Co-delivery with nano-quercetin enhances doxorubicin-mediated cytotoxicity against MCF-7 cells

Quercetin, the plant-derived phenolic compounds, plays a pivotal role in controlling hemostasis, by having potent antioxidant and free-radical scavenging properties. This flavonoid in combination with chemotherapeutic drugs improves the efficacy of these agents in induction of apoptosis in cancer cells. This study investigated the role of nano-quercetin (phytosome) in doxorubicin-induced apoptosis. Nanoparticles were characterized for particle size, zeta potential, scanning electron microscopy (SEM) and differential scanning calorimetric assessments. Anti-proliferative effect of formulations was evaluated by MTT assay. mRNA expression levels of target genes were measured by real time RT-PCR. The mean size of nanoparticles was 85 ± 2 nm with nearly narrow size distribution which was confirmed by SEM analysis. Our results showed that co-treatment of MCF-7 breast cancer cells with nano-quercetin and doxorubicin increased the percentage of apoptosis from 40.11 ± 7.72–58 ± 7.13 (p < 0.05). Furthermore, mRNA expression levels for downstream genes including NQO1 and MRP1 showed a marked decrease (p < 0.05). Taken together, our results suggest that phytosome technology can elevate the efficacy of chemotherapeutics by increasing the permeability of tumor cells to chemical agents. Our findings introduce a novel phytosome-dependent strategy to improve delivery of doxorubicin to the breast cancerous tissues.     

Nonequilibrium single molecule protein folding in a coaxial mixer

We have developed a continuous-flow mixing device suitable for monitoring bioconformational reactions at the single-molecule level with a response time of ∼10 ms under single-molecule flow conditions. Its coaxial geometry allows three-dimensional hydrodynamic focusing of sample fluids to diffraction-limited dimensions where diffusional mixing is rapid and efficient. The capillary-based design enables rapid in-lab construction of mixers without the need for expensive lithography-based microfabrication facilities. In-line filtering of sample fluids using granulated silica particles virtually eliminates clogging and extends the lifetime of each device to many months. In this article, to determine both the distance-to-time transfer function and the instrument response function of the device we characterize its fluid flow and mixing properties using both fluorescence cross-correlation spectroscopy velocimetry and finite element fluid dynamics simulations. We then apply the mixer to single molecule FRET protein folding studies of Chymotrypsin Inhibitor protein 2. By transiently populating the unfolded state of Chymotrypsin Inhibitor Protein 2 (CI2) under nonequilibrium in vitro refolding conditions, we spatially and temporally resolve the denaturant-dependent nonspecific collapse of the unfolded state from the barrier-limited folding transition of CI2. Our results are consistent with previous CI2 mixing results that found evidence for a heterogeneous unfolded state consisting of cis- and trans-proline conformers.     

Effects of PM2.5 and NO2 on the 8-isoprostane and lung function indices of FVC and FEV1 in students of Ahvaz city,Iran

The aim of this study was to determine the correlation between PM_2.5 and NO₂ pollutants and oxidative stress marker (8-isoprostane) and lung function tests (FVC and FEV₁) in healthy children who were living and studying in three different areas of Ahvaz city including A₁: Naderi site with high traffic, A₂: Alavi Alley site with average traffic, and A₃: Ein 2 site with low traffic (a rural area on the suburb of Ahvaz). 30 students in the 12–13 year-old range were selected from each studied zone (1, 2 and 3 sites) during three months of year. Of each student, one sample was taken every two weeks to measure 8-isoprostane of exhaled breath condensate (EBC). Air pollution data were collected from three air quality monitoring stations. Also, the relationship between air pollution and 8-isoprostane as well as lung function tests were determined using generalized estimating equations (GEE). The mean concentration of PM_2.5 and NO₂ in A₁, A₂ and A₃ areas were 116, 92 and 45 (μg/m³) also 77, 53 and 14 (ppb) respectively. Among all studied students, there was a significant correlation between the increase of mean concentration of PM_2.5 and NO₂ in 1–4 before sampling day, increased 8-isoprostane concentration and decreased FEV₁, while there was no significant correlation between them and decreased FVC. In A₁ site, an increase in IQR (13 μg/m³) PM_2.5 and IQR (6.5 ppb) NO₂ on 1–4 days before sampling was associated with 0.38 unit (95% CI: 0.11, 0.65) and 1.1 unit (95% CI: 0.85, 1.35) increase in 8-isoprostane concentration, also decreased 121 ml and 190 ml FEV₁, respectively. Results showed that the short-term exposure to traffic-related air pollution can decrease the values of lung function indices and increase the oxidative stress. It may adversely affect children’s lungs.     

The role of the S1 binding site of carboxypeptidase M in substrate specificity and turn-over

The influence of the P1 amino acid on the substrate selectivity, the catalytic parameters K(m) and k(cat), of carboxypeptidase M (CPM) (E.C. 3.4.17.12) was systematically studied using a series of benzoyl-Xaa-Arg substrates. CPM had the highest catalytic efficiency (k(cat)/K(m)) for substrates with Met, Ala and aromatic amino acids in the penultimate position and the lowest with amino acids with branched side-chains. Substrates with Pro in P1 were not cleaved in similar conditions. The P1 substrate preference of CPM differed from that of two other members of the carboxypeptidase family, CPN (CPN/CPE subfamily) and CPB (CPA/CPB subfamily). Aromatic P1 residues discriminated most between CPM and CPN. The type of P2 residue also influenced the k(cat) and K(m) of CPM. Extending the substrate up to P7 had little effect on the catalytic parameters. The substrates were modelled in the active site of CPM. The results indicate that P1-S1 interactions play a role in substrate binding and turn-over.     

Life-history parameters of the western flower thrips,Frankliniella occidentalis,are affected by host plant salinity stress

Salinization, as one of the foremost abiotic stresses, is an intensifying problem in many agroecosystems. Climatic changes, along with altering land use and also salinity of irrigation water all lead to enhanced soil salinity in agricultural lands. Changes in plant characteristics, as a result of raising soil salinity, may impose bottom-up impact on plant-feeding insects. We assessed the bottom-up impact of salinity stress on demographic traits of the western flower thrips (WFT), Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), on cherry tomato, Solanum lycopersicum L. var. cerasiforme (Solanaceae) plants under greenhouse conditions (27 ± 2 °C, 65 ± 5% r.h., and L16:D8 photoperiod). Our results indicated that salinity stress interfered with the immature development period, adult longevity, and sex ratio of WFT. Salinity stress biased the sex ratio in favor of males. Significant concentration-dependent differences were observed in the intrinsic (r) and finite (λ) increase rates and the net reproduction rate (R₀) of WFT at different salinity levels. Salinity adversely influenced WFT development; nonetheless, population projection forecasted an ascending WFT population growth under moderate salinity stress of 100 mM (2.8 dS m⁻¹ of NaCl), whereas severe salinity stress of 150 mM (4.7 dS m⁻¹ of NaCl) resulted in remarkable fitness costs in WFT. This study demonstrates that WFT has the potential to become problematic in regions with moderate salinity. Therefore, it might exacerbate the detrimental impact of salinity on tomato production. The current survey provides information on the abundance of WFT on saline-stressed tomato plants, thereby contributing to developing environmentally friendly measures to manage this notorious species in ecosystems under salinity stress.