Cardioprotective Diet to Prevent Anthracycline-Induced Cardiotoxicity in Patients with Breast Cancer: A Randomized Open-Label Controlled Trial.

Objectives: Several studies have indicated that dietary interventions may offer protection against the development of cardiac damage in the case of anthracycline-induced cardiomyopathy (AIC). The goal of this study was to assess whether an evidence-based cardioprotective diet can be effective in preventing AIC in patients with breast cancer. Design: Randomized, open-label, controlled trial. The study period was set for 18 weeks, and the data were analyzed by generalized estimating equation modeling and one-way repeated measures analysis of variance. Setting/Location: Shahid Rajaie Hospital affiliated (Tehran, Iran). Subjects: Fifty anthracycline-treated patients with breast cancer. Interventions: Patients were randomized to receive either a 2-hour training in evidence-based cardio-protective diet or Carvedilol 6.25 mg bid. Outcome Measures: The primary outcome was the number of patients with abnormal left ventricular ejection fraction (LVEF) after 18 weeks. Results: At week 18, 12 (48%) out of 25 participants in the cardioprotective diet group had abnormal LVEF in comparison with 21 (84%) out of 25 in the carvedilol group (p = 0.007). Also, 2 (8%) out of 25 in the cardioprotective diet group compared with 7 (28%) out of 25 participants in the carvedilol group had abnormal global longitudinal strain (p = 0.066). The diet group showed significant improvements in the quality-of-life dimensions named "health change" and "general health" compared with the carvedilol group using the Short Form-36 Health Survey questionnaire. Conclusions: This study suggests that an evidence-based cardioprotective diet can contribute to the prevention of AIC. Although current treatments for AIC can be effective, further research is mandatory for more options.

Bending Unwinds DNA.

In biology, DNA is often tightly bent to small radii. Solely based on the groove asymmetry, a 30-year-old theoretical paper predicted that such bending should unwind DNA, but this effect has not been directly experimentally quantified so far. We developed a ligation-based assay with nicked DNA circles of variable length, thereby decoupling the twist-dependent ligation efficiency from the large bending strain which dominates conventional circularization assays. We demonstrate that tightly bent DNA indeed unwinds to over 11 base pairs/turn, exactly as predicted. Our discovery requires reassessing the molecular mechanisms and energetics of all processes where DNA is tightly bent or relaxed again, including DNA packaging, gene regulation and expression.

Local and cooperative structural transitions of double-stranded DNA in choline-based deep eutectic solvents.

The possibility of using deep eutectic solvents (DESs) as co-solvents for stabilizing and preserving the native structure of DNA provides an attractive opportunity in the field of DNA biotechnology. The rationale of this work is a systematic investigation of the effect of hydrated choline-based DES on the structural stability of a 30-base-pair double-stranded DNA model via a combination of spectroscopic experiments and MD simulations. UV absorption and CD experiments provide evidence of a significant contribution of DESs to the stabilization of the double-stranded canonical (B-form) DNA structure. Multi-wavelength synchrotron UV Resonance Raman (UVRR) measurements indicate that the hydration shell of adenine-thymine pairs is strongly perturbed in the presence of DESs and that the preferential interaction between H-bond sites of guanine residues and DESs is significantly involved in the stabilization of the dsDNA. Finally, MD calculations show that the minor groove of DNA is significantly selective for the choline part of the investigated DESs compared to the major groove. This finding is likely to have a significant impact not only in terms of thermal stability but also in the modulation of ligand-DNA interactions.

Modulation of global stability, ligand binding and catalytic properties of trypsin by anions.

Specific salts effect is well-known on stability and solubility of proteins, however, relatively limited knowledge is known regarding the effect on catalytic properties of enzymes. Here, we examined the effect of four sodium anions on thermal stability and catalytic properties of trypsin and binding of the fluorescent probe, p-aminobenzamidine (PAB), to the enzyme. We show that the specific anions effect on trypsin properties agrees with the localization of the anions in the Hofmeister series. Thermal stability of trypsin, Tm, the affinity of the fluorescent probe to the binding site, Kd, and the rate constant, kcat, of trypsin-catalyzed hydrolysis of the substrate N-benzoyl-L-arginine ethyl ester (BAEE) increase with increasing kosmotropic character of anions in the order: perchlorate

Specific anion effect on properties of HRV 3C protease.

Specific salts effect is intensively studied from the prospective of modification of different physico-chemical properties of biomacromolecules. Limited knowledge of the specific salts effect on enzymes led us to address the influence of five sodium anions: sulfate, phosphate, chloride, bromide, and perchlorate, on catalytic and conformational properties of human rhinovirus-14 (HRV) 3C protease. The enzyme conformation was monitored by circular dichroism spectrum (CD) and by tyrosines fluorescence. Stability and flexibility of the enzyme have been analyzed by CD in the far-UV region, differential scanning calorimetry and molecular dynamics simulations, respectively. We showed significant influence of the anions on the enzyme properties in accordance with the Hofmeister effect. The HRV 3C protease in the presence of kosmotropic anions, in contrast with chaotropic anions, exhibits increased stability, rigidity. Correlations of stabilization effect of anions on the enzyme with their charge density and the rate constant of the enzyme with the viscosity B-coefficients of anions suggest direct interaction of the anions with HRV 3C protease. The role of stabilization and decreased fluctuation of the polypeptide chain of HRV 3C protease on its activation in the presence of kosmotropic anions is discussed within the frame of the macromolecular rate theory.

Interactions between a dsDNA Oligonucleotide and Imidazolium Chloride Ionic Liquids: Effect of Alkyl Chain Length, Part I.

Ionic liquids (ILs) have become nearly ubiquitous solvents and their interactions with biomolecules has been a focus of study. Here, we used the fluorescence emission of DAPI, a groove binding fluorophore, coupled with molecular dynamics (MD) simulations to report on interactions between imidazolium chloride ([Imn,1]+) ionic liquids and a synthetic DNA oligonucleotide composed entirely of T/A bases (7(TA)) to elucidate the effects ILs on a model DNA duplex. Spectral shifts on the order of 500-1000 cm-1, spectral broadening (~1000 cm-1), and excitation and emission intensity ratio changes combine to give evidence of an increased DAPI environment heterogeneity on added IL. Fluorescence lifetimes for DAPI/IL solutions yielded two time constants 0.15 ns (~80% to 60% contribution) and 2.36-2.71 ns for IL up to 250 mM. With DNA, three time constants were required that varied with added IL (0.33-0.15 ns (1-58% contribution), ~1.7-1.0 ns (~5% contribution), and 3.8-3.6 ns (94-39% contribution)). MD radial distribution functions revealed that π-π stacking interactions between the imidazolium ring were dominant at lower IL concentration and that electrostatic and hydrophobic interactions become more prominent as IL concentration increased. Alkyl chain alignment with DNA and IL-IL interactions also varied with IL. Collectively, our data showed that, at low IL concentration, IL was primarily bound to the DNA minor groove and with increased IL concentration the phosphate regions and major groove binding sites were also important contributors to the complete set of IL-DNA duplex interactions.

Surface Interaction of Ionic Liquids: Stabilization of Polyethylene Terephthalate-Degrading Enzymes in Solution.

The effect of aqueous solutions of selected ionic liquids solutions on Ideonella sakaiensis PETase with bis(2-hydroxyethyl) terephthalate (BHET) substrate were studied by means of molecular dynamics simulations in order to identify the possible effect of ionic liquids on the structure and dynamics of enzymatic Polyethylene terephthalate (PET) hydrolysis. The use of specific ionic liquids can potentially enhance the enzymatic hydrolyses of PET where these ionic liquids are known to partially dissolve PET. The aqueous solution of cholinium phosphate were found to have the smallest effect of the structure of PETase, and its interaction with (BHET) as substrate was comparable to that with the pure water. Thus, the cholinium phosphate was identified as possible candidate as ionic liquid co-solvent to study the enzymatic hydrolyses of PET.

The ability of mouse nuclear transfer embryonic stem cells to differentiate into primordial germ cells.

Nuclear transfer embryonic stem cells (ntESCs) show stem cell characteristics such as pluripotency but cause no immunological disorders. Although ntESCs are able to differentiate into somatic cells, the ability of ntESCs to differentiate into primordial germ cells (PGCs) has not been examined. In this work, we examined the capacity of mouse ntESCs to differentiate into PGCs in vitro. ntESCs aggregated to form embryoid bodies (EB) in EB culture medium supplemented with bone morphogenetic protein 4(BMP4) as the differentiation factor. The expression level of specific PGC genes was compared at days 4 and 8 using real time PCR. Flow cytometry and immunocytochemical staining were used to detect Mvh as a specific PGC marker. ntESCs expressed particular genes related to different stages of PGC development. Flow cytometry and immunocytochemical staining confirmed the presence of Mvh protein in a small number of cells. There were significant differences between cells that differentiated into PGCs in the group treated with Bmp4 compared to non-treated cells. These findings indicate that ntESCs can differentiate into putative PGCs. Improvement of ntESC differentiation into PGCs may be a reliable means of producing mature germ cells.