Stabilization of GTSE1 by cyclin D1-CDK4/6 promotes cell proliferation: relevance in cancer prognosis.

Cyclin D1 is the activating subunit of the cell cycle kinases CDK4 and CDK6, and its dysregulation is a well-known oncogenic driver in many human cancers. The biological function of cyclin D1 has been primarily studied by focusing on the phosphorylation of the retinoblastoma (RB) gene product. Here, using an integrative approach combining bioinformatic analyses and biochemical experiments, we show that GTSE1 (G2 and S phases expressed protein 1), a protein positively regulating cell cycle progression, is a previously unknown substrate of cyclin D1-CDK4/6.

A Methodology for Multivariate Investigation on the Effect of Acrylate Molecular Structure on the Mechanical Properties and Delivery Efficiency of Microcapsules via In Situ Polymerization.

In the field of encapsulation, microcapsules containing perfume have emerged as effective vehicles for delivering active ingredients across various applications. The present study employed a multivariate analysis framework to examine polyacrylate microcapsules for household products synthesized using different acrylate monomers. The advanced multivariate approach allowed us to quantify critical properties such as the (), mechanical attributes, (), and .

Six-item cognitive impairment test (6-CIT)'s accuracy as a cognitive screening tool: best cut-off levels in emergency department setting.

Background: Nowadays, elderly patients represent a significant number of accesses to the Emergency Department (ED). Working rhythms do not allow to perform complete cognitive analysis, which would, however, be useful for the health care. This study aims to define the optimal cut-off values of the six-item Cognitive Impairment Test (6-CIT) as a cognitive screening tool in ED.

Effects of memantine on mania-like phenotypes exhibited by Drosophila Shaker mutants.

Introduction: Increased glutamate levels and electrolytic fluctuations have been observed in acutely manic patients. Despite some efficacy of the non-competitive NMDA receptor antagonist memantine (Mem), such as antidepressant-like and mood-stabilizer drugs in clinical studies, its specific mechanisms of action are still uncertain. The present study aims to better characterize the Drosophila melanogaster fly Shaker mutants (SH), as a translational model of manic episodes within bipolar disorder in humans, and to investigate the potential anti-manic properties of Mem.

Upregulation of p75NTR by Histone Deacetylase Inhibitors Sensitizes Human Neuroblastoma Cells to Targeted Immunotoxin-Induced Apoptosis.

Histone deacetylase (HDAC) inhibitors are novel chemotherapy agents with potential utility in the treatment of neuroblastoma, the most frequent solid tumor of childhood. Previous studies have shown that the exposure of human neuroblastoma cells to some HDAC inhibitors enhanced the expression of the common neurotrophin receptor p75NTR. In the present study we investigated whether the upregulation of p75NTR could be exploited to render neuroblastoma cells susceptible to the cytotoxic action of an anti-p75NTR antibody conjugated to the toxin saporin-S6 (p75IgG-Sap).

Understanding the self-assembly of the polymeric drug solubilizer Soluplus®.

Hypothesis: Soluplus® is one of the most widely used amphiphilic copolymers in drug delivery and has been reported to strongly enhance the adsorption of model drugs. However, there is still a limited understanding of its micellar behavior as it responds to the different routes of administration, which involve important changes in concentration.

Experiments: The microstructure of Soluplus aqueous solutions has been investigated at a wide range of polymer concentrations (2 × 10 - 0.

Phylobioactive hotspots in plant resources used to treat Chagas disease.

Globally, more than six million people are infected with , the causative protozoan parasite of the vector-borne Chagas disease (CD). We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups where CD is hyperendemic. A total of 775 extracts of botanical drugs used in Bolivia in the context of CD and botanical drugs from unrelated indications from the Mediterranean a compiled by Dioscorides two thousand years ago were profiled in a multidimensional assay uncovering different antichagasic natural product classes.

Suppressing effect of the novel positive allosteric modulator of the GABA receptor, COR659, on locomotor hyperactivity induced by different drugs of abuse.

COR659 is a recently synthesized positive allosteric modulator (PAM) of the GABA receptor. Similarly to all GABA PAMs tested to date, COR659 has been reported to suppress different alcohol-related behaviors in rodents. The present study was designed to assess whether the anti-addictive properties of COR659 extend to drugs of abuse other than alcohol.

Specific Anion Effects on Lipase Adsorption and Enzymatic Synthesis of Biodiesel in Nonaqueous Media.

lipase (Pfl) was adsorbed on macroporous polypropylene to obtain a heterogeneous biocatalyst. The effect of NaCl concentration and of different 100 mm sodium salts on the Pfl loading and catalytic performance toward biodiesel synthesis via the solvent-free methanolysis of triglycerides was studied. Although lipase adsorption onto polypropylene is governed by hydrophobic interactions, both salt concentration and anion type affect lipase loading.

Offshore multi-purpose platforms for a Blue Growth: A technological, environmental and socio-economic review.

"Blue Growth" and "Blue Economy" is defined by the World Bank as: "the sustainable use of ocean resources for economic growth, improved livelihoods and jobs, while preserving the health of ocean ecosystem". Multi-purpose platforms (MPPs) can be defined as offshore platforms serving the needs of multiple offshore industries (energy and aquaculture), aim at exploiting the synergies and managing the tensions arising when closely co-locating systems from these industries. Despite a number of previous projects aimed at assessing, from a multidisciplinary point of view, the feasibility of multipurpose platforms, it is here shown that the state-of-the-art has focused mainly on single-purpose devices, and adopting a single discipline (either economic, or social, or technological, or environmental) approach.

Essential fatty acids deficient diet modulates N-Acylethanolamide profile in rat's tissues.

No data are available on whether a diet deficient of the essential fatty acids is able to modulate tissue levels of endocannabinoids and congeners. Male rats fed for 12 weeks a diet deficient of essential fatty acids, palmitic and oleic acids (EFAD), replaced with saturated fatty acids (SAFA), showed lowered n-3 and n-6 PUFAs levels in plasma, liver and adipose tissue, with concomitant steep increase of oleic and mead acids, while in hypothalamus no changes in PUFA concentration were detected and only palmitoleic acid was found increased. We found a reduction of anandamide and palmitoylethanolamide in liver and brain, while oleoylethanolamide increased significantly in liver and adipose tissue, associated to a 50 % body weight decrease.

Improvements of Motor Performances in the Loss-of-Function Model of Parkinson's Disease: Effects of Dialyzed Leucocyte Extracts from Human Serum.

Within neurodegenerative syndromes, Parkinson's disease (PD) is typically associated with its locomotor defects, sleep disturbances and related dopaminergic (DA) neuron loss. The fruit fly, (), with leucine-rich repeat kinase 2 mutants () loss-of-function in the WD40 domain, provides mechanistic insights into corresponding human behaviour, possibly disclosing some physiopathologic features of PD in both genetic and sporadic forms. Moreover, several data support the boosting impact of innate and adaptive immunity pathways for driving the progression of PD.

A case-control study of Drug-Induced Sleep Endoscopy (DISE) in pediatric population: A proposal for indications.

Objective: To evaluate whether and when Drug-Induced Sleep Endoscopy (DISE) changes diagnosis and treatment plan in pediatric Obstructive Sleep Apnoea Syndrome (OSAS) with the aim to identify specific subgroups of patients for whom DISE should be especially considered.

Methods: A case-control study of DISE in 150 children with OSAS. Pre-operative OSA were assessed through detailed history, Chervin questionnaire, physical examination and overnight polysomnography.

Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion.

Background: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) has been shown to stimulate early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The aim of the present study is to probe the possibility to prevent the molecular changes induced by the BCCAO/R with dietary natural compounds known to possess anti-inflammatory activity, such as the phytocannabinoid beta-caryophyllene (BCP).

Methods: Two groups of adult Wistar rats were used, sham-operated and submitted to BCCAO/R.

Preventive Effects of Resveratrol on Endocannabinoid System and Synaptic Protein Modifications in Rat Cerebral Cortex Challenged by Bilateral Common Carotid Artery Occlusion and Reperfusion.

This study aims to evaluate the putative roles of a single acute dose of resveratrol (RVT) in preventing cerebral oxidative stress induced by bilateral common carotid artery occlusion, followed by reperfusion (BCCAO/R) and to investigate RVT's ability to preserve the neuronal structural integrity. Frontal and temporal-occipital cortices were examined in two groups of adult Wistar rats, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half the rats were gavage-fed with a single dose of RVT (40 mg/per rat in 300 µL of sunflower oil as the vehicle), while the second half received the vehicle alone.

Involvement of the endocannabinoid system in the physiological response to transient common carotid artery occlusion and reperfusion.

Background: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma.

Differential effects of the MEK inhibitor SL327 on the acquisition and expression of ethanol-elicited conditioned place preference and aversion in mice.

The involvement of mitogen-activating extracellular kinase (MEK) in place conditioning may vary depending on the motivational sign (positive or negative) and nature (pharmacological or nociceptive) of the unconditioned stimulus (US) and on the phase (acquisition or expression) of the learning process. This study investigated the role of MEK on the acquisition and expression of ethanol-elicited (given 2 g/kg) backward (preference, CPP) and forward (aversion, CPA) place conditioning. The MEK inhibitor SL327 (50 mg/kg for CPP, and 50 and 100 mg/kg for CPA) was administered to CD-1 mice 60 minutes before an ethanol dose (acquisition) or 60 minutes before the post-conditioning tests (expression).

Multidrug resistance P-glycoprotein dampens SR-BI cholesteryl ester uptake from high density lipoproteins in human leukemia cells.

Tumor cells are characterised by a high content of cholesterol esters (CEs), while tumor-bearing patients show low levels of high-density lipoproteins (HDLs). The origin and significance of high CE levels in cancer cell biology has not been completely clarified. Recent evidence that lymphoblastic cells selectively acquire exogenous CE from HDL via the scavenger receptor SR-BI has drawn attention to the additional membrane proteins involved in this pathway.

Is 1p36 deletion associated with anterior body wall defects?

Epispadias and exstrophy of the cloaca, also known as OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects), respectively constitute the most benign and severe ends of the bladder exstrophy-epispadias complex (BEEC) spectrum. In 2009, El-Hattab et al. reported the first patient with OEIS complex associated with a chromosome 1p36 deletion.

High-density lipoprotein contribute to G0-G1/S transition in Swiss NIH/3T3 fibroblasts.

High density lipoproteins (HDLs) play a crucial role in removing excess cholesterol from peripheral tissues. Although their concentration is lower during conditions of high cell growth rate (cancer and infections), their involvement during cell proliferation is not known. To this aim, we investigated the replicative cycles in synchronised Swiss 3T3 fibroblasts in different experimental conditions: i) contact-inhibited fibroblasts re-entering cell cycle after dilution; ii) scratch-wound assay; iii) serum-deprived cells induced to re-enter G1 by FCS, HDL or PDGF.

Withania somnifera Dunal (Indian ginseng) impairs acquisition and expression of ethanol-elicited conditioned place preference and conditioned place aversion.

Withania somnifera Dunal (Indian Ginseng) has recently been shown to impair ethanol self-administration. In order to gain further insights on the ability of the Withania somnifera standardised root extract (WSE) to affect the motivational properties of ethanol, this study investigated whether WSE may also affect ethanol (2 g/kg)-elicited conditioned place preference (CPP) and aversion (CPA). To this end male CD-1 mice were conditioned under two distinct schedules: in backward conditioning experiments ethanol was administered before mice were placed in the conditioning apparatus (CPP) while, in forward conditioning experiments, ethanol was administered immediately after removing mice from the apparatus (CPA).

Dietary triacylglycerols with palmitic acid in the sn-2 position modulate levels of N-acylethanolamides in rat tissues.

Background: Several evidences suggest that the position of palmitic acid (PA) in dietary triacylglycerol (TAG) influences different biological functions. We aimed at evaluating whether dietary fat with highly enriched (87%) PA in sn-2 position (Hsn-2 PA), by increasing PA incorporation into tissue phospholipids (PL), modifies fatty acid profile and biosynthesis of fatty acid-derived bioactive lipids, such as endocannabinoids and their congeners.

Study Design: Rats were fed for 5 weeks diets containing Hsn-2 PA or fat with PA randomly distributed in TAG with 18.

A comparison between the dynamics of horizontal and vertical axis offshore floating wind turbines.

The need to further exploit offshore wind resources in deeper waters has led to a re-emerging interest in vertical axis wind turbines (VAWTs) for floating foundation applications. However, there has been little effort to systematically compare VAWTs to the more conventional horizontal axis wind turbine (HAWT). This article initiates this comparison based on prime principles, focusing on the turbine aerodynamic forces and their impact on the floating wind turbine static and dynamic responses.

Effect of memantine on L-DOPA-induced dyskinesia in the 6-OHDA-lesioned rat model of Parkinson's disease.

An increasing body of experimental evidence demonstrates that the glutamatergic system is involved in the genesis of l-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID). Indeed, the N-methyl-d-aspartate (NMDA) receptor antagonist amantadine is the only anti-dyskinetic compound used in patients, albeit with limited efficacy and side effects. In this study, we investigated the anti-dyskinetic properties of memantine, a non-competitive NMDA receptor antagonist in clinical use for the treatment of dementia, in the 6-hydroxy-dopamine (6-OHDA)-lesion rat model of Parkinson's disease.