Identification of the atypical antipsychotic Asenapine as a direct survivin inhibitor with anticancer properties and sensitizing effects to conventional therapies.

Therapy resistance in human cancers is a major limitation in Clinical Oncology. In this regard, overexpression of anti-apoptotic proteins, such as survivin, has been described in several tumors, contributing to this clinical issue. Survivin has a dual role in key cellular functions, inducing cell cycle progression and inhibiting apoptosis; thus, survivin is an attractive target for cancer therapy.

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

Background: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear.

Electroencephalographic activity during direct breastfeeding and breast milk expression in primiparous mothers.

Breastfeeding is recognized worldwide as the best option for infant feeding. Expressing breast milk is an alternative for mothers to provide their infants all the benefits of maternal milk. During breast milk expression, mothers receive a distinct kind of sensory stimulation, because there is no direct bodily or affective interaction with their infants, many women report feeling isolated, generating a love-hate relation with pumping, and even low levels of satisfaction while expressing breast milk.

The distribution and diversity of eukaryotic phytoplankton in the Icelandic marine environment.

Phytoplankton play a crucial role in the marine food web and are sensitive indicators of environmental change. Iceland is at the center of a contrasting hydrography, with cold Arctic water coming in from the north and warmer Atlantic water from the south, making this geographical location very sensitive to climate change. We used DNA metabarcoding to determine the biogeography of phytoplankton in this area of accelerating change.

From -Values to Posterior Probabilities of Null Hypotheses.

Minimum Bayes factors are commonly used to transform two-sided -values to lower bounds on the posterior probability of the null hypothesis, in particular the bound -e·p·log(p). This bound is easy to compute and explain; however, it does not behave as a Bayes factor. For example, it does not change with the sample size.

Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by high propensity to life-threatening arrhythmias and progressive loss of heart muscle. More than 40% of reported genetic variants linked to ARVC reside in the gene, which encodes the PKP2 protein (plakophilin-2).

Methods: We describe a comprehensive characterization of the ARVC molecular landscape as determined by high-resolution mass spectrometry, RNA sequencing, and transmission electron microscopy of right ventricular biopsy samples obtained from patients with ARVC with mutations and left ventricular ejection fraction >45%.

Activation of Peripheral Cannabinoid Receptors Synergizes the Effect of Systemic Ibuprofen in a Pain Model in Rat.

Pharmacological synergism is a current strategy for the treatment of pain. However, few studies have been explored to provide evidence of the possible synergism between a non-steroidal anti-inflammatory drug (NSAID) and a cannabinoid agonist, in order to establish which combinations might be effective to manage pain. The aim of this study was to explore the synergism between ibuprofen (IBU) and the synthetic cannabinoid WIN 55,212-2 (WIN) to improve pain relief by analyzing the degree of participation of the CB and CB cannabinoid receptors in the possible antinociceptive synergism using an experimental model of pain in Wistar rats.

Preserved cardiac performance and adrenergic response in a rabbit model with decreased ryanodine receptor 2 expression.

Ryanodine receptor 2 (RyR2) is an ion channel in the heart responsible for releasing into the cytosol most of the Ca required for contraction. Proper regulation of RyR2 is critical, as highlighted by the association between channel dysfunction and cardiac arrhythmia. Lower RyR2 expression is also observed in some forms of heart disease; however, there is limited information on the impact of this change on excitation-contraction (e-c) coupling, Ca-dependent arrhythmias, and cardiac performance.

Alveolar Proteinosis Secondary to , in a Patient with Transient CD4 Lymphocytopenia Due to Infection: First Case in the Literature.

Transient CD4 lymphocytopenia is defined as the transitory presence of CD4+ T lymphocyte fewer than 300 cells/mm or less than 20% of T cells without HIV infection. It can occur due to multiple causes; however, it is rare for it to occur due to opportunistic infections. Few cases have been described in the literature where antimicrobial treatment normalizes the CD4 count, being more frequent in infections.

Role of plakophilin-2 expression on exercise-related progression of arrhythmogenic right ventricular cardiomyopathy: a translational study.

Aims: Exercise increases arrhythmia risk and cardiomyopathy progression in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, but the mechanisms remain unknown. We investigated transcriptomic changes caused by endurance training in mice deficient in plakophilin-2 (PKP2cKO), a desmosomal protein important for intercalated disc formation, commonly mutated in ARVC and controls.

Methods And Results: Exercise alone caused transcriptional downregulation of genes coding intercalated disk proteins.

Coordination of endothelial cell positioning and fate specification by the epicardium.

The organization of an integrated coronary vasculature requires the specification of immature endothelial cells (ECs) into arterial and venous fates based on their localization within the heart. It remains unclear how spatial information controls EC identity and behavior. Here we use single-cell RNA sequencing at key developmental timepoints to interrogate cellular contributions to coronary vessel patterning and maturation.

Targeting the Microtubule EB1-CLASP2 Complex Modulates Na1.5 at Intercalated Discs.

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Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug.

Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment.

Multiparity decreases the effect of distractor stimuli on a working memory task: An EEG study.

Parity modulates the way in which women respond to infant's affective cues. It is known that the cognitive processing of mothers is affected by a baby crying; however, little information is available regarding the effect of reproductive and caregiving experience on efficiency in managing babies' emotional stimuli while other tasks are being attended. This study characterized the affective score, cognitive performance, and electroencephalographic correlation (rEEG) between prefrontal and parietal cortices in first- (FM) and second-time mothers (SM) while solving a working memory task (vsWM) and simultaneously listening to either an emotional or neutral distractor stimulus.

Cx43 hemichannel microdomain signaling at the intercalated disc enhances cardiac excitability.

Cx43, a major cardiac connexin, forms precursor hemichannels that accrue at the intercalated disc to assemble as gap junctions. While gap junctions are crucial for electrical conduction in the heart, little is known about the potential roles of hemichannels. Recent evidence suggests that inhibiting Cx43 hemichannel opening with Gap19 has antiarrhythmic effects.

Increased kynurenine concentration attenuates serotonergic neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats through activation of aryl hydrocarbon receptor.

3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that has been shown to produce serotonergic damage in the brains of primates, including humans, and of rats. Tryptophan, the precursor of serotonin, is primarily degraded through the kynurenine (KYN) pathway, producing among others KYN, the main metabolite of this route. KYN has been reported as an endogenous agonist of the aryl hydrocarbon receptor (AhR), a transcription factor involved in several neurological functions.

Transcriptomic Coupling of PKP2 With Inflammatory and Immune Pathways Endogenous to Adult Cardiac Myocytes.

Plakophilin-2 (PKP2) is classically defined as a component of the desmosome. Besides its role in cell-cell adhesion, PKP2 can modulate transcription through intracellular signals initiated at the site of cell-cell contact. Mutations in associate with arrhythmogenic right ventricular cardiomyopathy (ARVC).

Addiction and the kynurenine pathway: A new dancing couple?

Drug use poses a serious threat to health systems throughout the world and the number of consumers rises relentlessly every year. The kynurenine pathway, main pathway of tryptophan degradation, has drawn interest in this field due to its relationship with addictive behaviour. Recently it has been confirmed that modulation of kynurenine metabolism at certain stages of the pathway can reduce, prevent or abolish drug seeking-like behaviours in studies with several different drugs.

Structural and Functional Characterization of a Na1.5-Mitochondrial Couplon.

Rationale: The cardiac sodium channel Na1.5 has a fundamental role in excitability and conduction. Previous studies have shown that sodium channels cluster together in specific cellular subdomains.

The p.P888L SAP97 polymorphism increases the transient outward current (I) and abbreviates the action potential duration and the QT interval.

Synapse-Associated Protein 97 (SAP97) is an anchoring protein that in cardiomyocytes targets to the membrane and regulates Na and K channels. Here we compared the electrophysiological effects of native (WT) and p.P888L SAP97, a common polymorphism.

Ankyrin-G mediates targeting of both Na and K channels to the rat cardiac intercalated disc.

We investigated targeting mechanisms of Na and K channels to the intercalated disk (ICD) of cardiomyocytes. Patch clamp and surface biotinylation data show reciprocal downregulation of each other's surface density. Mutagenesis of the Kir6.

The effect of aromatherapy with lavender (Lavandula angustifolia) on serum melatonin levels.

Objective: Physiologically, blood melatonin levels decrease as a person ages and the older adult commonly presents with insomnia and other types of sleep disorders. Alternative therapies can be used to attenuate sleep disturbances. The aim of the present study was to analyze the effect of aromatherapy with lavender on serum melatonin levels in the noninstitutionalized older adult (OA).

Targeting Autophagy for Cancer Treatment and Tumor Chemosensitization.

Autophagy is a tightly regulated catabolic process that facilitates nutrient recycling from damaged organelles and other cellular components through lysosomal degradation. Deregulation of this process has been associated with the development of several pathophysiological processes, such as cancer and neurodegenerative diseases. In cancer, autophagy has opposing roles, being either cytoprotective or cytotoxic.