5-Demethylnobiletin and its major metabolites:efficient preparation and mechanism of their anti-proliferation activity in HepG2 cells

5-Demethylnobile tin(5-DMN),a hydroxylated polymethoxyflavone(OH-PMF)identified in aged citrus peels,has demonstrated health benefiting effects in previous studies.5-DMN undergoes biotransformation in vivo,yielding 5,3’-didemethylnobiletin(5,3’-DDMN),5,4’-didemethylnobiletin(5,4’-DDMN)and5,3’,4’-tridemethylnobiletin(5,3’,4’-TDMN).However,the anti-cancer effects of 5-DMN and its in vivo metabolites against HepG2 cells remain unclear.In this study,an efficient chemical synthetic method was developed to obtain 5-DMN and its 3 metabolites,and their molecular structures were confirmed by;H NMR and LC-MS.Cytotoxicity,cell cycle arrestment,apoptosis and caspase-3 expression were investigated to evaluate the anti-liver cancer effects of these OH-PMFs on HepG2 cells.The results showed that all 4 compounds inhibited the proliferation of HepG2 cells in a concentration-dependent manner.Their anti-proliferative activity was exerted through inducing G2/M phase arrestment,cell apoptosis and promoting expression of a key apoptotic protein called cleaved caspase-3.Our results indicated that 5,3’-DDMN and5,3’,4’-TDMN showed a stronger inhibitory activity on cell proliferation than 5-DMN,followed by 5,4’-DDMN.The expression of cleaved caspase-3 was the highest in cells treated with 5,4’-DDMN,implying that the apoptosis induced by other OH-PMFs might be mediated by other apoptotic execution proteins.Our research reveals the application potential and scientific evidence for the production and functionality of OH-PMFs.

Antimony removal from wastewater by sulfate-reducing bacteria in a bench-scale upflow anaerobic packed-bed reactor

The objective of this research was to study the precipitation of Sb and the stability of Sb2S3 during treatment of synthetic Sb(V)wastewater by sulfate-reducing bacteria(SRB).We investigated the transformation and precipitation of Sb,as well as the re-dissolution of Sb2S3 under different pH and carbon sources.The results showed that the precipitation of aqueous Sb and the re-dissolution of Sb2S3 depend on the conversion between Sb(Ⅲ)-S(-Ⅱ)complexes and Sb2S3 precipitates.These processes were highly pH-dependent,and a decrease in pH enhanced reduction of Sb(Ⅴ)and precipitation of Sb2S3 were observed.The newly formed Sb2S3 was found to be unstable and could re-dissolve through complexation with H2 S due to the increase in pH.When pH decreased to approximately 6.5,Sb was almost completely transformed into Sb2S3 precipitates,and the Sb2S3 precipitates were relatively stable.Compared with lactate as a carbon source,ethanol resulted in a comparable H2 S yield and a relatively low pH and was,therefore,more conducive to the removal of Sb(Ⅴ).The results of this study suggest that when removing Sb(Ⅴ)in wastewater by SRB,it is important to control the pH at a relatively low level.

Tea and Citrus maxima complex induces apoptosis of human liver cancer cells via PI3K/AKT/mTOR pathway in vitro

Objective:In this study,black tea and Citrus maxima(BT-CM),yellow tea and C.maxima(YT-CM),green tea and C.maxima(GT-CM)as subjects,the active ingredient content and antioxidant activity of three tea and C.maxima(T-CM)were analyzed.The effects of three T-CMs on apoptosis of liver cells in vitro and its mechanism were further explored.Methods:National standard method and HPLC were used for active ingredient analysis.MTT,cell fow cytometry and Western blot were used to analyze the effects of three T-CMs on cell proliferation,apoptosis,and its underlying molecular mechanism.Results:The content of tea polyphenols,free amino acids,ratio of polyphenols and amino acids,ester catechins,non-ester catechins and caffeine in YT-CM and GT-CM was significantly higher than that of BT-CM.The in vitro antioxidant capacity of YT-CM and GT-CM was also significantly stronger than that of BT-CM.Three T-CMs had the effects of inhibiting proliferation,arresting cell cycle and inducing apoptosis in HepG2 and Bel7402 cells,especially YT-CM and GT-CM.Western blot analysis showed three T-CMs activated PI3K/AKT/mTOR signaling pathway and regulated the expression levels of apoptosis-related proteins Bax,Bcl-2 and Caspase-3/9.YT-CM and GT-CM had better ability to change the signal pathway than BT-CM.Conclusion:In short,T-CMs,which combined different degrees of fermentation tea with C.maxima,were rich in nutrients and biologically active substances.T-CMs,especially YT-CM and GT-CM,are healthy drinks that help to prevent and treat liver cancer.

Observability Inequality for the Kirchhoff-Rayleigh Plate Like Equation in a Short Time

In this paper, for any given observation time and suitable moving observation domains, the author establishes a sharp observability inequality for the Kirchhoff-Rayleigh plate like equation with a suitable potential in any space dimension. The approach is based on a delicate energy estimate. Moreover, the observability constant is estimated by means of an explicit function of the norm of the coefficient involved in the equation.

Hawanoids A–E, unprecedented diterpenoids with PAF-induced platelet aggregation inhibitory activities from the deep-sea-derived fungus Paraconiothyrium hawaiiense

Hawanoids A–E(1–5), five highly cyclized diterpenoids were isolated from the deep-sea-derived fungus Paraconiothyrium hawaiiense FS482. Compounds 1 and 2 possessed an unprecedented tetracyclo[6.6.2.0^(2,7).0^(11,15)]cetane carbon skeleton while 3 and 4 possessed an unusual 11,14-macrocyclic ether moiety in phomactin family. Their structures including the stereo-chemistry were determined through spectroscopic analysis, X-ray diffractions and computational calculations. The plausible biosynthetic pathway was proposed based on the predicted biosynthetic gene cluster. All of the isolated compounds exhibited inhibitory activities against PAF-induced platelet aggregation. The molecular docking study was carried out understand the interaction between the PAF receptor and hawanoids with different skeletons.