Safety,immunogenicity,and cross-species protection of a plasmid DNA encoding Plasmodium falciparum SERA5 polypeptide,microbial epitopes and chemokine genes in mice and olive baboons

Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of straintranscending malarial vaccines.The present study sought to determine safety,immunogenicity and cross-species efficacy of Plasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of BacilleCalmette Guerin（BCG）,tetanus toxoid（TT） and a chemokine gene.Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups.The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5 ＋ BCG ＋ TT alone,or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone.Mice and baboons were challenged with P.berghei ANKA and P.knowlesi H strain parasites,respectively.Safety was determined by observing for injection sites reactogenicities,hematology and clinical chemistry.Parasitaemia and survivorship profiles were used to determine cross-species efficacy,and T cell phenotypes,Th1-,Th2-type,T-regulatory immune responses and antibody responses were assessed to determine vaccine immunogenicity.The pSeBCGTT plasmid DNA vaccines were safe and induced Thl-,Th2-type,and Tregulatory responses vaccinated animals showed enhanced CD4~＋（P〈0.01）,CD 8~＋ T cells（P〈 0.001） activation and IgG anti-SE36 antibodies responses（P〈 0.001） at week 4 and 8 post vaccination compared to the control group.Vaccinated mice had a 31.45-68.69%cumulative parasite load reduction and 60%suppression in baboons（P〈0.05）and enhanced survivorship（P〈 0.001） with no clinical signs of malaria compared to the control group.The results showed that the vaccines were safe,immunogenic and conferred partial cross-species protection.

EFFECT OF GLYCYRRHETINIC ACID ON DNA DAMAGE AND UNSCHEDULED DNA SYNTHESIS INDUCED BY BENZO（α）PYRENE

Glyeyrrhetinic acid (GA) is an active component of Glycyrrhiza uraleusis fisch,In this study,GA was found to inhibit ear edema and ornithine decarboxylase (ODC)activity induced by croton oil in mice. GA could also protect rapid DNA damage and decrease the unscheduled DNA synthesis induced by benzo(α)pyrene. The results demonstrate that GA has a potential cancer chemopreventive activity.

Galantamine protects against beta amyloid peptide-induced DNA damage in a model for Alzheimer's disease

Alzheimer’s disease（AD）is the most common type of dementia in elderly population.With a growing aging population not only in the United States but also in the worldwide,AD constitutes an emergent public health problem.

Protective effect of rhizome extracts of the herb, vacha (Acorus calamus) against oxidative damage: An in vivo and in vitro study

The rhizome of Acorus calamus,an herb widely used in Indian system of medicine for many ailments including epilepsy,mental illness and rheumatism,was subjected to soxhlet extraction to elucidate antioxidant property of different solvent extracts using in vitro assays.The benzene extract was most potent in scavenging hydroxyl and superoxide radicals and in reducing 1,1-diphenyl-2-picryl hydrazyl and ferric reducing antioxidant power.In addition the benzene extract prevented oxidative damage to DNA and mitochondria.It was also effective in preventing stress-induced decrease in total plasma anti-oxidant activity as determined in vivo using rat model wherein stress was induced by exposing to restraint and forced swimming.The minimum effective dose of the benzene extract was 5 mg/kg body weight(oral),and at this dose,its effect was similar to the same dose of a standard anti-oxidant,ascorbic acid.The study for the first time,clearly demonstrates a potent anti-oxidant activity of A.calamus combining in vitro and in vivo results.Hence,the therapeutic value of this herb maybe due to its anti-oxidant property.©2016 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Simultaneous quantification of ten constituents of Xanthoceras sorbifolia Bunge using UHPLC-MS methods and evaluation of their radical scavenging, DNA scission protective, and α-glucosidase inhibitory activities

The present study was designed to investigate the bioactive constituents ofXanthoceras sorbifolia in terms of amounts and their antioxidant, DNA scissiou protection, and ct-glucosidase inhibitory activities. Simultaneous quantification of 10 X. sorbifolia constituents was carried out by a newly established ultra-high performance liquid chromatography-quadrupole mass spectrometry method （UHPLC-MS）, The antioxidant activities were evaluated by measuring DPPH radical scavenging and DNA scission protective activities. The a-glucosidase inhibitory activities were investigated by using an assay with a-glucosidase from Bacillus Stearothermophilus and disaccharidases from mouse intestine. We found that the wood ofX. sorbifolia was rich in phenolic compounds with the contents of catechin, epicatechin, myricetin, and dihydromyricetin being 0.12-0.19, 1.94-2.16, 0.77-0.91, and 6.76-7.89 mg.g-1, respectively. The four constituents strongly scavenged DPPH radicals （with ECs0 being 4.2, 3.8 and 5.7 μg-mL-1, respectively） and remarkably protected peroxyl radical-induced DNA strand scission （92.10%, 94.66%, 75.44% and 89.95% of protection, respectively, at a concentration of 10 μmol.L-1）. A dimeric flavan 3-ol, epigallocatechin-（4β→8, 2β→O-7）-epicatechin potently inhibited a-glucosidase with an IC50 value being as low as 1.2 μg.mL1. The established UHPLC-MS method could serve as a quality control tool for X. sorbifolia. In conclusion, the high contents of antioxidant and α-glucosidase inhibitory constituents in X. sorbifolia support its use as complementation of other therapeutic agents for metabolic disorders, such as diabetes and hypertension.

Immune responses against Schistosoma japonicum after vaccinating mice with a multivalent DNA vaccine encoding integrated membrane protein Sj23 and cytokine interleukin-12

Background The vaccination of mice with DNA encoding single candidate antigens has failed to induce significant protection against Schistosoma japonicum (S. japonicum) challenge infections In this study, we evaluated the feasibility of using a multivalent DNA vaccine which co expressed S japonicum integral membrane protein Sj23 and murine cytokine IL 12 to induce protective immune responses Methods The plasmid pVIVO2 IL12 Sj23, a eukaryotic expression vector expressing Sj23 and murine IL 12 simultaneously, was constructed, identified, and tested for expression in vitro Its ability to protect against S japonicum challenge infections was analyed according to worm reduction rate and egg reduction rate after vaccination of BALB/c mice The serum levels of specific IgG antibody were determined by enzyme linked immuno sorbent assay (ELISA) and Western blot analysis Using cultured spleen cells, IFN γ and IL 4 post stimulation were quantified by ELISA The phenotypes of splenocyte populations were analyzed by flow cytometry (FCM) Results The plasmid DNA pVIVO2 IL12 Sj23 was proven to express well in vitro by transient transfection of HEK 293 cells Immunization resulted in a worm reduction rate of 45 53% and egg reduction rate of 58 35% ELISA and Western blot analysis indicated that immunized mice generated specific IgG against Sj23 Spleen cells showed significant increases in IFN γ but decreases in IL 4 No significant differences in CD4 + and CD8 + subgroup ratios were observed after the challenges Conclusions The multivalent DNA vaccine pVIVO2 IL12 Sj23 is sufficient to elicit moderate but highly significant levels of protective immunity against challenge infections Cytokine IL 12, as a gene adjuvant, was able to enhance the Th1 responses and, hence, the protective immunity

Antioxidative properties of phenolic compounds isolated from the fungal endophytes of Zingiber nimmonii （J. Graham） Dalzell.

BACKGROUND： The microbes living in planta termed ＇endophytes＇ is bestowed with the potential to produce bioactive substances. The aim of this investigation was focused on the isolation and molecular identification of the fungal endophytes from Zingiber nimmonii （J. Graham） Dalzell., an endemic medicinal plant species of the ＇Western ghats＇, a hotspot location in southern India and characterization of the secondary metabolites responsible for the ant^oxidant and DNA protective capacity using chromatography and mass spectrometry techniques. METHODS： Endophytic fungi were isolated and identified by sequencing the Internal Transcribed Spacer （ITS）. The secondary metabolites were extracted with ethyl acetate and evaluated for the total phenolic, flavonoid and antioxidant capacities. The isolates with potential antioxidative property were further analyzed for the DNA protection ability and the presence ofbioactive phenolic compounds by High Performance Liquid Chromatography （HPLC） and Electrospray Ionization- Mass Spectroscopy/Mass Spectroscopy （ESI-MS/MS） techniques. RESULTS： Endophytic fungi belonging to 11 different taxa were identified. The total phenolic content of the extracts ranged from 10.8±0.7 to 81.6±6.0 mg gallic acid equivalent/g dry extract. F lavonoid was present in eight extracts in the range of 5.2 ±0.5 to 24.3±0.9 mg catechin equivalents/g dry extract. Bipolaris specifera, Alternaria tenuissima, Aspergillus terreus, Nectria haematococca and Fusarium chlamydosporum extracts exhibited a potentially high ant^oxidant capacity. Characterization of the extracts revealed an array of phenolic acids and flavonoids. N. haematococca and E chlamydosporum extracts contained quercetin and showed DNA protection ability. CONCLUSION： This study is the first comprehensive report on the fungal endophytes from Z. nimmonii, as potential sources of antioxidative and DNA protective compounds. The study indicates that Z. nimmonii endophytes are potential sources of antioxidants over the plant itself

Biotransformation of soy whey into a novel functional beverage by Cordyceps militaris SN-18

Soy whey,a liquid nutritional by-product of soybean manufacture,is rich in proteins,oligosaccharides and isoflavones.Soy whey can be used to produce functional beverages,instead of discarding it as a waste.In this study,unfermented soy whey(USW)and Cordyceps militaris SN-18-fermented soy whey(FSW)were investigated and compared for their physicochemical and functional properties by high performance liquid chromatography(HPLC)and DNA damage assay.Results show that C.militaris SN-18 fermentation could increase the contents of essential amino acids,total phenolic and flavonoid and isoflavone aglycones and eliminate the oligosaccharides in soy whey.Furthermore,C.militaris SN-18 could significantly enhance the ABTS radical scavenging ability,reducing power and ferric reducing power of soy whey,and its fermented products could prominently attenuate Fenton reaction-induced DNA damage.These findings indicate that soy whey can potentially be converted into a novel soy functional beverage by C.militaris SN-18 fermentation.