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Oxidative stress and neuronal death are the primary reasons for the progression of amyloid-beta (Aβ) deposition and cognitive deficits in Alzheimer's disease (AD). Ecdysterone (ecdy), a common derivative of ecdysteroids, possesses free radical scavenging and cognitive-improving effects. High-intensity interval training (HIIT) can be a therapeutic strategy for improving cognitive decline and oxidative stress. The present study was aimed to evaluate the effect of HIIT exercise and ecdy consumption synergistically on the changes in learning and memory functions, activities of hippocampal antioxidant enzymes, and neuronal population after AD induced by Aβ in male rats.

Following ten days of Aβ injection, HIIT exercise and ecdy treatment (10mg/kg/day; P.O.) were initiated and continued for eight consecutive weeks in rats. At the end of the treatment period, the rat's learning and memory functions were assessed using Morris water maze and passive avoidance tests. The activity of superoxide dismutase (SOD), catation of HIIT and ecdy treatment could be a promising potential therapeutic option against AD-associated cognitive decline, owing to their free radical scavenging and neuroprotective properties.The digit ratio (2D4D) is a negative correlate of boy's physical fitness, and thought to arise from organizational effects of prenatal testosterone on different bodily systems. During human ontogeny, activational effects of testosterone on body size and strength offers another pathway to physical fitness. We tested these hypotheses by examining the organizational and activational effects of testosterone on vertical jump performance in athletic boys. Using a cross-sectional design, 173 boys (aged 9 to 18 years) were tested for standing height, body mass, body fat, fat-free mass, weekly training activity, training history, salivary testosterone and cortisol, R2D4D, L2D4D, and right-left 2D4D (Dr-1), and vertical height in 3 different countermovement jump (CMJ) tests. A generalized additive model was employed to delineate age-related trajectories and predict CMJ performance. Our models yielded significant non-linear increases (or changes) in body size, current hormone concentration, training outcomes, and CMJ performance with chronological age. All 2D4D measures were age invariant. The R2D4D and testosterone were significant non-linear predictors of CMJ height with (R2 = 66.2%) or without (R2 = 54.3%) covariates, whereby a higher current testosterone concentration (up to a certain level) and a lower or higher R2D4D were linked to better performance. The L2D4D and Dr-1 had no predictive value. In conclusion, the R2D4D and testosterone were co-predictors of CMJ height among athletic boys, with non-linear performance effects that differed in timing, tempo, and direction. Our findings confirm that testosterone can regulate a simple measure of boy's physical fitness through both an activational and organizational pathway.Reptiles have become popular exotic pets and in some parts of the world, they are used as important source of food, medicines, and materials. Synanthropic lizards are recognized as reservoirs of viruses, bacteria, and parasites but their role in dissemination of zoonotic pathogenic yeasts in the environment was never investigated. Therefore, fecal samples (n=177) from Podarcis siculus (Italian wall lizard), Chalcides ocellatus (Ocellated skink) and Tarentola mauritanica (Moorish gecko) were collected and yeasts were isolated and identified biochemically and molecularly by sequencing the rDNA internal transcribed spacer region (ITS). The phylogenetical relationship of isolated yeast species and their antifungal susceptibility profiles to ten antifungal agents were also assessed. Sixty samples (n=60/177; 33.9%) scored positive for yeasts, with the highest occurrence in C. ocellatus (n=11/17; 64.7%) and the highest variety of species in P. siculus (n=11/12; 91.6%). A total of 364 isolates belonging to Candida, Trichosporon, Saccharomyces and Geotrichum genera were molecularly identified. In particular, Candida albicans (n=160; 44%) followed by Trichosporon coremiiforme (n=44; 12.1%), Pichia kudriavzevii (n=32; 8.8%) and Trichosporon asahii (n=28; 7.7%) were the most frequently isolated species. The phylogenetic tree grouped all representative sequence types within the clade including Candida spp. strains from different geographical areas and from animal species, including human. All tested strains showed high susceptibility to the assayed antifungal drugs. This study suggests the role of lizards as reservoirs and spreaders of zoonotic pathogenic yeasts in the environment. The absence of resistance phenomena in the isolated yeasts might reflect an environment free of azole antifungal pollution or chemicals, suggesting the usefulness of these animals as bio indicators of environment quality.Breeding snakes in captivity has become more and more relevant due not only to the growing interest on their venoms but also to the increasing number of endangered species worldwide. Unfortunately, studies on the formation of germplasm banks for these reptiles do not follow the same pace, and literature on sperm cryopreservation remains in its infancy when compared to other taxa. Herein, we first validated a sperm-egg binding assay (using chicken egg perivitelline membrane - EPM) and some nonfluorescent staining techniques for semen analysis of two pit viper genera (Bothrops and Crotalus), and then we investigated the protective effects of dimethylacetamide (DMA), dimethylformamide (DMF), and dimethylsulfoxide (DMSO) at different concentrations (3, 6 and 12%) throughout the freezing process in five species of lancehead and one of rattlesnake. Our validation process showed high correlations among sperm functional tests (including sperm-binding to EPM) and motion parameters. A total of 166 fresh ejaculates were acquired from 233 collection attempts, and 63.9% of these samples exhibited minimal motility for freezing (≥20%). During cryopreservation we observed that post-thaw motility and quality was improved by higher levels of cryoprotectants (CPA), regardless the CPA type. Lower concentrations of CPA were less harmful to sperm motility and progressive motility following the equilibrium phase, but were ineffective in protecting these cells from the freeze-thaw cycle. Likewise, higher CPA concentrations increased post-thaw integrity of the acrosome and plasma membrane for most species, except for rattlesnakes in which only 12% DMSO produced better outcomes.

in patients with heart failure (HF) and atrial fibrillation (AF), AF ablation improves left ventricular ejection fraction (LVEF), along with prognosis, in a variable percentage of patients. We aimed to investigate the predictors of LVEF recovery after AF ablation and to develop a prediction model for individualized assessment.

we conducted an observational, retrospective, single-centre study on 111 consecutive patients with AF and HF with impaired LVEF (<50%) undergoing ablation. Patients were divided into Responder vs. Non-Responder according to the "Universal definition of HF". Clinical predictors were evaluated by multivariate logistic regression analysis and cross-validation technique. Independent predictors were used to build an internally validated prediction model.

Responders (54%) had significantly shorter QRS duration and less dilated left atrium. Persistent AF and absence of a known etiology were more frequent among Responders. AF recurrence was similar between the two groups (p=0.2), but tprospective validation.Opioid receptor agonists are effective analgesic agents. Central activation of the mu and/or kappa opioid receptors (KOR) is associated with CNS side effects, which limits their effectiveness. Recent studies indicated that peripherally restricted, selective KOR agonists were potent analgesics and devoid of CNS-related side effects. To confirm this hypothesis, we designed a novel, potent, and peripherally restricted KOR-selective agonist, ZYKR1. The analgesic efficacy, brain penetration and safety of ZYKR1 were assessed in pre-clinical models. ZYKR1 showed KOR agonistic activity in the cAMP assay, with an EC50 of 0.061 nM and more than 105-fold selectivity over the mu and delta opioid receptors (EC50 > 10 μM). ZYKR1 was not found to bind mu, delta opioid, and NOP receptors in radioligand binding assays. ZYKR1 produced concentration-dependent inhibition of electrically evoked contractions in isolated mouse vas deferens with an IC50 of 1.6 nM ZYKR1 showed peripheral restriction and potent analgesic efficacy in various in-vivo animal models (acetic acid induced visceral pain mouse model, ED50 0.025 mg/kg, IV; ovariohysterectomy induced postoperative pain rat model, ED50 0.023 mg/kg, IV; and C48/80 induced pruritus mouse model, ED50 0.063 mg/kg, IV). In addition, ZYKR1 was devoid of motor coordination, physical dependence, dysphoria, and respiratory depression at 30, 400, 10 and 10-fold of efficacy dose, respectively. In conclusion, ZYKR1 has potent antinociceptive action in visceral pain and pruritus with limited CNS side effects in preclinical models owing to its peripheral restriction.Amanitin poisoning still has no particular, effective antidote. Erdosteine has been shown to protect numerous tissues, particularly those in the liver. This study investigates the potential therapeutic effects of erdosteine on alpha-, beta- and gamma-amanitin-induced hepatotoxicity in in vitro models. Three hours after administering amatoxins at various concentrations (1-50 μg/mL) to the cells of the C3A human hepatocyte cell line, erdosteine was administered in different concentrations (i.e., 1, 10, 50, 100 and 250 μg/mL). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was selected to determine cell viability. When concentrations of 1, 10, 50, 100 and 250 μg/mL of erdosteine were applied to cell lines, the following cell viability rates were obtained 106%,99%,93%,86% and 86%, respectively, at a 10 μg/mL alpha-amanitin-induced toxicity; 43%,41%,41%,37% and 35%, respectively, at a 25 μg/mL alpha-amanitin-induced toxicity; 44%,42%,41%,39% and 41%, respectively, at a 50 μg/mL alpha-amanitin-induced toxicity; 136%,142%,143%,137% and 120%, respectively, at a 10 μg/mL beta-amanitin-induced toxicity; 113%,107%,107%,106% and 86%, respectively, at a 25 μg/mL beta-amanitin-induced toxicity; 78%,77%,77%,74% and 70%, respectively, at a 10 μg/mL gamma-amanitin-induced toxicity; and 39%,40%,39%,35% and 31%, respectively, at a 25 μg/mL gamma-amanitin-induced toxicity. This study was the first to evaluate the in vitro efficacy of erdosteine in cytotoxicity induced by alpha-, beta- and gamma-amanitin. Non-high (low and medium) doses of erdosteine are capable of nearly entirely preventing toxicity at mild hepatotoxic concentrations caused by amatoxin and partially preventing toxicity at moderate and severe concentrations. The beneficial effects of erdosteine, especially on the toxicity of alpha- and beta-amanitin, are promising.Developmental biology has contributed greatly to evolutionary biology in the past century. With the discovery that vertebrates share Hox genes with Drosophila in 1984, it became apparent that all animals evolved from variations of an ancestral embryonic patterning genetic tool-kit. In the dorsal-ventral (D-V) axis, a fundamental experiment was the Spemann-Mangold organizer transplant performed in 1924. Almost a century later, D-V genes have been subjected to saturating molecular screens in Xenopus and extensive genetic screens in zebrafish. A network of secreted growth factor antagonists has emerged, and we review here in detail the Chordin/Tolloid/BMP pathway. Chordin establishes a morphogen gradient spanning the entire embryo that was present even in the cnidarian Nematostella. This ancient system was present in Urbilateria, the last common ancestor of the protostome and deuterostome bilateral animals. Colivelin mouse We suggest that Urbilateria had a complex life cycle with an adult benthic form on the sea bottom, and also a primary larval pelagic or planktonic phase to disperse the species in the marine milieu.

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