The effect of alpha-tocopherol and beta-carotene supplementation on COPD symptoms

The effects of alpha-tocopherol (50 mg/d) and beta-carotene (20 mg/d) supplementation on symptoms of chronic obstructive pulmonary disease were studied among the 29,133 participants of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study undertaken to investigate the effects of these two substances in the prevention of lung and other cancers. During the follow-up the supplementations did not affect the recurrence or incidence of chronic cough, phlegm, or dyspnea. The prevalence of chronic bronchitis and dyspnea at baseline was lower among those with high dietary intake of beta-carotene (OR = 0.78 and 0.67, respectively) or vitamin E (OR = 0.87 and 0.77) and high serum beta-carotene (OR = 0.59 and 0.62) and alpha-tocopherol (OR = 0.76 and 0.82). High intake and serum levels of retinol were associated with low prevalence of dyspnea (OR = 0.84 and 0.80, respectively) but not with chronic bronchitis. The results indicate no benefit from supplementation with alpha-tocopherol or beta-carotene on the symptoms of chronic obstructive pulmonary disorders but support the beneficial effect of dietary intake of fruits and vegetables rich in these compounds.     

Plasma free tryptophan variation during oestrous cycle of the rat

The concentration of plasma free tryptophan was shown to undergo a regular and statistically significant fluctuation through the four phases of the oestrous cycle of the rat. The highest concentration of plasma free tryptophan was observed during oestrus. During metoestrus the concentration of plasma free tryptophan decreased by 25% to the lowest observed level; thereafter it gradually increased during dioestrus and pro-oestrus. The concentration of plasma total tryptophan was found to be unchanged during the oestrous cycle of the rat.     

A full-wave Helmholtz model for continuous-wave ultrasound transmission

A full-wave Helmholtz model of continuous-wave (CW) ultrasound fields may offer several attractive features over widely used partial-wave approximations. For example, many full-wave techniques can be easily adjusted for complex geometries, and multiple reflections of sound are automatically taken into account in the model. To date, however, the full-wave modeling of CW fields in general 3D geometries has been avoided due to the large computational cost associated with the numerical approximation of the Helmholtz equation. Recent developments in computing capacity together with improvements in finite element type modeling techniques are making possible wave simulations in 3D geometries which reach over tens of wavelengths. The aim of this study is to investigate the feasibility of a full-wave solution of the 3D Helmholtz equation for modeling of continuous-wave ultrasound fields in an inhomogeneous medium. The numerical approximation of the Helmholtz equation is computed using the ultraweak variational formulation (UWVF) method. In addition, an inverse problem technique is utilized to reconstruct the velocity distribution on the transducer which is used to model the sound source in the UWVF scheme. The modeling method is verified by comparing simulated and measured fields in the case of transmission of 531 kHz CW fields through layered plastic plates. The comparison shows a reasonable agreement between simulations and measurements at low angles of incidence but, due to mode conversion, the Helmholtz model becomes insufficient for simulating ultrasound fields in plates at large angles of incidence.     

Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP)

Efflux transporters, namely ATP-binding cassette (ABC), are one of the primary reasons for cancer chemoresistance and the clinical failure of chemotherapy. Ganciclovir (GCV) is an antiviral agent used in herpes simplex virus thymidine kinase (HSV-TK) gene therapy. In this therapy, HSV-TK gene is delivered together with GCV into cancer cells to activate the phosphorylation process of GCV to active GCV-triphosphate, a DNA polymerase inhibitor. However, GCV interacts with efflux transporters that are responsible for the resistance of HSV-TK/GCV therapy. In the present study, it was explored whether GCV and its more lipophilic derivative (1) could inhibit effluxing of another chemotherapeutic, methotrexate (MTX), out of the human breast cancer cells. Firstly, it was found that the combination of GCV and MTX was more hemocompatible than the corresponding combination with compound 1. Secondly, both GCV and compound 1 enhanced the cellular accumulation of MTX in MCF-7 cells, the MTX exposure being 13–21 times greater compared to the MTX uptake alone. Subsequently, this also reduced the number of viable cells (41–56%) and increased the number of late apoptotic cells (46–55%). Moreover, both GCV and compound 1 were found to interact with breast cancer resistant protein (BCRP) more effectively than multidrug-resistant proteins (MRPs) in these cells. Since the expression of BCRP was higher in MCF-7 cells than in MDA-MB-231 cells, and the cellular uptake of GCV and compound 1 was smaller but increased in the presence of BCRP-selective inhibitor (Fumitremorgin C) in MCF-7 cells, we concluded that the improved apoptotic effects of higher MTX exposure were raised mainly from the inhibition of BCRP-mediated efflux of MTX. However, the effects of GCV and its derivatives on MTX metabolism and the quantitative expression of MTX metabolizing enzymes in various cancer cells need to be studied more thoroughly in the future.     

Genome-Wide Identification and Characterization of PIN-FORMED (PIN) Gene Family Reveals Role in Developmental and Various Stress Conditions in Triticum aestivum L.

PIN-FORMED (PIN) genes play a crucial role in regulating polar auxin distribution in diverse developmental processes, including tropic responses, embryogenesis, tissue differentiation, and organogenesis. However, the role of PIN-mediated auxin transport in various plant species is poorly understood. Currently, no information is available about this gene family in wheat (Triticum aestivum L.). In the present investigation, we identified the PIN gene family in wheat to understand the evolution of PIN-mediated auxin transport and its role in various developmental processes and under different biotic and abiotic stress conditions. In this study, we performed genome-wide analysis of the PIN gene family in common wheat and identified 44 TaPIN genes through a homology search, further characterizing them to understand their structure, function, and distribution across various tissues. Phylogenetic analyses led to the classification of TaPIN genes into seven different groups, providing evidence of an evolutionary relationship with Arabidopsis thaliana and Oryza sativa. A gene exon/intron structure analysis showed a distinct evolutionary path and predicted the possible gene duplication events. Further, the physical and biochemical properties, conserved motifs, chromosomal, subcellular localization, transmembrane domains, and three-dimensional (3D) structure were also examined using various computational approaches. Cis-elements analysis of TaPIN genes showed that TaPIN promoters consist of phytohormone, plant growth and development, and stress-related cis-elements. In addition, expression profile analysis also revealed that the expression patterns of the TaPIN genes were different in different tissues and developmental stages. Several members of the TaPIN family were induced during biotic and abiotic stress. Moreover, the expression patterns of TaPIN genes were verified by qRT-PCR. The qRT-PCR results also show a similar expression with slight variation. Therefore, the outcome of this study provides basic genomic information on the expression of the TaPIN gene family and will pave the way for dissecting the precise role of TaPINs in plant developmental processes and different stress conditions.     

Oxidative capacity and hemolytic activity of settled dust from moisture‐damaged schools

Exposure to moisture‐damaged indoor environments is associated with adverse respiratory health effects, but responsible factors remain unidentified. In order to explore possible mechanisms behind these effects, the oxidative capacity and hemolytic activity of settled dust samples (n = 25) collected from moisture‐damaged and non‐damaged schools in Spain, the Netherlands, and Finland were evaluated and matched against the microbial content of the sample. Oxidative capacity was determined with plasmid scission assay and hemolytic activity by assessing the damage to isolated human red blood cells. The microbial content of the samples was measured with quantitative PCR assays for selected microbial groups and by analyzing the cell wall markers ergosterol, muramic acid, endotoxins, and glucans. The moisture observations in the schools were associated with some of the microbial components in the dust, and microbial determinants grouped together increased the oxidative capacity. Oxidative capacity was also affected by particle concentration and country of origin. Two out of 14 studied dust samples from moisture‐damaged schools demonstrated some hemolytic activity. The results indicate that the microbial component connected with moisture damage is associated with increased oxidative stress and that hemolysis should be studied further as one possible mechanism contributing to the adverse health effects of moisture‐damaged buildings.     

Cyp1 Inhibition Prevents Doxorubicin-Induced Cardiomyopathy in a Zebrafish Heart-Failure Model

Doxorubicin is a highly effective chemotherapy agent used to treat many common malignancies. However, its use is limited by cardiotoxicity, and cumulative doses exponentially increase the risk of heart failure. To identify novel heart failure treatment targets, a zebrafish model of doxorubicin-induced cardiomyopathy was previously established for small-molecule screening. Using this model, several small molecules that prevent doxorubicin-induced cardiotoxicity both in zebrafish and in mouse models have previously been identified. In this study, exploration of doxorubicin cardiotoxicity is expanded by screening 2271 small molecules from a proprietary, target-annotated tool compound collection. It is found that 120 small molecules can prevent doxorubicin-induced cardiotoxicity, including 7 highly effective compounds. Of these, all seven exhibited inhibitory activity towards cytochrome P450 family 1 (CYP1). These results are consistent with previous findings, in which visnagin, a CYP1 inhibitor, also prevents doxorubicin-induced cardiotoxicity. Importantly, genetic mutation of cyp1a protected zebrafish against doxorubicin-induced cardiotoxicity phenotypes. Together, these results provide strong evidence that CYP1 is an important contributor to doxorubicin-induced cardiotoxicity and highlight the CYP1 pathway as a candidate therapeutic target for clinical cardioprotection.     

High-sensitivity detection of triacetone triperoxide (TATP) and its precursor acetone

Triacetone triperoxide (C(9)H(18)O(6), molecular mass of 222.24 g/mol) (TATP) is a powerful explosive that is easy to synthesize using commonly available household chemicals, acetone, and hydrogen peroxide 1 2. Because of the simplicity of its synthesis, TATP is often the explosive of choice for terrorists, including suicide bombers. For providing safety to the population, early detection of TATP and isolation of such individuals are essential. We report unambiguous, high-sensitivity detection of TATP and its precursor, acetone, using room-temperature quantum cascade laser photoacoustic spectroscopy (QCL-PAS). The available sensitivity is such that TATP, carried on a person (at a nominal body temperature of 37 degrees C), should be detectable at some distance. The combination of demonstrated detection of TATP and acetone should be ideal for screening at airports and other public places for providing increased public safety.