Comparative study of cytotoxicity and oxidative stress induced by deoxynivalenol, zearalenone or fumonisin B1 in human intestinal cell line Caco-2

Fusarium species infestations of cereals crops occur worldwide. Fusarium toxins such as, deoxynivalenol (DON), zearalenone (ZEN) and fumonisin B1 (FB1) have been shown to cause diverse toxic effects in animals and also suspected of disease causation in humans. From the literature and mechanistic point of view, DON binds to the ribosomal peptidyl-transferase and inhibits protein synthesis specifically and DNA synthesis consequently. ZEN known to be genotoxic, binds to 17-beta-estradiol receptors, induces lipid peroxidation, cell death and inhibits protein and DNA synthesis. FB1 disrupts sphingolipid metabolism, induces lipid peroxidation altering the cell membrane and causing cell death. We intended to compare DON, ZEN and FB1 (1-150 microM) cytotoxic effect and the pathways leading to cell death and related to oxidative stress and macromolecules syntheses in a human intestinal cell line in order to tentatively classify them according to their respective potential toxicity. The comparison reveals that all three mycotoxins bear, at variable degree, the capability of inducing lipid peroxidation (MDA production) and could be classified above 10 microM in decreasing potency order FB1>DON>ZEN. This effect seems to be related to their common target that is the mitochondria as revealed by MTT test and seemingly not related to sphingoids accumulation concerning FB1. DON and ZEN also adversely affect lysosomes in contrast to FB1. The three mycotoxins inhibit protein synthesis with respective IC50 of 5, 8.8 and 19 microM for DON, FB1 and ZEN confirming that protein synthesis is a specific target of DON. DNA synthesis is inhibited by DON, ZEN and FB1 with respective IC50 of 1.7, 10 and 20 microM. However at higher concentrations DNA synthesis seems to be restored for FB1 and DON suggesting a promoter activity. Altogether the potency of the three mycotoxins in macromolecules inhibition is DON>ZEN>FB1 in Caco-2 cells. It appears then that FB1 acts rather through lipid peroxidation while DON affects rather DNA and protein synthesis.     

Note on the formulation of thermosensitive and mucoadhesive vaginal hydrogels containing the miniCD4 M48U1 as anti-HIV-1 microbicide

The miniCD4 M48U1 was formulated into thermosensitive and mucoadhesive pluronic^® hydrogels as anti-HIV-1 microbicide. The release kinetics of M48U1 from F127/HPMC (20/1 wt%) and F127/F68/HPMC (22.5/2.5/1 wt%) studied during 24 h by using Franz diffusion cells showed that HEC hydrogel (1.5 wt%) used as control released 93% of the peptide, while about 25% of M48U1 remained in pluronic^® hydrogels. The formulation of M48U1 in pluronic^® hydrogels ensures a local delivery because no diffusion of the peptide was detected through vaginal Cynomolgus macaque mucosa using Ussing chamber. Finally, toxicological studies showed no significant difference in the HeLa cell viability of the pluronic^® hydrogels in comparison with HEC and phosphate buffer saline.     

Bioassay-Guided Isolation of Antimalarial Triterpenoid Acids from the Leaves of Morinda lucida.

Abstract

The EtOH, CH₂Cl₂, and petroleum ether extracts from Morinda lucida. Benth. leaves have been shown to exhibit an in vitro. antiplasmodial activity against a chloroquine-sensitive Plasmodium falciparum. strain with IC₅₀ values 5.7 ± 1.3, 5.2 ± 0.8, and 3.9 ± 0.3 µg/mL, respectively. In vivo., at a daily oral dose of 200 mg/kg body weight, they produced at least 62.5%, 67.5%, and 72.2% reduction of parasitemia in mice infected with Plasmodium berghei berghei., respectively. A bioassay-guided fraction of the most active petroleum ether extract resulted in the isolation of two known triterpenic acids as ursolic acid 1 and oleanolic acid 2. In vitro., 1 and 2 exhibited an antiplasmodial activity with IC₅₀ values of 3.1 ± 1.3 and 15.2 ± 3.4 µg/mL, respectively. In vivo., at a daily dose of 200 mg/kg body weight, they produced 97.7% and 37.4% chemosuppression, respectively. However, all tested samples were inactive in vitro. against chloroquine-resistant Plasmodium falciparum. (K1) at the highest tested concentration of 25 µg/mL.     

Passive surveillance for I. scapularis ticks: enhanced analysis for early detection of emerging Lyme disease risk

Lyme disease (LD) is emerging in Canada because of the northward expansion of the geographic range of the tick vector Ixodes scapularis (Say). Early detection of emerging areas of LD risk is critical to public health responses, but the methods to do so on a local scale are lacking. Passive tick surveillance has operated in Canada since 1990 but this method lacks specificity for identifying areas where tick populations are established because of dispersion of ticks from established LD risk areas by migratory birds. Using data from 70 field sites in Quebec visited previously, we developed a logistic regression model for estimating the risk of I. scapularis population establishment based on the number of ticks submitted in passive surveillance and a model-derived environmental suitability index. Sensitivity-specificity plots were used to select an optimal threshold value of the linear predictor from the model as the signal for tick population establishment. This value was used to produce an "Alert Map" identifying areas where the passive surveillance data suggested ticks were establishing in Quebec. Alert Map predictions were validated by field surveillance at 76 sites: the prevalence of established I. scapularis populations was significantly greater in areas predicted as high-risk by the Alert map (29 out of 48) than in areas predicted as moderate-risk (4 out of 30) (P < 0.001). This study suggests that Alert Maps created using this approach can provide a usefully rapid and accurate tool for early identification of emerging areas of LD risk at a geographic scale appropriate for local disease control and prevention activities.     

Damage Characterization of Bio and Green Polyethylene–Birch Composites under Creep and Cyclic Testing with Multivariable Acoustic Emissions

Despite the knowledge gained in recent years regarding the use of acoustic emissions (AEs) in ecologically friendly, natural fiber-reinforced composites (including certain composites with bio-sourced matrices), there is still a knowledge gap in the understanding of the difference in damage behavior between green and biocomposites. Thus, this article investigates the behavior of two comparable green and biocomposites with tests that better reflect real-life applications, i.e., load-unloading and creep testing, to determine the evolution of the damage process. Comparing the mechanical results with the AE, it can be concluded that the addition of a coupling agent (CA) markedly reduced the ratio of AE damage to mechanical damage. CA had an extremely beneficial effect on green composites because the Kaiser effect was dominant during cyclic testing. During the creep tests, the use of a CA also avoided the transition to new damaging phases in both composites. The long-term applications of PE green material must be chosen carefully because bio and green composites with similar properties exhibited different damage processes in tests such as cycling and creep that could not be previously understood using only monotonic testing.     

Staphylococcus aureus Extracellular Vesicles: A Story of Toxicity and the Stress of 2020

Staphylococcus aureus generates and releases extracellular vesicles (EVs) that package cytosolic, cell-wall associated, and membrane proteins, as well as glycopolymers and exoproteins, including alpha hemolysin, leukocidins, phenol-soluble modulins, superantigens, and enzymes. S. aureus EVs, but not EVs from pore-forming toxin-deficient strains, were cytolytic for a variety of mammalian cell types, but EV internalization was not essential for cytotoxicity. Because S. aureus is subject to various environmental stresses during its encounters with the host during infection, we assessed how these exposures affected EV production in vitro. Staphylococci grown at 37 °C or 40 °C did not differ in EV production, but cultures incubated at 30 °C yielded more EVs when grown to the same optical density. S. aureus cultivated in the presence of oxidative stress, in iron-limited media, or with subinhibitory concentrations of ethanol, showed greater EV production as determined by protein yield and quantitative immunoblots. In contrast, hyperosmotic stress or subinhibitory concentrations of erythromycin reduced S. aureus EV yield. EVs represent a novel S. aureus secretory system that is affected by a variety of stress responses and allows the delivery of biologically active pore-forming toxins and other virulence determinants to host cells.     

Short-term increase in unsafe sexual behaviour after initiation of HAART in Côte d'Ivoire

A study of 312 untreated and 303 HAART-initiating patients to determine whether HAART is related to sexual risk taking in C?te d'Ivoire. At enrollment, unprotected sex was higher among untreated patients (P = 0.014). During follow-up, risk taking was similar (P = 0.484) as a result of an increase in unprotected sex among treated patients (from 20.4 to 30.1%, P < 0.0001) and stability among untreated patients (from 27.0 to 28.8%, P = 0.301). HAART appeared to be associated with sexual risk taking.