Hormonal Regulation of Urokinase- and Tissue-Type Plasminogen Activator in Mouse Sertoli Cells.

A role for the plasminogen activator (PA) system has been postulated in mammalian gonads, considering the complex process of morphogenesis these organs undergo during their development. Our results show that mouse Sertoli cells under basal conditions produce both types of PA, tissue-type PA (tPA) and urokinase-type PA (uPA), and hormonal treatments increase the production of both enzymes. The increased enzyme secretion does not correlate with a parallel increase in their mRNAs.

Extracorporeal membrane oxygenation in trauma: a single-center retrospective observational study.

Purpose: Globally, trauma is a leading cause of death in young adults. The use of extracorporeal membrane oxygenation (ECMO) in the trauma population remains controversial due to the limited published research. This study aimed to analyze 30-day survival of all the trauma ECMO patients at our center, with respect to injury severity score (ISS) and new injury severity score (NISS).

The effect of maternal risk factors during pregnancy on children's motor development at 5-6 years.

Background And Aims: Maternal diet and health may influence a child's later neurodevelopment. We investigated the effect of maternal diet, adiposity, gestational diabetes mellitus (GDM), and depressive/anxiety symptoms during pregnancy on the child's motor outcome at 5-6 years.

Methods: The motor performance of 159 children of women with overweight or obesity (pre-pregnancy body mass index 25-29.

Spatio-temporal transformers for decoding neural movement control.

Deep learning tools applied to high-resolution neurophysiological data have significantly progressed, offering enhanced decoding, real-time processing, and readability for practical applications. However, the design of artificial neural networks to analyze neural activity in vivo remains a challenge, requiring a delicate balance between efficiency in low-data regimes and the interpretability of the results. Approach: To address this challenge, we introduce a novel specialized transformer architecture to analyze single-neuron spiking activity.

Trithorax regulates long-term memory in Drosophila through epigenetic maintenance of mushroom body metabolic state and translation capacity.

The role of epigenetics and chromatin in the maintenance of postmitotic neuronal cell identities is not well understood. Here, we show that the histone methyltransferase Trithorax (Trx) is required in postmitotic memory neurons of the Drosophila mushroom body (MB) to enable their capacity for long-term memory (LTM), but not short-term memory (STM). Using MB-specific RNA-, ChIP-, and ATAC-sequencing, we find that Trx maintains homeostatic expression of several non-canonical MB-enriched transcripts, including the orphan nuclear receptor Hr51, and the metabolic enzyme lactate dehydrogenase (Ldh).

Increased plugging latency in cycling epiERα-/- (Esr1f/-Wnt7aCre/+) mice.

Wnt7a-Cre is a commonly used for generating uterine epithelial conditional knockout mice, such as epiERα-/- (Esr1f/-Wnt7aCre/+) and epiPR-/- (Pgrf/-Wnt7aCre/+). We noticed that epiERα-/- females, but not epiPR-/- females, have prolonged plugging latency, which is the duration between continuous cohabitation and detection of the first vaginal plug (a sign of mating). Mating occurs in proestrus and/or estrus stages of the estrous cycle.

Mechanistic insights on lycopene usage against diabetes and associated complications.

Lycopene is a tetraterpene compound belonging to carotenoids that are widely present in tomatoes and similar products. It is known as a powerful anti-oxidant and a non-provitamin A carotenoid. Lycopene has been found to effectively improve diabetes mellitus and its complications, such as cardiac complications, disorders caused by oxidative stress, and liver and neurological disorders.

Nutraceutical Impact of Pumpkin Seed Oil on Expression Levels of EZH-2 and KRT-14 Genes against DSS-induced Inflammatory Bowel Disease in the Rat Model.

Inflammatory bowel disease is a collection of intestinal disorders that cause inflammation in the digestive tract. Prolonged inflammation in the gastrointestinal tract is a major risk factor for colorectal cancer. The objective of this study was to fucus on gene expression levels of (KRT-14; associated with epithelial cell integrity) and enhancer of zeste homolog-1 (EZH-2; involved in cellular proliferation) in a IBD rat model in order to rule out impact of nutraceuticals (pumpkin seed oil; PSO) as a complementary approach to conventional treatments of IBD.

Atovaquone and Selinexor as a Novel Combination Treatment Option in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common acute leukemia and is predominantly affecting older patients. It is a heterogenous disease, showing a broad spectrum of genomic alterations and mutations that influence the clinical outcome and treatment options. The expression of the signal transducer and activator of transcription 3 (STAT3) is often dysregulated in AML and its constitutive activation is associated with poor outcome.

Multidimensional library for the improved identification of per- and polyfluoroalkyl substances (PFAS).

As the occurrence of human diseases and conditions increase, questions continue to arise about their linkages to chemical exposure, especially for per-and polyfluoroalkyl substances (PFAS). Currently, many chemicals of concern have limited experimental information available for their use in analytical assessments. Here, we aim to increase this knowledge by providing the scientific community with multidimensional characteristics for 175 PFAS and their resulting 281 ion types.

Cashew nut consumption reduces waist circumference and oxidative stress in adolescents with obesity: A randomized clinical trial.

Previous evidence suggests that certain types of nuts, when included in a healthy diet pattern, may provide health benefits. Therefore, we hypothesize that the consumption of cashew nuts associated with a healthy diet may enhance antioxidant defenses and improve anthropometric and body composition parameters in individuals with obesity. We conducted a 12-week randomized clinical trial, divided into 4 sessions, involving adolescents randomly assigned to receive either 30 g of roasted cashew nuts together with nutrition education (cashew nut group-CNG) or only nutrition education (control group-CG).

Lupeol Attenuates Palmitate-Induced Hypertrophy in 3T3-L1 Adipocytes.

Obesity is characterized by the enlargement of adipose tissue due to an increased calorie intake exceeding the body's energy expenditure. Changes in the size of adipose tissue can lead to harmful consequences, with excessive fat accumulation resulting in adipocyte hypertrophy and promoting metabolic dysfunction. These adiposity-associated pathologies can be influenced by dietary components and their potential health benefits.

Unseen Enemy: Mechanisms of Multidrug Antimicrobial Resistance in Gram-Negative ESKAPE Pathogens.

Multidrug antimicrobial resistance (AMR) represents a formidable challenge in the therapy of infectious diseases, triggered by the particularly concerning gram-negative , , , , , and spp. (ESKAPE) pathogens. Designated as a "priority" in 2017, these bacteria continue to pose a significant threat in 2024, particularly during the worldwide SARS-CoV-2 pandemic, where coinfections with ESKAPE members contributed to worsened patient outcomes.

Activation of Genes by Nuclear Receptor/Specificity Protein (Sp) Interactions in Cancer.

The human nuclear receptor (NR) superfamily consists of 48 genes that are ligand-activated transcription factors that play a key role in maintaining cellular homeostasis and in pathophysiology. NRs are important drug targets for both cancer and non-cancer endpoints as ligands for these receptors can act as agonists, antagonists or inverse agonists to modulate gene expression. With two exceptions, the classical mechanism of action of NRs involves their interactions as monomers, dimers or heterodimers with their cognate response elements (cis-elements) in target gene promoters.

Normothermic Crystalloid Polarizing Cardioplegia Improves Systolic and Diastolic Function in a Porcine Model of Cardiopulmonary Bypass.

Previously, we showed that blood-based polarizing cardioplegia exerted beneficial cardioprotection during hypothermic ischemia; however, these positive effects of blood-based polarizing cardioplegia were reduced during normothermic ischemia compared to blood-based hyperkalemic (depolarizing) cardioplegia. This study compares crystalloid polarizing cardioplegia to crystalloid depolarizing cardioplegia in a normothermic porcine model of cardiopulmonary bypass; Methods: Twelve pigs were randomized to receive either normothermic polarizing ( = 7) or depolarizing ( = 5) crystalloid cardioplegia. After the initiation of cardiopulmonary bypass, normothermic arrest (34 °C, 60 min) was followed by 60 min of on-pump and 90 min of off-pump reperfusion.

Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3).

Derivation of human toxicokinetic parameters and internal threshold of toxicological concern for tenuazonic acid through a human intervention trial and hierarchical Bayesian population modeling.

Background: Tenuazonic acid (TeA), a mycotoxin produced by Alternaria alternata, contaminates various food commodities and is known to cause acute and chronic health effects. However, the lack of human toxicokinetic (TK) data and the reliance on external exposure estimates have stalled a comprehensive risk assessment for TeA.

Objective: To bridge this gap, a human TK trial and population-based TK (PopTK) modeling were applied to determine human TK parameters of TeA, and the results were applied for risk screening using population biomonitoring data and threshold of toxicological concern (TTC)-based approaches.

KLRB1 expression in nasopharyngeal mucosa as a prognostic biomarker in COVID-19 patients.

The resurgence of COVID-19 and the rise in severe outcomes emphasize the need for reliable prognostic markers to guide patient care and optimize ICU and hospital resources. This study investigates the potential of nasopharyngeal swabs to identify biomarkers that predict ICU admission or death in hospitalized COVID-19 patients. We analyzed nasopharyngeal exudates from 95 hospitalized patients in 2020 using high-plex RNA quantification on the NanoString nCounter platform.

Resting-state electroencephalographic rhythms depend on sex in patients with dementia due to Parkinson's and Lewy Body diseases: An exploratory study.

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are more prevalent in males than females. Furthermore, they typically showed abnormally high delta (< 4 Hz) and low alpha (8-10 Hz) rhythms from resting-state electroencephalographic (rsEEG) activity. Here, we hypothesized that those abnormalities may depend on the patient's sex.

Optimizing TMS dosimetry: evaluating the effective electric field as a novel metric.

Objective: This study introduces the effective electric field (Eeff) as a novel observable for transcranial magnetic stimulation (TMS) numerical dosimetry. Eeff represents the electric field component aligned with the local orientation of cortical and white matter neuronal elements. To assess the utility of Eeff as a predictive measure for TMS outcomes, we evaluated its correlation with TMS induced muscle responses and compared it against conventional observables, including the electric (E-)field magnitude, and its components normal and tangential to the cortical surface.

Fixed dosing of alpelisib for children with vascular anomalies: Can we do better?

Severe forms of vascular malformations (VM) can highly impact patients' quality of life and lead to life-threatening organ dysfunction. Numerous VM are caused by somatic activating mutations in the PI3K/AKT/mTOR signalling pathway. Alpelisib, a PIK3CA inhibitor was recently FDA-approved for paediatric PIK3CA-related overgrowth syndrome (PROS).

The Dynamicity of the Oxytocin Receptor in the Brain May Trigger Sensory Deficits in Autism Spectrum Disorder.

Sensory processing abnormalities have been noted since the first clinical description of autism in 1940. However, it was not until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 that sensory challenges were considered as symptoms of autism spectrum disorder (ASD). Multisensory processing is of paramount importance in building a perceptual and cognitive representation of reality.

Valproate-Induced Model of Autism in Adult Zebrafish: A Systematic Review.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social skills and the presence of repetitive and restricted behaviors and interests. The social behavior of the zebrafish (Danio rerio) makes this organism a valuable tool for modeling ASD in order to explore the social impairment typical of this disorder. In addition to transgenic models, exposure of zebrafish embryos to valproic acid (VPA) has been found to produce ASD-like symptoms.

Repurposing the prostaglandin analogue treprostinil and the calcium-sensing receptor modulator cinacalcet to revive cord blood as an alternate source of hematopoietic stem and progenitor cells for transplantation.

Objective: The expanding field of hematopoietic cell transplantation (HCT) for non-malignant diseases, including those amenable to gene therapy or gene editing, faces challenges due to limited donor availability and the toxicity associated with cell collection methods. Umbilical cord blood (CB) represents a readily accessible source of hematopoietic stem and progenitor cells (HSPCs); however, the cell dose obtainable from a single cord blood unit is frequently insufficient. This limitation can be addressed by enhancing the potency of HSPCs, specifically their capacity to reconstitute hematopoiesis.