoptosis.

Derivates of natural products have been wildly utilized in the treatment of malignant tumors. Isorhamnetin (ISO), a most important active ingredient derived from flavonoids, shows great potential in tumor therapy. However, the therapeutic effects of ISO on gastric cancer (GC) remain unclear. Here, we demonstrate that ISO treatment dramatically inhibited the proliferation of two types of GC cells (AGS-1 and HGC-27) both in vitro and in vivo in time- and dose-dependent manners. These results are consistent with the transcriptomic analysis of ISO-treated GC cells, which yielded hundreds of differentially expressed genes that were enriched with cell growth and apoptosis. Mechanically, ISO treatment initiated the activation of caspase-3 cascade and elevated the expression of mitochondria-associated Bax/Bcl-2, cytosolic cytochrome c, followed by the activation of the cleavage of caspase-3 as well as poly ADP-ribose polymerase (PARP), resulting in the severe reduction of the mitochondrial potential and the accumulation of reactive oxygen species (ROS), while pre-treatment of the caspase-3 inhibitor could block the anti-tumor effect. Therefore, these results indicate that ISO treatment induces the apoptosis of GC cells through the mitochondria-dependent apoptotic pathway, providing a potential strategy for clinical GC therapy.

The responses of photosystem II and intracellular ATP production of Arabidopsis leaves to salt stress are affected by extracellular ATP.

Hypertonic salt stress with different concentrations of NaCl increased the levels of extracellular ATP of Arabidopsis leaves. And, hypertonic salt stress decreased the levels of F v /F m (the maximal efficiency of photosystem II), Φ PSII (the photosystem II operating efficiency), qP (photochemical quenching), and intracellular ATP (iATP) production. The treatment with ß,γ-methyleneadenosine 5'-triphosphate (AMP-PCP), which can exclude extracellular ATP from its binding sites of extracellular ATP receptors, caused a further decrease in the levels of F v /F m , Φ PSII, qP, and iATP production of the salt-stressed Arabidopsis leaves, while the addition of exogenous ATP rescued the inhibitory effects of AMP-PCP on Φ PSII , qP, and iATP production under hypertonic salt stress. Under hypertonic salt stress, the values of F v /F m , Φ PSII , qP, and iATP production were lower in the dorn 1-3 mutant than in the wild-type plants. These results indicate that the responses of photosystem II and intracellular ATP production to salt stress could be affected by extracellular ATP.

H2S scavenger as a broad-spectrum strategy to deplete bacteria-derived H2S for antibacterial sensitization.

Bacteria-derived H2S plays multifunctional protective roles against antibiotics insult, and the H2S biogenesis pathway is emerging as a viable target for the antibacterial adjuvant design. However, the development of a pan-inhibitor against H2S-synthesizing enzymes is challenging and underdeveloped. Herein, we propose an alternative strategy to downregulate the H2S levels in H2S-producing bacteria, which depletes the bacteria-derived H2S chemically by H2S scavengers without acting on the synthesizing enzymes. After the screening of chemically diversified scaffolds and a structural optimization campaign, a potent and specific H2S scavenger is successfully identified, which displays efficient H2S depletion in several H2S-producing bacteria, potentiates both bactericidal agents and photodynamic therapy, enhances the bacterial clearance of macrophages and polymorphonuclear neutrophils, disrupts the formation of bacterial biofilm and increases the sensitivity of bacterial persister cells to antibiotics. Most importantly, such an H2S scavenger exhibits sensitizing effects with gentamicin in Pseudomonas aeruginosa -infected pneumonia and skin wound female mouse models. In aggregate, our results not only provide an effective strategy to deplete bacteria-derived H2S and establish the H2S biogenesis pathway as a viable target for persisters and drug-resistant bacteria, but also deliver a promising antibacterial adjuvant for potential clinical translation.

Mechanistic insights into pH-dependent H2 photoproduction in bisulfite-treated Chlamydomonas cells.

BACKGROUND: Bisulfite addition is an important H2 photoproduction strategy that removes O2 and activates hydrogenase. The pH values of cell cultures can change the ratio of bisulfite to sulfite, which may affect H2 photoproduction. However, little is known regarding the pH effect of bisulfite addition on H2 photoproduction and relevant underlying mechanism. RESULTS: Here, changes in H2 photoproduction with different initial extracellular pH values showed a parabolic distribution and a pH of 8.0 is an optimal value for H2 photoproduction in Chlamydomonas reinhardtii cells treated with bisulfite. Compared to the growth pH (pH 7.3), increased photoproduction of H2 at this optimal pH was primarily caused by a relatively high residual activity of photosystem II (PSII), which provides a relatively plentiful source of electrons for H2 photoproduction. Such increased H2 photoproduction was most likely a result of decreased the ratio of bisulfite to sulfite, consistent with the result that the toxicity of bisulfite on PSII was much more than that of sulfite. This possibility was corroborated by the result that treatment with a combination of 7 mM bisulfite and 6 mM sulfite further enhanced H2 photoproduction compared with 13 mM bisulfite alone. CONCLUSIONS: Collectively, our findings provide novel mechanistic insights into pH-dependent H2 photoproduction in C. reinhardtii cells treated with bisulfite, and demonstrate that sulfite addition is another important strategy for H2 photoproduction, just like bisulfite addition.

A Stepwise NaHSO3 Addition Mode Greatly Improves H2 Photoproduction in Chlamydomonas reinhardtii.

NaHSO3 addition greatly increases the yield of H2 photoproduction in a unicellular green alga Chlamydomonas reinhardtii through removing O2 and activating hydrogenase but significantly impairs the activity of PSII, an electron source for H2 photoproduction. Here, a stepwise addition mode of total 13 mM NaHSO3, an optimal concentration for H2 photoproduction of C. reinhardtii identified in a previous one step addition method, significantly improved H2 photoproduction. Such improvement was believed to be the result of increased residual PSII activity in an anaerobic background, but was at least independent of two alternative electron sinks for H2 photoproduction, cyclic electron transport around PSI and CO2 assimilation. Based on the above results, we propose that increased residual PSII activity in an anaerobic environment is an efficient strategy to enhance H2 photoproduction in C. reinhardtii, and the stepwise NaHSO3 addition mode is a case study in the strategy.

Synthesis of mesoporous silica by a surface charge reversal route.

Pore size adjustable mesoporous silica was synthesized by adsorption of varying amounts of sodium dodecyl benzenesulfonate at the surface of silica activated by zinc ion via a novel surface charge reversal route. The pore size and volume can be adjusted from 5.9 to 13.76 nm and 0.88 to 1.08 cm(3) g(-1), respectively, with increasing the SDBS concentration from 0.77 to 3.08 mmol L(-1). Adsorption of Zn(2+) as a function of pH and N(2) adsorption/desorption isotherms demonstrated that the metal ions such as Zn(2+) could be readily removed with dilute nitric acid without apparent collapse of the pore structure at the proper range of SDBS concentration.