The Inhibitory Effect of Oridonin on the Growth of Fifteen Human Cancer Cell Lines

OBJECTIVE To study the inhibitory effect of oridonin on the growth of cancer cells. METHODS Fifteen human cancer cell lines were subjected to various concentrations of oridonin in culture medium. The inhibitory rate of cell growth was measured by the MTT assay, and compared with a negative control and 5-Fu-positive control. RESULTS The 50% inhibiting concentration （IC50） and maximal inhibition （Imax） of oridonin shown by studying the growth of the cancer cell lines were as follows： leukemias （HL60 cells： 3.9 μg/ml and 73.8%, K562 cells： 4.3 μg/ml and 76.2%）; esophageal cancers（SHEEC cells： 15.4 μg/ml and 99.2%, Eca109 cells： 15.1 μg/ml and 84.6%, TEl cells： 4.0 μg/ml and 70.2%）; gastric cancers （BGC823 cells： 7.6 μg/ml and 98.7%, SGC7901 cells： 12.3 μg/ml and 85.7%）; colon cancers （HT29 cells： 13.6 μg/ml and 97.2%, HCT cells： 14.5 μg/ml and 96.5%）; liver cancers （Bel7402 cells： 15.2 μg/ml and 89.2%, HepG2 cells： 7.1 μg/ml and 88.3%）; pancreatic cancer （PC3 cells： 11.3 μg/ml and 68.4%）; lung cancer （A549 cells： 18.6 μg/ml and 98.0% ）; breast cancer （MCF7 cells： 18.4 μg/ml and 84.7%）; uterine cervix cancer （Hela cells： 13.7 μg/ml and 98.5%）. CONCLUSION Oridonin had a relatively wide anti-tumor spectrum, and a relatively strong inhibitory effect on the growth of the 15 human cancer cells. Inhibitory effects were concentration dependent.

Mathematical rules for synergistic,additive,and antagonistic effects of multi-drug combinations and their application in research and development of combinatorial drugs and special medical food combinations

Multi-drug(or multi-element)combinations are often prescribed in the practice of clinical medicine and as foods for special medical purposes.The main motivations for these combinations are that most diseases contain multiple related targets and an appropriate combination can maximize benefits while minimizing adverse reactions.As such,it is especially important to derive mathematical models for their quantitative calculation.In this paper,we introduce mathematical rules for the synergistic,additive,and antagonistic effects of multi-drug combinations developed in our laboratory.We have established a“onebelt,one-line”model and provide examples of the quantitative calculation of the synergistic,additive,and antagonistic effects of a combination of multiple components.We also explain how to scientifically and precisely determine the intensity of these synergies,additions and antagonisms,as well as their corresponding dose ranges,thereby laying a solid theoretical foundation for market listing combinatorial drugs and foods for special medical purposes.

Removal of pathogenic indicator microorganisms during partial nitrification:the role of free nitrous acid

Digested wastewater contains pathogenic microorganisms and high ammonia concentrations,which can pose a potential risk to public health.Effective removal of pathogens and nitrogen is crucial for the post-treatment of digested wastewater.Partial nitrification-anammox is an energy-saving nitrogen removal process.Free nitrous acid(FNA),an intermediate product of partial nitrification,has the potential to inactivate microorganisms.However,the efficiency and mechanisms of FNA-related inactivation in pathogens during partial nitrification remains unclear.In this study,Enterococcus and Escherichia coli(E.coli)were selected to investigate the efficiency and mechanisms of FNA-related inactivation in partial nitrification process.The results revealed that 83%±13%and 59%±27%of E.coli and Enterococcus were removed,respectively,in partial nitrification process at FNA concentrations of 0.023−0.028 mg/L.When the concentration of FNA increased from 0 to 0.5 mg/L,the inactivation efficiencies of E.coli and Enterococcus increased from 0 to 99.9%and 89.9%,respectively.Enterococcus exhibited a higher resistance to FNA attack compared to E.coli.3D-laser scanning microscopy(3D-LSM)and scanning electron microscopy(SEM)revealed that FNA exposure caused the surface collapse of E.coli and Enterococcus,as well as visible pore formation on the surface of E.coli cells.4',6-Diamidino-2-phenylindole dihydrochloride n-hydrate(DAPI)/propidium iodide(PI)and biomolecule leakage confirmed that inactivation of E.coli and Enterococcus occurred due to breakdown of cell walls and cell membranes.These findings indicate that partial nitrification process can be used for the removal of residual pathogenic microorganisms.

Use of gamma-irradiation pretreatment for enhancement of anaerobic digestibility of sewage sludge

The effects of γ-irradiation pretreatment on anaerobic digestibility of sewage sludge was investigated in this paper.Parameters like solid components,soluble components,and biogas production of anaerobic digestion experiment for sewage sludge were measured.The values of these parameters were compared before and after γ-irradiation pretreatment.Total solid(TS),volatile solid(VS),suspended solid(SS),volatile suspended solid(VSS),and average floc size of samples decreased after cirradiation treatment.Besides,floc size distribution of sewage sludge shifted from 80–100 mm to 0–40 mm after γ-irradiation treatment at the doses from 0 to 30 kGy,which indicated the disintegration of sewage sludge.Moreover,microbe cells of sewage sludge were ruptured by γ-irradiation treatment,which resulted in the release of cytoplasm and increase of soluble chemical oxygen demand(SCOD).Both sludge disintegration and microbe cells rupture enhanced the subsequent anaerobic digestion process,which was demonstrated by the increase of accumulated biogas production.Compared with digesters fed with none irradiated sludge,the accumulated biogas production increased 44,98,and 178 mL for digesters fed sludge irradiated at 2.48,6.51,and 11.24 kGy,respectively.The results indicated that γ-irradiation pretreatment could effectively enhance anaerobic digestibility of sewage sludge,and correspondingly,could accelerate hydrolysis process,shorten sludge retention time of sludge anaerobic digestion process.

Impact of roxarsone on the UASB reactor performance and its degradation

Roxarsone （3-nitro-4-hydroxyphenylarsonic acid, ROX） has been widely used for decades as an organoarsenic feed additive to control intestinal parasites and improve feed efficiency in animal production. However, most of the ROX is excreted into the manure, causing arsenic contamination in wastewater. The arsenic compounds are toxic to microorganisms, but the influence of continuous ROX loading on upflow anaerobic sludge blanket （UASB） reactor is still unknown. In this study, the impact of ROX and its degradation products on the performance of the UASB reactor and the degradation and speciation of ROX in the reactor were investigated. The UASB reactor （hydraulic retention time： 1.75 d） was operated using synthetic wastewater supplemented with ROX for a period of 260 days. With continuous ROX addition at 25.0 mg.L-1, severe inhibition to methanogenic activity occurred after 87 days operation accompanied with an accumulation of volatile fatty acids （VFAs） and a decline in pH. The decrease of added ROX concentration to 13.2 mg.L-1 did not mediate the inhibition. As（III）, As （V）, MMA（V）, DMA（V）, HAPA and an unknown arsenic compound were detected in the reactor, and a possible biotransformation pathway of ROX was proposed. Mass balance analysis of arsenic indicated that 60%-70% of the arsenic was discharged into the effluent, and 30%-40% was precipitated in the reactor. The results from this study suggest that we need to pay attention to the stability in the UASB reactors treating organoarsenic-contaminated manure and wastewater, and the effluent and sludge from the reactor tO avoid diffusion of arsenic contamination.

Aggravation of membrane fouling and methane leakage by a three-phase separator in an external anaerobic ceramic membrane bioreactor

The three-phase separator is a critical component of high-rate anaerobic bioreactors due to its significant contribution in separation of biomass, wastewater, and biogas. However, its role in an anaerobic membrane bioreactor is still not clear. In this study, the distinction between an external anaerobic ceramic membrane bioreactor (EAnCMBR) unequipped (R1) and equipped (R2) with a three-phase separator was investigated in terms of treatment performance, membrane fouling, extracellular polymers of sludge, and microbial community structure. The results indicate that the COD removal efficiencies of Rl and R2 were 98.2%±0.4% and 98.1%±0.4%, respectively, but the start-up period of R2 was slightly delayed. Moreover, the membrane fouling rate of R2 (0.4 kPa/d) was higher than that of Rl (0.2 kPa/d). Interestingly, the methane leakage from R2 (0.1 L/d) was 20 times higher than that from Rl (0.005 L/d). The results demonstrate that the three-phase separator aggravated the membrane fouling rate and methane leakage in the EAnCMBR. Therefore, this study provides a novel perspective on the effects of a three-phase separator in an EAnCMBR.

Influence of arsanilic acid, Cu2＋, PO43- and their interaction on anaerobic digestion of pig manure

Arsanilic acid （ASA）, copper ion （Cuz ＋） and phosphate （PO43 ） are widely used as feed additives for pigs. Most of these three supplemented feed additives were excreted in feces and urine Anaerobic 2＋ digestion is often used for the management of pig manure. However the interaction ofASA with Cu 3 ＇ 2＋ 3 or P04 on anaerobic ＆gestlon is still not clear. In thin study, the influence ofASA, Cu , PO4- and their interaction on anaerobic digestion of pig manure and the possible mechanisms were investigated. The initial concentrations ofASA, Cu2＋ and PO43 were 0.46 mM, 2 mM and 2 mM in the anaerobic digester, respectively. The methanogenesis was severely inhibited in the assays with only ASA addition, only Cu2＋ addition and ASA ＋ PO43 addition with the inhibition index of 97.8%, 46.6% 2＋ and 82.6%, respectively, but the methanogenesis inhibition in the assay with ASA ＋ Cu addlt on was mitigated with the inhibition index of 39.4%. PO43 had no obvious impacts on the degradation of ASA. However, Cu2＋ addition inhibited the degradation of ASA, and mitigated the methanogcnesis inhibition. The existence of ASA would inhibit methanogenesis and generate more toxic inorganic arsenic compounds during anaerobic digestion, implying the limitation of anaerobic digestion for ASA- contaminated animal manure. However, the co-existence of ASA and Cu2＋ could mitigate the inhibition. These results could provide useful information for the management of anaerobic digestion of pig manure containing ASA and Cu2＋ .