Research on anti-hepatocellular carcinoma activity and mechanism of Polygala fallax Hemsl.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala fallax Hemsl. is a kind of traditional medicine of Yao Minority in China. In Chinese medicine practice, Polygala fallax Hemsl. is commonly prescribed to treat all kinds of acute and chronic hepatitis. AIM OF THE STUDY: The present study aimed at investigating the effects and its possible mechanism of Polygala fallax Hemsl. on the proliferation and apoptosis of HepG2 cells (a kind of human hepatoma cell). MATERIALS AND METHODS: Through a variety of experimental methods, including MTT technique and Hoechst staining to detect apoptosis in Hepatocyte HepG2 cells, flow cytometry to observe the pro-apoptotic and circulatory arrest effects as well as real-time fluorescence quantitative polymerase chain reaction (q-PCR) technique to examine the expression levels of Bcl-2/Bax gene and prote Western blot to examine the expression levels of bcl-2/bax,caspase3,8,9,CyclinA,p21,p27,ERK.Phospho-ERK and AKT, Phospho-AKT in HepG2 cells. RESULTS: The results showed that compared with the control group, all polarity fractions of P. fallax had inhibitory effects on HepG2 cells, among which the inhibition effect of ethyl acetate fraction in 0.036 ± 0.001 mg/mL of IC50 for 24 h was the most obvious (P < 0.01). And the HepG2 cells induced at the ethyl acetate fraction could up-regulate Bax gene and protein, while down-regulating Bcl-2 gene and protein (P < 0.05) during S phase in a dose-dependent manner. In addition, the ethyl acetate site of Larch can also down regulate the expression of ERK, AKT and activate caspase 3, 8 and 9. CONCLUSION: It could be concluded that the ethyl acetate fraction of Polygala fallax Hemsl. can significantly prohibit the proliferation of HepG2 cells. The possible mechanism is to promote the expression of Bax, inhibit the expression of Bcl-2, and down regulate the expression of AKT and ERK.

Genetic elimination of field-cage populations of Mediterranean fruit flies.

The Mediterranean fruit fly (medfly, Ceratitis capitata Wiedemann) is a pest of over 300 fruits, vegetables and nuts. The sterile insect technique (SIT) is a control measure used to reduce the reproductive potential of populations through the mass release of sterilized male insects that mate with wild females. However, SIT flies can display poor field performance, due to the effects of mass-rearing and of the irradiation process used for sterilization. The development of female-lethal RIDL (release of insects carrying a dominant lethal) strains for medfly can overcome many of the problems of SIT associated with irradiation. Here, we present life-history characterizations for two medfly RIDL strains, OX3864A and OX3647Q. Our results show (i) full functionality of RIDL, (ii) equivalency of RIDL and wild-type strains for life-history characteristics, and (iii) a high level of sexual competitiveness against both wild-type and wild-derived males. We also present the first proof-of-principle experiment on the use of RIDL to eliminate medfly populations. Weekly releases of OX3864A males into stable populations of wild-type medfly caused a successive decline in numbers, leading to eradication. The results show that genetic control can provide an effective alternative to SIT for the control of pest insects.

Population-level effects of fitness costs associated with repressible female-lethal transgene insertions in two pest insects.

Genetic control strategies offer great potential for the sustainable and effective control of insect pests. These strategies involve the field release of transgenic insects with the aim of introducing engineered alleles into wild populations, either permanently or transiently. Their efficacy can therefore be reduced if transgene-associated fitness costs reduce the relative performance of released insects. We describe a method of measuring the fitness costs associated with transgenes by analyzing their evolutionary trajectories when placed in competition with wild-type alleles in replicated cage populations. Using this method, we estimated lifetime fitness costs associated with two repressible female-lethal transgenes in the diamondback moth and olive fly as being acceptable for field suppression programs. Furthermore, using these estimates of genotype-level fitness costs, we were able to project longer-term evolutionary trajectories for the transgenes investigated. Results from these projections demonstrate that although transgene-associated fitness costs will ultimately cause these transgenes to become extinct, even when engineered lethality is repressed, they may persist for varying periods of time before doing so. This implies that tetracycline-mediated transgene field persistence in these strains is unlikely and suggests that realistic estimates of transgene-associated fitness costs may be useful in trialing 'uncoupled' gene drive system components in the field.

The impact of bed-net use on malaria prevalence.

Malaria infection continues to be a major problem in many parts of the world including the Americas, Asia, and Africa. Insecticide-treated bed-nets have shown to reduce malaria cases by 50%; however, improper handling and human behavior can diminish their effectiveness. We formulate and analyze a mathematical model that considers the transmission dynamics of malaria infection in mosquito and human populations and investigate the impact of bed-nets on its control. The effective reproduction number is derived and existence of backward bifurcation is presented. The backward bifurcation implies that the reduction of R below unity alone is not enough to eradicate malaria, except when the initial cases of infection in both populations are small. Our analysis demonstrate that bed-net usage has a positive impact in reducing the reproduction number R. The results show that if 75% of the population were to use bed-nets, malaria could be eliminated. We conclude that more data on the impact of human and mosquito behavior on malaria spread is needed to develop more realistic models and better predictions.

Control of the olive fruit fly using genetics-enhanced sterile insect technique.

BACKGROUND: The olive fruit fly, Bactrocera oleae, is the major arthropod pest of commercial olive production, causing extensive damage to olive crops worldwide. Current control techniques rely on spraying of chemical insecticides. The sterile insect technique (SIT) presents an alternative, environmentally friendly and species-specific method of population control. Although SIT has been very successful against other tephritid pests, previous SIT trials on olive fly have produced disappointing results. Key problems included altered diurnal mating rhythms of the laboratory-reared insects, resulting in asynchronous mating activity between the wild and released sterile populations, and low competitiveness of the radiation-sterilised mass-reared flies. Consequently, the production of competitive, male-only release cohorts is considered an essential prerequisite for successful olive fly SIT. RESULTS: We developed a set of conditional female-lethal strains of olive fly (named Release of Insects carrying a Dominant Lethal; RIDL®), providing highly penetrant female-specific lethality, dominant fluorescent marking, and genetic sterility. We found that males of the lead strain, OX3097D-Bol, 1) are strongly sexually competitive with wild olive flies, 2) display synchronous mating activity with wild females, and 3) induce appropriate refractoriness to wild female re-mating. Furthermore, we showed, through a large proof-of-principle experiment, that weekly releases of OX3097D-Bol males into stable populations of caged wild-type olive fly could cause rapid population collapse and eventual eradication. CONCLUSIONS: The observed mating characteristics strongly suggest that an approach based on the release of OX3097D-Bol males will overcome the key difficulties encountered in previous olive fly SIT attempts. Although field confirmation is required, the proof-of-principle suppression and elimination of caged wild-type olive fly populations through OX3097D-Bol male releases provides evidence for the female-specific RIDL approach as a viable method of olive fly control. We conclude that the promising characteristics of OX3097D-Bol may finally enable effective SIT-based control of the olive fly.

Genetic elimination of dengue vector mosquitoes.

An approach based on mosquitoes carrying a conditional dominant lethal gene (release of insects carrying a dominant lethal, RIDL) is being developed to control the transmission of dengue viruses by vector population suppression. A transgenic strain, designated OX3604C, of the major dengue vector, Aedes aegypti, was engineered to have a repressible female-specific flightless phenotype. This strain circumvents the need for radiation-induced sterilization, allows genetic sexing resulting in male-only releases, and permits the release of eggs instead of adult mosquitoes. OX3604C males introduced weekly into large laboratory cages containing stable target mosquito populations at initial ratios of 8.5-101 OX3604Ctarget eliminated the populations within 10-20 weeks. These data support the further testing of this strain in contained or confined field trials to evaluate mating competitiveness and environmental and other effects. Successful completion of the field trials should facilitate incorporation of this approach into area-wide dengue control or elimination efforts as a component of an integrated vector management strategy.

Climate-based models for West Nile Culex mosquito vectors in the Northeastern US.

Climate-based models simulating Culex mosquito population abundance in the Northeastern US were developed. Two West Nile vector species, Culex pipiens and Culex restuans, were included in model simulations. The model was optimized by a parameter-space search within biological bounds. Mosquito population dynamics were driven by major environmental factors including temperature, rainfall, evaporation rate and photoperiod. The results show a strong correlation between the timing of early population increases (as early warning of West Nile virus risk) and decreases in late summer. Simulated abundance was highly correlated with actual mosquito capture in New Jersey light traps and validated with field data. This climate-based model simulates the population dynamics of both the adult and immature mosquito life stage of Culex arbovirus vectors in the Northeastern US. It is expected to have direct and practical application for mosquito control and West Nile prevention programs.