Several studies have described a potential anti-tumour effect of cannabinoids (CNB). CNB receptor 2 (CB2) is mostly present in hematopoietic stem cells (HSC). The present study evaluates the ...anti-leukaemic effect of CNB.
Cell lines and primary cells from acute myeloid leukaemia (AML) patients were used and the effect of the CNB derivative WIN-55 was evaluated in vitro, ex vivo and in vivo.
We demonstrate a potent antileukemic effect of WIN-55 which is abolished with CB antagonists. WIN-treated mice, xenografted with AML cells, had better survival as compared to vehicle or cytarabine. DNA damage-related genes were affected upon exposure to WIN. Co-incubation with the PARP inhibitor Olaparib prevented WIN-induced cell death, suggesting PARP-mediated apoptosis which was further confirmed with the translocation of AIF to the nucleus observed in WIN-treated cells. Nicotinamide prevented WIN-related apoptosis, indicating NAD+ depletion. Finally, WIN altered glycolytic enzymes levels as well as the activity of G6PDH. These effects are reversed through PARP1 inhibition.
WIN-55 exerts an antileukemic effect through Parthanatos, leading to translocation of AIF to the nucleus and depletion of NAD+, which are reversed through PARP1 inhibition. It also induces metabolic disruptions. These effects are not observed in normal HSC.
The concept of aberrant salience is related to the onset of psychosis. Its study is important for early identification and possible intervention in processes activating later positive symptoms.
This ...study validated the Spanish Aberrant Salience Inventory (ASI) for adult and clinical populations.
The sample consisted of 6178 participants, of whom 4523 were adolescents, 1292 were general population adults and 363 were patients with a psychopathology.
The evidence provided validates the instrument's structure. Invariance of measurement suggests that both men and women, patients and nonclinical population (adults and adolescents) interpreted the items on the ASI similarly. The distribution of scores by age also suggests stabilization of the trend at about 19 years of age, showing a developmental change in motivational response. The hypothesis that patients, and in particular, those diagnosed with schizophrenia and other psychotic disorders and bipolar disorders would have the highest average scores in aberrant salience was met.
This is a valuable instrument for evaluating a complex process related to abnormal motivation in the development of schizophrenia.
•The importance of an instrument for evaluating aberrant salience (abnormal motivation)•Invariance of aberrant salience across sexes, patients and nonclinical population•Stabilization about 19 years of age: a developmental change in motivational response•Schizophrenia and bipolar disorders had the highest average in aberrant salience
The excitation–contraction coupling (ECC) in skeletal muscle refers to the Ca
2+
-mediated link between the membrane excitation and the mechanical contraction. The initiation and propagation of an ...action potential through the membranous system of the sarcolemma and the tubular network lead to the activation of the Ca
2+
-release units (CRU): tightly coupled dihydropyridine and ryanodine (RyR) receptors. The RyR gating allows a rapid, massive, and highly regulated release of Ca
2+
from the sarcoplasmic reticulum (SR). The release from triadic places generates a sarcomeric gradient of Ca
2+
concentrations (Ca
2+
) depending on the distance of a subcellular region from the CRU. Upon release, the diffusing Ca
2+
has multiple fates: binds to troponin C thus activating the contractile machinery, binds to classical sarcoplasmic Ca
2+
buffers such as parvalbumin, adenosine triphosphate and, experimentally, fluorescent dyes, enters the mitochondria and the SR, or is recycled through the Na
+
/Ca
2+
exchanger and store-operated Ca
2+
entry (SOCE) mechanisms. To commemorate the 7
th
decade after being coined, we comprehensively and critically reviewed “old”, historical landmarks and well-established concepts, and blended them with recent advances to have a complete, quantitative-focused landscape of the ECC. We discuss the: 1) elucidation of the CRU structures at near-atomic resolution and its implications for functional coupling; 2) reliable quantification of peak sarcoplasmic Ca
2+
using fast, low affinity Ca
2+
dyes and the relative contributions of the Ca
2+
-binding mechanisms to the whole concert of Ca
2+
fluxes inside the fibre; 3) articulation of this novel quantitative information with the unveiled structural details of the molecular machinery involved in mitochondrial Ca
2+
handing to understand how and how much Ca
2+
enters the mitochondria; 4) presence of the SOCE machinery and its different modes of activation, which awaits understanding of its magnitude and relevance
in situ
; 5) pharmacology of the ECC, and 6) emerging topics such as the use and potential applications of super-resolution and induced pluripotent stem cells (iPSC) in ECC. Blending the old with the new works better!
This multicenter phase I trial was designed to evaluate the safety and efficacy of bortezomib (Bz) as part of both the conditioning regimen and the graft-versus-host disease (GvHD) prophylaxis. ...Patients received fludarabine, melphalan and Bz (days -9 and -2). GVHD prophylaxis consisted of Bz (days +1, +4, and +7), sirolimus (Siro) from day -5 and tacrolimus (Tk) from -3 (except the first five patients that did not receive Tk). Twenty-five patients with poor prognostic multiple myeloma were included. Eleven out of the 19 patients had high-risk features. Out of the 21 patients evaluable at day +100, 14 were in CR (67%) and 7 (33%) in PR. Cumulative incidence (CI) of nonrelapse mortality at 1 year was 24%. CI of grades 2-4 and 3-4 acute GvHD was 35% and 10%, respectively; CI of chronic GvHD was 35% and 55% at 1 and 2 years, respectively. Overall and event free survival at 2 years were 64% and 31%, respectively. Bz as part of the conditioning regimen and in the combination with Siro/tacrolimus for GvHD prophylaxis is safe and effective allowing an optimal disease control early after transplant and reducing the risk of GvHD.
Acceleration of wound healing can be achieved with the use of wound dressings. Through the electrospinning technique, a polymeric scaffold composed of two layers was processed: a gelatin and ...polyvinylpyrrolidone layer with gentamicin, and a second layer of cellulose acetate. The conditions for the electrospinning process were standardized for voltage parameters, feed flow and the distance from the injector to the collector. Once the values of the main variables for the electrospinning were optimized, a three-hour processing time was established to allow the separation of the material from the collector. The obtained material was characterized by observations on scanning electron microscopy, Fourier transform infrared spectroscopy and thermal analysis; contact angle measurement was performed to evaluate wettability properties, and antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus were evaluated using the Kirby–Bauer test. The obtained fibers that form the bi-layer scaffold present diameters from 100 to 300 nm. The scaffold presents chemical composition, thermal stability, wettability characteristics and antibacterial activity that fulfill the proposal from this study, based on obtaining a scaffold that could be used as a drug delivery vehicle and a wound dressing material.
We discuss a sharpened Hausdorff–Young inequality and estimate the maximal coefficients of orthogonal expansions in terms of Freud polynomials when
1
<
p
<
2
and
2
<
p
<
∞
. We also consider
n
...-dimensional expansions by orthogonal functions associated to Freud-type weights when
1
<
p
<
2
.
•The granular nanotubes calcination of cobalt ferrite produces octahedrons.•Particles grow as octahedrons due to a minimization of the surface free-energy.•The heat treatment increases the sizes of ...the crystallites and particles.•The curves ZFC and FC are characterized by a peak and irreversibility temperatures.•Irreversibility temperature behavior is similar to superparamagnetic systems.•The magnetic domain structure is highly dependent on the applied magnetic field.
We present an in-depth magnetic study of polycrystalline, microstain-free, magnetic, and thermally stable cobalt ferrite (CoFe2O4) octahedrons with an edge dimension of 214 nm. Nanoparticles were synthesized from granular CoFe2O4 nanotubes growing on bacterial nanocellulose and annealed at T = 1273 K. SEM, XRD, and VSM were used to investigate the morphology, structure and magnetic properties of the octahedral particles. The results indicate that heat treatment increases the sizes of the crystallites (2 times) and of the particles (4 times), compared with the starting material. The particles show a change of the magnetization saturation and magnetic anisotropy around 150 K compared with canonical ferrimagnetic materials, associated with a First Order Magnetization Process. The magnetization process as a function of temperature, cooling without (ZFC) and with (FC) different applied magnetic fields are explained by multi-domain theory. ZFC-FC curves show an irreversible branching temperature, which is highly sensitive to the applied magnetic field. In contrast, the temperature for the maximal magnetization value in the ZFC curves, change slightly with the external applied magnetic field, H.
Abstract
OBJECTIVES
The mechanistic understanding of vascular functional impairment during preservation time helps determine the optimal time frame in which explanted arteries can be used. The method ...of choice is to measure vascular reactivity and receptor expression. Our goal was to study the influence of preservation for 24 and 48 h on vascular reactivity and receptor expression in rabbit aorta.
METHODS
Aortic rings preserved in Krebs–Henseleit solution were evaluated fresh (t0), 24 h (t24) and 48 h (t48) after harvest for (i) vascular reactivity as sensitivity (pD2) and maximum effect in response to potassium chloride, U46619 (thromboxane-A2 agonist), phenylephrine, carbachol and isoproterenol, in an organ bath; and for (ii) expression of α1, β2 and thromboxane-prostanoid receptors, by immunofluorescence.
RESULTS
Compared to the control, after 24 h of preservation, potassium chloride-induced pD2 increased a significant 3.6%, whereas U46619-induced vasoconstriction decreased 9%. None of the agonists affected vasodilation. Intimal and medial α1 receptor expression increased 2.5-fold. After 48 h of preservation, α1 expression and vasoconstrictor responses remained similar to those after 24 h of preservation, but in vasodilation the carbachol-induced maximum effect decreased 30% whereas isoproterenol-induced pD2 increased 4% and the maximum effect increased 10%. TP and β2 expression in the intima and media increased 1.8- and 2.5-fold, respectively.
CONCLUSIONS
Up to 48 h of preservation, the adrenergic pathway and its receptors support vasoconstriction and vasodilation, despite a significant deterioration in the prostanoid pathway.
Myonectin has shown beneficial effects on lipid regulation in murine models; therefore, it may have implications in the pathophysiology of metabolic syndrome (MS). We evaluated the relationship ...between serum myonectin and serum lipids, global and regional fat mass, intramuscular lipid content, and insulin resistance (IR) in adults with metabolic risk factors. This was a cross-sectional study in sedentary adults who were diagnosed with MS or without MS (NMS). Serum myonectin was quantified by enzyme-linked immunosorbent assay, lipid profile by conventional techniques, and free fatty acids (FFA) by gas chromatography. Body composition was assessed by dual-energy X-ray absorptiometry and intramuscular lipid content through proton nuclear magnetic resonance spectroscopy in the right vastus lateralis muscle. IR was estimated with the homeostatic model assessment (HOMA-IR). The MS (
= 61) and NMS (
= 29) groups were comparable in age (median (interquartile range): 51.0 (46.0-56.0) vs. 53.0 (45.5-57.5) years,
> 0.05) and sex (70.5% men vs. 72.4% women). MS subjects had lower serum levels of myonectin than NMS subjects (1.08 (0.87-1.35) vs. 1.09 (0.93-4.05) ng·mL
,
< 0.05). Multiple linear regression models adjusted for age, sex, fat mass index and lean mass index showed that serum myonectin was negatively correlated with the android/gynoid fat mass ratio (R
= 0.48,
< 0.01), but not with the lipid profile, FFA, intramuscular lipid content or HOMA-IR. In conclusion, serum myonectin is lower in subjects with MS. Myonectin negatively correlates with a component relevant to the pathophysiology of MS, such as the android/gynoid fat mass ratio, but not with other components such as FFA, intramuscular fat or IR.
PDF
