Activity

  • Enevoldsen Foldager posted an update 4 months, 3 weeks ago

    The search for new formulations for transdermal drug delivery (TDD) is an important field in medicine and cosmetology. Molecules with specific physicochemical properties which can increase the permeability of active ingredients across the stratum corneum (SC) are called chemical penetration enhancers (CPEs), and it was shown that some CPEs can act synergistically. In this study, we performed coarse-grained (CG) molecular dynamics (MD) simulations of the lidocaine delivery facilitated by two CPEs-linoleic acid (LA) and ethanol-through the SC model membrane containing cholesterol, N-Stearoylsphingosine (DCPE), and behenic acid. In our simulations, we probed the effects of individual CPEs as well as their combination on various properties of the SC membrane and the lidocaine penetration across it. We demonstrated that the addition of both CPEs decreases the membrane thickness and the order parameters of the DPCE hydrocarbon chains. Moreover, LA also enhances diffusion of the SC membrane components, especially cholesterol. The estimated potential of mean force (PMF) profiles for the lidocaine translocation across SC in the presence/absence of two individual CPEs and their combination demonstrated that while ethanol lowers the free energy barrier for lidocaine to enter SC, LA decreases the depth of the free energy minima for lidocaine inside SC. These two effects supposedly result in synergistic penetration enhancement of drugs. Altogether, the present simulations provide a detailed molecular picture of CPEs’ action and their synergistic effect on the penetration of small molecular weight therapeutics that can be beneficial for the design of novel drug and cosmetics formulations.Three edible mushroom species (Imlera badia, Boletus subtomentosus, Xerocomellus chrysenteron) sampled in 60 different localities of Slovakia were evaluated to determine health risks (associated with mercury content) arising from their consumption. buy FX11 Total content of mercury in soil and mushroom samples was determined by an AMA-254 analyzer. Soil pollution by mercury was evaluated by contamination factor (Cf), pollution load index (PLI), and geoaccumulation index (Igeo). Bioaccumulation factor (BAF), translocation factor (Qc/s), provisional tolerably weekly intake (%PTWI), estimated daily intake (EDI), and target hazard quotient (THQ) were used to describe and compare uptake and transition abilities of mushrooms, and the health risk arising from mushroom consumption. Mercury content in soil significantly influences the content of mercury in mushroom fruiting body parts. Caps and stipes of Boletus subtomentosus were found to be the best mercury accumulator. According to the EDI, consumption of the evaluated mushroom species represents a serious threat for adults and children. The lowest values of THQ were found for Xerocomellus chysenteron.Recent research has shown that good sleep quality has a positive effect on physical performance. However, sleep quality in Chilean professional soccer players is unknown. The purpose of this study was to determine sleep quality in Chilean professional soccer players. It was a cross-sectional, explanatory study with observable variables. The sample consisted of 94 Chilean male soccer players belonging to four professional clubs. The main variable was the Sleep Quality Index, evaluated through the Pittsburgh questionnaire (Spanish version). After estimating sleep quality individually, the four professional soccer clubs’ comparison was performed through a one-factor ANOVA. The Pearson test was used to relate the questionnaire variables; the significance level was p 0.05). Based on the results obtained, Chilean male professional soccer players present good sleep quality. However, the high values of “sleep latency” and “sleep disturbances” are indicators that should be worked on by the multidisciplinary team of each professional club. They should develop strategies to improve sleep hygiene, encourage good sleep, and fall asleep efficiently.Cassava is one of the most important staple crops in Africa and its production is seriously damaged by viral diseases. In this study, we identify for the first time and characterize the genome organization of novel ampeloviruses infecting cassava plants in diverse geographical locations using three high-throughput sequencing protocols [Virion-Associated Nucleotide Acid (VANA), dsRNA and total RNA], and we provide a first analysis of the diversity of these agents and of the evolutionary forces acting on them. Thirteen new Closteroviridae isolates were characterized in field-grown cassava plants from the Democratic Republic of Congo (DR Congo), Madagascar, Mayotte, and Reunion islands. The analysis of the sequences of the corresponding contigs (ranging between 10,417 and 13,752 nucleotides in length) revealed seven open reading frames. The replication-associated polyproteins have three expected functional domains methyltransferase, helicase, and RNA-dependent RNA polymerase (RdRp). Additional open reading frames code for a small transmembrane protein, a heat-shock protein 70 homolog (HSP70h), a heat shock protein 90 homolog (HSP90h), and a major and a minor coat protein (CP and CPd respectively). Defective genomic variants were also identified in some cassava accessions originating from Madagascar and Reunion. The isolates were found to belong to two species tentatively named Manihot esculenta-associated virus 1 and 2 (MEaV-1 and MEaV-2). Phylogenetic analyses showed that MEaV-1 and MEaV-2 belong to the genus Ampelovirus, in particular to its subgroup II. MEaV-1 was found in all of the countries of study, while MEaV-2 was only detected in Madagascar and Mayotte. Recombination analysis provided evidence of intraspecies recombination occurring between the isolates from Madagascar and Mayotte. No clear association with visual symptoms in the cassava host could be identified.Genomic alterations and aberrant DNA damage signaling are hallmarks of ovarian cancer (OC), the leading cause of mortality among gynecological cancers worldwide. Owing to the lack of specific symptoms and late-stage diagnosis, survival chances of patients are significantly reduced. Poly (ADP-ribose) polymerase (PARP) inhibitors and replication stress response inhibitors present attractive therapeutic strategies for OC. Recent research has focused on ovarian cancer-associated microRNAs (miRNAs) that play significant regulatory roles in various cellular processes. While miRNAs have been shown to participate in regulation of tumorigenesis and drug responses through modulating the DNA damage response (DDR), little is known about their potential influence on sensitivity to chemotherapy. The main objective of this review is to summarize recent findings on the utility of miRNAs as cancer biomarkers, in particular, ovarian cancer, and their regulation of DDR or modified replication stress response proteins. We further discuss the suppressive and promotional effects of various miRNAs on ovarian cancer and their participation in cell cycle disturbance, response to DNA damage, and therapeutic functions in multiple cancer types, with particular focus on ovarian cancer.