Suppression of MT5-MMP Reveals Early Modulation of Alzheimer's Pathogenic Events in Primary Neuronal Cultures of 5xFAD Mice.

We previously reported that membrane-type 5-matrix metalloproteinase (MT5-MMP) deficiency not only reduces pathological hallmarks of Alzheimer's disease (AD) in 5xFAD (Tg) mice in vivo but also impairs interleukin-1 beta (IL-1β)-mediated neuroinflammation and Aβ production in primary Tg immature neural cell cultures after 11 days in vitro. We now investigate the effect of MT5-MMP on incipient pathogenic pathways that are activated in cortical primary cultures at 21-24 days in vitro (DIV), during which time neurons are organized into a functional mature network. Using wild-type (WT), MT5-MMP (MT5), 5xFAD (Tg), and 5xFADxMT5-MMP (TgMT5) mice, we generated primary neuronal cultures that were exposed to IL-1β and/or different proteolytic system inhibitors.

Missense mutations of the ephrin receptor EPHA1 associated with Alzheimer's disease disrupt receptor signaling functions.

Missense mutations in the EPHA1 receptor tyrosine kinase have been identified in Alzheimer's patients. To gain insight into their potential role in disease pathogenesis, we investigated the effects of four of these mutations. We show that the P460L mutation in the second fibronectin type III (FN2) domain drastically reduces EPHA1 cell surface localization while increasing tyrosine phosphorylation of the cell surface-localized receptor.

Proposal of a predictive score for the occurrence of postoperative cerebral vasospasm: analysis of a large single institution retrospective series and literature review.

Despite being uncommon, postoperative vasospasm (PoVS) present notably high morbidity and mortality rates. Our aim was to identify prognostic factors associated with this condition and introduce a scoring system to improve subsequent clinical and radiological surveillance strategies. We conducted a retrospective analysis of our institutional database covering patients aged over 18 who underwent craniotomic or transsphenoidal surgery for elective tumor removal at the Neurosurgical Unit of our institution between January 2016 and August 2023.

Eph receptor signaling complexes in the plasma membrane.

Eph receptor tyrosine kinases, together with their cell surface-anchored ephrin ligands, constitute an important cell-cell communication system that regulates physiological and pathological processes in most cell types. This review focuses on the multiple mechanisms by which Eph receptors initiate signaling via the formation of protein complexes in the plasma membrane. Upon ephrin binding, Eph receptors assemble into oligomers that can further aggregate into large complexes.

Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC.

The EphB4-ephrinB2 signaling axis has been heavily implicated in metastasis across numerous cancer types. Our emerging understanding of the dichotomous roles that EphB4 and ephrinB2 play in head and neck squamous cell carcinoma (HNSCC) poses a significant challenge to rational drug design. We find that EphB4 knockdown in cancer cells enhances metastasis in preclinical HNSCC models by augmenting immunosuppressive cells like T regulatory cells (Tregs) within the tumor microenvironment.

Reward and Inhibitory Control as Mechanisms and Treatment Targets for Binge Eating Disorder.

Purpose Of Review: Recent research has highlighted alterations in reward and inhibitory control among individuals with binge eating disorder, identifying both constructs as potential targets for treatment. Treatments targeting reward and inhibitory control for binge eating disorder are emerging. This review aims to summarize the recent literature evaluating reward and inhibitory control in binge eating disorder compared to weight-matched controls using behavioral paradigms and neuroimaging.

The pro-tumoral and anti-tumoral roles of EphA4 on T regulatory cells and tumor associated macrophages during HNSCC tumor progression.

Unlabelled: Head and Neck Squamous Cell Carcinoma (HNSCC) is a deadly cancer with poor response to targeted therapy, largely driven by an immunosuppressive tumor microenvironment (TME). Here we examine the immune-modulatory role of the receptor tyrosine kinase EphA4 in HNSCC progression. Within the TME, EphA4 is primarily expressed on regulatory T cells (Tregs) and macrophages.

Design of the FRESH-teen study: A randomized controlled trial evaluating an adapted emotion regulation weight loss program for adolescents with overweight or obesity and their parent.

Overweight and obesity affect >40% of adolescents. Family-based behavioral treatment (FBT) is the most efficacious behavioral treatment for weight management among youth and consists of nutrition and physical activity education, behavior change skills, and parent skills training. However, the efficacy of FBT decreases for youth as they get older.

Validation of a laboratory craving assessment and evaluation of 4 different interventions on cravings among adults with overweight or obesity.

Food cue reactivity (FCR) is an appetitive trait associated with overeating and weight gain. We developed a laboratory craving assessment to objectively evaluate cognitive aspects of FCR. This study examined the preliminary construct and criterion validity of this craving assessment and evaluated 4 different interventions, 2 of which incorporated cue-exposure treatment for food, on craving over treatment and follow-up.

Transmembrane helix interactions regulate oligomerization of the receptor tyrosine kinase EphA2.

The transmembrane helices of receptor tyrosine kinases (RTKs) have been proposed to switch between two different dimeric conformations, one associated with the inactive RTK and the other with the active RTK. Furthermore, recent work has demonstrated that some full-length RTKs are associated into oligomers that are larger than dimers, raising questions about the roles of the TM helices in the assembly and function of these oligomers. Here we probe the roles of the TM helices in the assembly of EphA2 RTK oligomers in the plasma membrane.

Lipidation and PEGylation Strategies to Prolong the Half-Life of a Nanomolar EphA4 Receptor Antagonist.

The EphA4 receptor tyrosine kinase plays a role in neurodegenerative diseases, inhibition of nerve regeneration, cancer progression and other diseases. Therefore, EphA4 inhibition has potential therapeutic value. Selective EphA4 kinase inhibitors are not available, but we identified peptide antagonists that inhibit ephrin ligand binding to EphA4 with high specificity.

Exploring relationships among appetitive traits, negative affect, and binge eating in adults with overweight or obesity.

Binge eating (BE) is a significant public health concern due to its prevalence and impact on mental and physical health. While research has suggested both negative affect and appetitive traits are associated with BE, few studies have investigated these constructs concurrently. Structural equation modeling (SEM) evaluated relationships between negative affect, reward-related appetitive traits, and BE among 293 adults with overweight or obesity (OW/OB) seeking treatment for BE, overeating, and weight management (m age = 46.

Inhibition of Ephrin B2 Reverse Signaling Abolishes Multiple Myeloma Pathogenesis.

Unlabelled: Bone marrow vascular endothelial cells (BM EC) regulate multiple myeloma pathogenesis. Identification of the mechanisms underlying this interaction could lead to the development of improved strategies for treating multiple myeloma. Here, we performed a transcriptomic analysis of human ECs with high capacity to promote multiple myeloma growth, revealing overexpression of the receptor tyrosine kinases, EPHB1 and EPHB4, in multiple myeloma-supportive ECs.

Identification of a muropeptide precursor transporter from gut microbiota and its role in preventing intestinal inflammation.

The gut microbiota is a considerable source of biologically active compounds that can promote intestinal homeostasis and improve immune responses. Here, we used large expression libraries of cloned metagenomic DNA to identify compounds able to sustain an anti-inflammatory reaction on host cells. Starting with a screen for NF-κB activation, we have identified overlapping clones harbouring a heterodimeric ATP-binding cassette (ABC)-transporter from a Firmicutes.

Eph receptors and ephrins in cancer progression.

Evidence implicating Eph receptor tyrosine kinases and their ephrin ligands (that together make up the 'Eph system') in cancer development and progression has been accumulating since the discovery of the first Eph receptor approximately 35 years ago. Advances in the past decade and a half have considerably increased the understanding of Eph receptor-ephrin signalling mechanisms in cancer and have uncovered intriguing new roles in cancer progression and drug resistance. This Review focuses mainly on these more recent developments.

Nongenetic Optical Modulation of Pluripotent Stem Cells Derived Cardiomyocytes Function in the Red Spectral Range.

Optical stimulation in the red/near infrared range recently gained increasing interest, as a not-invasive tool to control cardiac cell activity and repair in disease conditions. Translation of this approach to therapy is hampered by scarce efficacy and selectivity. The use of smart biocompatible materials, capable to act as local, NIR-sensitive interfaces with cardiac cells, may represent a valuable solution, capable to overcome these limitations.

Reduction in eating disorder symptoms among adults in different weight loss interventions.

Restriction of food intake and counting calories as part of weight loss programs are thought to trigger eating behaviors and attitudes which can lead to eating disorders. We have developed a treatment model, Regulation of Cues (ROC), that targets appetitive traits, including food responsiveness and satiety responsiveness, which could address overeating at an implicit level and reduce risk of detrimental behaviors and attitudes. This manuscript evaluates eating disorder symptoms, attitudes, and behaviors among adults with overweight or obesity randomized to ROC, behavioral weight loss (BWL), a combination of ROC + BWL (ROC+) and an active comparator (AC).

Functional Characterisation of the Rare p.E1225K Variant, Segregating in a Brugada Syndrome Familial Case, in Human Cardiomyocytes from Pluripotent Stem Cells.

Brugada syndrome (BrS) is an inherited autosomal dominant cardiac channelopathy. Pathogenic rare mutations in the gene, encoding the alpha-subunit of the voltage-dependent cardiac Na channel protein (Nav1.5), are identified in 20% of BrS patients, affecting the correct function of the channel.

Optical modulation of excitation-contraction coupling in human-induced pluripotent stem cell-derived cardiomyocytes.

Non-genetic photostimulation is a novel and rapidly growing multidisciplinary field that aims to induce light-sensitivity in living systems by exploiting exogeneous phototransducers. Here, we propose an intramembrane photoswitch, based on an azobenzene derivative (Ziapin2), for optical pacing of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The light-mediated stimulation process has been studied by applying several techniques to detect the effect on the cell properties.

Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations.

Mutations in the lamin A/C gene (LMNA) cause dilated cardiomyopathy associated with increased activity of ERK1/2 in the heart. We recently showed that ERK1/2 phosphorylates cofilin-1 on threonine 25 (phospho(T25)-cofilin-1) that in turn disassembles the actin cytoskeleton. Here, we show that in muscle cells carrying a cardiomyopathy-causing LMNA mutation, phospho(T25)-cofilin-1 binds to myocardin-related transcription factor A (MRTF-A) in the cytoplasm, thus preventing the stimulation of serum response factor (SRF) in the nucleus.

Psychometric properties of the Eating in the Absence of Hunger Questionnaire in treatment-seeking adults with overweight and obesity.

Understanding eating behaviors that contribute to overweight and obesity (OW/OB) is an important public health objective. One eating behavior known to contribute to overeating is eating in the absence of hunger (EAH). The Eating in the Absence of Hunger Questionnaire for Children was developed to assess external events and internal experiences that lead children to overeat.