Andiroba (Carapa guianensis) seeds are the source of an oil with a wide range of biological activities and ethnopharmacological uses. However, few studies have devoted attention to innovative ...formulations, including nanoemulsions. The present study aimed to obtain a colloidal system with the andiroba oil using a low-energy and organic-solvent-free method. Moreover, the preliminary residual larvicidal activity of the nanoemulsion against Aedes aegypti was evaluated. Oleic and palmitic acids were the major fatty acids, in addition to the phytosterol β-sitosterol and limonoids (tetranortriterpenoids). The required hydrophile-lipophile was around 11.0 and the optimal nanoemulsion was obtained using polysorbate 85. The particle size distribution suggested the presence of small droplets (mean diameter around 150 nm) and low polydispersity index (around 0.150). The effect of temperature on particle size distribution revealed that no major droplet size increase occurred. The preliminary residual larvicidal assay suggested that the mortality increased as a function of time. The present study allowed achievement of a potential bioactive oil in water nanoemulsion that may be a promising controlled release system. Moreover, the ecofriendly approach involved in the preparation associated with the great bioactive potential of C. guianensis makes this nanoemulsion very promising for valorization of this Amazon raw material.
BACKGROUND The impact of OSA on new cardiovascular events in patients undergoing coronary artery bypass graft (CABG) surgery is poorly explored. METHODS Consecutive patients referred for CABG ...underwent clinical evaluation and standard polysomnography in the preoperative period. CABG surgery data, including percentage of off-pump and on-pump CABG, number of grafts, and intraoperative complications, were collected. The primary end point was major adverse cardiac or cerebrovascular events (MACCEs) (combined events of all-cause death, myocardial infarction, repeated revascularization, and cerebrovascular events). Secondary end points included individual MACCEs, typical angina, and arrhythmias. Patients were evaluated at 30 days (short-term) and up to 6.1 years (long term) after CABG. RESULTS We studied 67 patients (50 men; mean age, 58 ± 8 years; mean BMI, 28.5 ± 4.1 kg/m2 ). OSA (apnea-hypopnea index ≥ 15 events/h) was present in 56% of the population. The patients were followed for a mean of 4.5 years (range, 3.2-6.1 years). No differences were observed in the short-term follow-up. In contrast, MACCE (35% vs 16%, P = .02), new revascularization (19% vs 0%, P = .01), episodes of typical angina (30% vs 7%, P = .02), and atrial fibrillation (22% vs 0%, P = .0068) were more common in patients with than without OSA in the long-term follow-up. OSA was an independent factor associated with the occurrence of MACCE, repeated revascularization, typical angina, and atrial fibrillation in the multivariate analysis. CONCLUSIONS OSA is independently associated with a higher rate of long-term cardiovascular events after CABG and may have prognostic and economic significance in CABG surgery.
In humans, the combination of all sex-specific genetic, epigenetic, and hormonal influences of biologic sex produces different in vivo environments for male and female cells. We dissect how these ...influences of sex modify the pharmacokinetics and pharmacodynamics of multiple drugs and provide examples for common drugs acting on specific organ systems. We also discuss how gender of physicians and patients may influence the therapeutic response to drugs. We aim to highlight sex as a genetic modifier of the pharmacological response to drugs, which should be considered as a necessary step toward precision medicine that will benefit men and women. SIGNIFICANCE STATEMENT: This study discusses the influences of biologic sex on the pharmacokinetics and pharmacodynamics of drugs and provides examples for common drugs acting on specific organ systems. This study also discusses how gender of physicians and patients influence the therapeutic response to drugs.
Brazil is one of the countries that experienced an epidemic of microcephaly and other congenital manifestations related to maternal Zika virus infection which can result in Congenital Zika Syndrome ...(CZS). Since the Zika virus can modulate the immune system, studying mothers' and children's immune profiles become essential to better understanding CZS development. Therefore, we investigated the lymphocyte population profile of children who developed CZS and their mothers' immune response in this study. The study groups were formed from the Plaque Reduction Neutralization Test (PRNT) (CZS+ group) result. To evaluate the lymphocyte population profile, we performed phenotyping of peripheral lymphocytes and quantification of serum cytokine levels. The immunophenotyping and cytokine profile was correlated between CSZ+ children and their mothers. Both groups exhibited increased interleukin-17 levels and a reduction in the subpopulation of CD4+ T lymphocytes. In contrast, the maternal group showed a reduction in the population of B lymphocytes. Thus, the development of CZS is related to the presence of an inflammatory immune profile in children and their mothers characterized by Th17 activation.
Understanding gaps in academic representation while considering the intersectionality concept is paramount to promoting real progress towards a more inclusive STEM. Here we discuss ways in which STEM ...careers can be sown and germinated so that inclusivity can flourish.
The cardiac circadian clock is responsible for the modulation of different myocardial processes, and its dysregulation has been linked to disease development. How this clock machinery is regulated in ...the heart remains an open question. Because noradrenaline (NE) can act as a zeitgeber in cardiomyocytes, we tested the hypothesis that adrenergic signaling resets cardiac clock gene expression in vivo. In its anti‐phase with Clock and Bmal1, cardiac Per1 abundance increased during the dark phase, concurrent with the rise in heart rate and preceded by an increase in NE levels. Sympathetic denervation altered Bmal1 and Clock amplitude, while Per1 was affected in both amplitude and oscillatory pattern. We next treated mice with a β‐adrenergic receptor (β‐AR) blocker. Strikingly, the β‐AR blockade during the day suppressed the nocturnal increase in Per1 mRNA, without altering Clock or Bmal1. In contrast, activating β‐AR with isoproterenol (ISO) promoted an increase in Per1 expression, demonstrating its responsiveness to adrenergic input. Inhibitors of ERK1/2 and CREB attenuated ISO‐induced Per1 expression. Upstream of ERK1/2, PI3Kγ mediated ISO induction of Per1 transcription, while activation of β2‐AR, but not β1‐AR induced increases in ERK1/2 phosphorylation and Per1 expression. Consistent with the β2‐induction of Per1 mRNA, ISO failed to activate ERK1/2 and elevate Per1 in the heart of β2‐AR−/− mice, whereas a β2‐AR antagonist attenuated the nocturnal rise in Per1 expression. Our study established a link between NE/β2‐AR signaling and Per1 oscillation via the PI3Ky‐ERK1/2‐CREB pathway, providing a new framework for understanding the physiological mechanism involved in resetting cardiac clock genes.
•Esketamine 0.25 mg/kg was noninferior to ketamine 0.5 mg/kg in promoting remission of major depression symptoms 24 h after a single intravenous administration in subjects with treatment-resistant ...depression.•Esketamine and ketamine demonstrated a similar safety pattern and were well tolerated by most participants.•This is the first head-to-head randomized clinical trial comparing racemic ketamine and esketamine in patients with treatment-resistant depression.
Ketamine and its enantiomers have recently been highlighted as one of the most effective therapeutic options in refractory depression. However, racemic ketamine and esketamine have not been directly compared. The aim of this study is to assess the efficacy and safety of esketamine compared to ketamine in patients with treatment-resistant depression (TRD).
This is a randomized, double-blind, active-controlled, bicentre, non-inferiority clinical trial, with two parallel groups. Participants were randomly assigned to a 40-min single intravenous infusion of ketamine 0.5 mg/kg or esketamine 0.25 mg/kg. The primary outcome was the difference in remission rates for depression 24 h following intervention using the Montgomery-Åsberg Depression Rating Scale (MADRS), with a non-inferiority margin of 20%.
63 subjects were included and randomly assigned (29 to receive ketamine and 34 to receive esketamine). At 24 h, 24.1% of participants in the ketamine group and 29.4% of participants in the esketamine group showed remission, with a difference of 5.3% (95% CILB -13.6%), confirming non-inferiority. MADRS scores improved from 33 (SD 9.3) to 16.2 (SD 10.7) in the ketamine group and from 33 (SD 5.3) to 17.5 (SD 12.2) in the esketamine one, with a difference of -5.27% (95% CILB, -13.6). Both groups presented similar mild side effects.
Esketamine was non-inferior to ketamine for TRD 24 h following infusion. Both treatments were effective, safe, and well tolerated.
Registered in Japan Primary Registries Network: UMIN000032355.
Objectives
The aim of this study was to evaluate the expression of Akt, PTEN, Mdm2 and p53 proteins in three different head and neck squamous cell carcinoma (HNSCC) cell lines (HN6, HN19 and HN30), ...all of them treated with epidermal growth factor (EGF) and 17‐allylamino‐17‐demethoxygeldanamycin (17‐AAG), an inhibitor of Hsp90 protein.
Material and Methods
Immunofluorescence and western blot were performed in order to analyze the location and quantification, respectively, of proteins under the action 17‐AAG and EGF.
Results
Treatment with EGF resulted in increased levels of Akt, PTEN and p53 in all cell lineages. The expression of Mdm2 was constant in HN30 and HN6 lineages, while in HN19 showed slightly decreased expression. Under the action 17‐AAG, in HN6 and HN19, the expression of PTEN and p53 proteins was suppressed, while Akt and Mdm2 expression was reduced. Finally, in the HN30 cell lineage were absolute absence of expression of Akt, Mdm2 and p53 and decreased expression of PTEN.
Conclusion
These data allow us to speculate on the particular utility of 17‐AAG for HNSCC treatment through the inhibition of Akt protein expression, especially in the cases that retain the expression of PTEN protein.
In
cultures, three species of
are known to cause distinct diseases.
subsp.
patothype A,
subsp.
pathotypes B and C, and
subsp.
, are the causative agents of cancrosis A, B, C, and citrus bacterial ...spots, respectively. Although these species exhibit different levels of virulence and aggressiveness, only limited alternatives are currently available for proper and early detection of these diseases in the fields. The present study aimed to develop a new molecular diagnostic method based on genomic sequences derived from the four species of
.
Using comparative genomics approaches, primers were synthesized for the identification of the four causative agents of citrus diseases. These primers were validated for their specificity to their target DNA by both conventional and multiplex PCR. Upon evaluation, their sensitivity was found to be 0.02 ng/µl
and 1.5 × 10
CFU ml
in infected leaves. Additionally, none of the primers were able to generate amplicons in 19 other genomes of
not associated with
and one species of
, the causal agent of citrus variegated chlorosis (CVC). This denotes strong specificity of the primers for the different species of
investigated in this study.
We demonstrated that these markers can be used as potential candidates for performing
molecular diagnosis exclusively for citrus-associated
. The bioinformatics pipeline developed in this study to design specific genomic regions is capable of generating specific primers. It is freely available and can be utilized for any other model organism.
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