Down-regulation of reduced folate carrier may result in folate malabsorption across intestinal brush border membrane during experimental alcoholism

Folate plays a critical role in maintaining normal metabolic, energy, differentiation and growth status of all mammalian cells. The intestinal folate uptake is tightly and diversely regulated, and disturbances in folate homeostasis are observed in alcoholism, attributable, in part, to intestinal malabsorption of folate. The aim of this study was to delineate the regulatory mechanisms of folate transport in intestinal absorptive epithelia in order to obtain insights into folate malabsorption in a rat model of alcoholism. The rats were fed 1 g.kg(-1) body weight of ethanol daily for 3 months. A reduced uptake of [(3)H]folic acid in intestinal brush border membrane was observed over the course of ethanol administration for 3 months. Folate transport exhibited saturable kinetics and the decreased intestinal brush border membrane folate transport in chronic alcoholism was associated with an increased K(m) value and a low V(max) value. Importantly, the lower intestinal [(3)H]folic acid uptake in ethanol-fed rats was observed in all cell fractions corresponding to villus tip, mid-villus and crypt base. RT-PCR analysis for reduced folate carrier, the major folate transporter, revealed that reduced folate carrier mRNA levels were decreased in jejunal tissue derived from ethanol-fed rats. Parallel changes were observed in reduced folate carrier protein levels in brush border membrane along the entire crypt-villus axis. In addition, immunohistochemical staining for reduced folate carrier protein showed that, in alcoholic conditions, deranged reduced folate carrier localization was observed along the entire crypt-villus axis, with a more prominent effect in differentiating crypt base stem cells. These changes in functional activity of the membrane transport system were not caused by a general loss of intestinal architecture, and hence can be attributed to the specific effect of ethanol ingestion on the folate transport system. The low folate uptake activity observed in ethanol-fed rats was found to be associated with decreased serum and red blood cell folate levels, which might explain the observed jejunal genomic hypomethylation. These findings offer possible mechanistic insights into folate malabsorption during alcoholism.     

Use of Coupled Al-Ag Bimetallic Cylindrical Nanoparticles to Improve the Photocurrent of a Thin-Film Silicon Solar Cell

In this paper, cylindrical shape coupled bimetallic plasmonic nanoparticles (NPs) were used to improve the performance of a thin-film silicon solar cell. Our design is based on the appropriate selection of the composition and morphology of the NPs to reach a cell with excellent optical properties. The specific interaction between the incident light and bimetallic NPs helps us to design better solar absorbers. Here, the FDTD method was used to evaluate the effect of cylindrical Al-Ag bimetallic NPs on the surface of a thin silicon absorber. At first, a unit cell with Al-Al paired nano-cylinders at the surface was evaluated and a photocurrent of 14.65 mA/cm² was obtained. In the case of a cell with paired Al-Ag bimetallic nano-cylinders, the photocurrent was increased to 16.15 mA/cm². This value was increased to 16.57 mA/cm² when paired polymetallic NPs were used. According to the results of this work, bimetallic and polymetallic nanoparticles can significantly improve the photocurrent of an ultra-thin silicon solar cell. The results of this work can be used to design better plasmonic-based light trapping systems for thin-film solar cells.

     

A novel spectrofluorimetric method based on a reaction with an azoisoxazoles–benzenesulfonamide derivative for determination of uranium (VI) ions in water samples

Selective fluorometric detection and determination of uranium ions is provided here using a novel fluorescent reagent, namely (E)-4-([4-hydroxynaphthalen-1-yl]diazenyl)-N-(5-methyleisoxazol-3-yl) benzenesulfonamide (U^VI reagent). The U^VI reagent offers a selective fluorescence enhancement behaviour at emission wavelength = 557 nm. The parameters affecting fluorometric detection of uranium ions, such as the pH, solvent type, ligand concentration, interaction time, and interfering ions, were investigated and adjusted. The proposed U^VI reagent can detect and determine uranium ions even at low concentrations, for which the obtained limit of detection was 0.1 ppm. Additionally, this proposed determination protocol was successfully used to detect, monitor, and determine uranium ions in actual water samples.     

Construction of a domestic wastewater disinfection filter from biosynthesized and commercial nanosilver: a comparative study

Overproduction of desired metabolites usually sacrifices cell growth. Here we report that quorum sensing (QS) can be exploited to coordinate cell growth and lactic acid production in Escherichia coli. We engineered two QS strains: one strain overexpressing acyl-homoserine lactone (AHL) synthesis genes (“ON”), the other strain overexpressing both AHL synthesis and degradation gene (aiiA) (“ON to semi-OFF”). To clarify the impact of the QS system on lactic acid production, D-lactate dehydrogenase gene ldhA was deleted from the E. coli genome, and Enhanced Green Fluorescence Protein (eGFP) was used as the reporter. Compared to the “ON” strain, the “ON to semi-OFF” strain showed delayed log growth and decreased egfp expression at stationary phase. When egfp was replaced by ldhA for lactic acid production, compared to the wild-type strain, the “ON to semi-OFF” strain demonstrated 231.9% and 117.3% increase in D-lactic acid titer and space-time yield, respectively, while the “ON” strain demonstrated 83.6%, 31%, and 36% increase in growth rate, maximum OD600, and glucose consumption rate, respectively. Quantitative real-time PCR revealed that both ldhA and the genes for phosphotransferase system were up-regulated in ldhA-overexpressing “ON” strain compared to the strain only harboring QS system. Moreover, the “ON” strain showed considerable increase in glucose consumption after a short lag phase. Compared to the reference strain harboring only ldhA gene in vector, both the “ON” and “ON to semi-OFF” strains demonstrated synchronization between cell growth and D-lactic acid production. Collectively, QS can be leveraged to coordinate microbial growth and product formation.     

Evaluation of anticancer effects of cerium oxide nanoparticles on mouse fibrosarcoma cell line

Cerium oxide nanoparticles are associated with anticancer effects. While protecting normal cells, these nanoparticles exert their anticancer effects via oxidative stress and apoptosis in the cancer cells. In this study, the anticancer properties of nanoceria on fibrosarcoma cell line are evaluated. Cerium oxide nanoparticles were synthesized by the coprecipitation method and their anticancer effects on mouse fibrosarcoma tumor cells (WEHI164) were investigated. Viability assay was evaluated by MTT, and the DC-FDA assay performed for the detection of reactive oxygen species. For apoptosis assay, the annexin V/PI test was done as well as measuring the mRNA and protein expression levels of Bax and Bcl2 by real-time PCR and western blot method, respectively. Characterization of nanoceria reveals that synthesized nanoceria has cubic floruit structure with a size of about 30 nm. Toxicity assessment results show that nanoceria increases ROS levels and induced apoptosis in a dose-dependent manner in cancer cells (WEHI164), whereas low levels of toxicity were observed in normal cells (L929), even at the concentrations above 250 µg/ml in MTT assay. Real-time PCR and western blot assays showed that nanoceria could significantly increase the Bax expression in cancer cells. The results showed that nanoceria could act as a potential therapeutic agent for the treatment of fibrosarcoma.     

PNU-74654 enhances the antiproliferative effects of 5-FU in breast cancer and antagonizes thrombin-induced cell growth via the Wnt pathway

The Wnt/β-catenin pathway is one of the most common pathways dysregulated in breast cancer, and may, therefore, be a potential-therapeutic target. We have investigated the effects of PNU-74654 in breast cancer, as a Wnt/β-catenin inhibitor, either alone or in combination with fluorouracil (5-FU). PNU-74654 suppressed cell growth at an IC ₅₀ of 122 ± 0.4 μmol/L and synergistically enhanced the antiproliferative activity of gemcitabine by modulating the Wnt pathway. Using a 3D cell culture model, we found that the PNU-74654 caused tumor shrinkage. It reduced the migration of MCF-7 cells (by an 18% reduction in invasive behavior) after the treatment with PNU-74654 through perturbation of E-cadherin and MMP3/9. PNU-74654/5-FU combination enhanced the percentages of cells in S-phase and significantly increased apoptosis. Moreover, our data showed that this agent was able to inhibit the growth of tumor in a xenograft model, although this effect was more pronounced in the animals treated with PNU-74654 plus 5-FU. These data show the ability of PNU-74654 to specifically target Wnt pathway, interfere with cell proliferation, induce-apoptosis, reduce-migration, and synergistically interact with 5-FU, supporting further studies on this novel therapeutic-approach for breast cancer.     

Exosomes as a novel cell-free therapeutic approach in gastrointestinal diseases

Cell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantages alongside and/or over cell therapy. However, cell therapy had a hopeful outcome in gastrointestinal diseases which have minimal alternatives in their treatments. Inflammatory bowel disease (IBD), liver fibrosis, gastrointestinal cancers are the examples that cell therapy and immunotherapy were applied in their treatment, therefore, the cell products like exosomes are the beneficial option in their treatment even cancers with promising results in animal models. In this review, we consider the main defined biogenesis, function, and component of secreted exosomes in different cells with a specific focus on the potential application of these exosomes as a cell-free therapeutic approach in gastrointestinal diseases like IBD, gastric cancer, and colon cancer. Additionally, exosomes role as therapeutic reagents mainly mesenchymal stem cells and dendritic cell-derived exosomes in different studies have been under intense investigation and even they are being studied in different clinical trials. Therefore, all these striking functions described for secretome implies the importance of these biocarriers.