Glutaminase-2 Expression Induces Metabolic Changes and Regulates Pyruvate Dehydrogenase Activity in Glioblastoma Cells.

Glutaminase controls the first step in glutaminolysis, impacting bioenergetics, biosynthesis and oxidative stress. Two isoenzymes exist in humans, GLS and GLS2. GLS is considered prooncogenic and overexpressed in many tumours, while GLS2 may act as prooncogenic or as a tumour suppressor.

Molecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression.

Prostate cancer (PCa) remains a critical global health challenge, with high mortality rates and significant heterogeneity, particularly in advanced stages. While early-stage PCa is often manageable with conventional treatments, metastatic PCa is notoriously resistant, highlighting an urgent need for precise biomarkers and innovative therapeutic strategies. This review focuses on the dualistic roles of sirtuins, a family of NAD+-dependent histone deacetylases, dissecting their unique contributions to tumor suppression or progression in PCa depending on the cellular context.

Adopting GPR75 in treating obesity: unraveling the knowns and unknowns of this orphan GPCR.

G protein-coupled receptor 75 (GPR75) is emerging as a promising target for obesity treatment, but its exact role in energy regulation remains unclear. This article explores the latest research on GPR75's molecular function, potential ligands, and therapeutic challenges in addressing obesity.

Exploring in vivo human brain metabolism at 10.5 T: Initial insights from MR spectroscopic imaging.

Introduction: Ultra-high-field magnetic resonance (MR) systems (7 T and 9.4 T) offer the ability to probe human brain metabolism with enhanced precision. Here, we present the preliminary findings from 3D MR spectroscopic imaging (MRSI) of the human brain conducted with the world's first 10.

Intraoperative Anesthetic Care During Emergent/Urgent Craniotomy or Craniectomy for Intracranial Hypertension or Herniation: A Systematic Review.

This systematic review aimed to identify and describe best practice for the intraoperative anesthetic management of patients undergoing emergent/urgent decompressive craniotomy or craniectomy for any indication. The PubMed, Scopus, EMBASE, and Cochrane databases were searched for articles related to urgent/emergent craniotomy/craniectomy for intracranial hypertension or brain herniation. Only articles focusing on intraoperative anesthetic management were included; those investigating surgical or intensive care unit management were excluded.

A lever hypothesis for Synaptotagmin-1 action in neurotransmitter release.

Neurotransmitter release is triggered in microseconds by Ca-binding to the Synaptotagmin-1 C-domains and by SNARE complexes that form four-helix bundles between synaptic vesicles and plasma membranes, but the coupling mechanism between Ca-sensing and membrane fusion is unknown. Release requires extension of SNARE helices into juxtamembrane linkers that precede transmembrane regions (linker zippering) and binding of the Synaptotagmin-1 CB domain to SNARE complexes through a "primary interface" comprising two regions (I and II). The Synaptotagmin-1 Ca-binding loops were believed to accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers, or helping bridge the membranes, but SNARE complex binding through the primary interface orients the Ca-binding loops away from the fusion site, hindering these putative activities.

Morphogen-induced kinase condensates transduce Hh signal by allosterically activating Gli.

Hedgehog (Hh) morphogen governs embryonic development and tissue homeostasis through the Ci/Gli family transcription factors. Here we report that Hh induces phase separation of the fused (Fu)/Ulk family kinases to allosterically regulate Ci/Gli. We find that Hh-induced phosphorylation of Fu/Ulk3 promotes SUMOylation of their inverted phosphorylation-dependent SUMOylation motifs.

Obesity reshapes regulatory T cells in the visceral adipose tissue by disrupting cellular cholesterol homeostasis.

Regulatory T cells (T) accumulate in the visceral adipose tissue (VAT) to maintain systemic metabolic homeostasis but decline during obesity. Here, we explored the metabolic pathways controlling the homeostasis, composition, and function of VAT T under normal and high-fat diet feeding conditions. We found that cholesterol metabolism was specifically up-regulated in ST2 VAT T subsets.

Associations of Central Arterial Stiffness With Brain White Matter Integrity and Gray Matter Volume in MRI Across the Adult Lifespan.

Background: Central arterial stiffening is associated with brain white matter (WM) damage and gray matter (GM) volume loss in older adults, but little is known about this association from an adult lifespan perspective.

Purpose: To investigate the associations of central arterial stiffness with WM microstructural organization, WM lesion load, cortical thickness, and GM volume in healthy adults across the lifespan.

Study Type: This is a cross-sectional study.

The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis.

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear.

Inhibition of Unc-51-like-kinase is mitoprotective during infection in corneal epithelial cells.

(PA) is an opportunistic gram-negative pathogen that can infect the cornea, leading to permanent vision loss. Autophagy is a cannibalistic process that drives cytoplasmic components to the lysosome for degradation and/or recycling. Autophagy has been shown to play a key role in the removal of intracellular pathogens and, as such, is an important component of the innate immune response.

Metabolomics-Driven Biomarker Discovery for Breast Cancer Prognosis and Diagnosis.

Breast cancer is a cancer with global prevalence and a surge in the number of cases with each passing year. With the advancement in science and technology, significant progress has been achieved in the prevention and treatment of breast cancer to make ends meet. The scientific intradisciplinary subject of "metabolomics" examines every metabolite found in a cell, tissue, system, or organism from different sources of samples.

Coronary atherosclerosis in athletes: emerging concepts and preventive strategies.

There should be no assumption that an athlete is immune to coronary artery disease (CAD), even when traditional cardiovascular (CV) risk factors appear well-managed. Excelling in certain aspects of health does not equate to total CV protection. Recent data from cardiac imaging studies have raised the possibility that long-term, high-volume, high-intensity endurance exercise is associated with coronary atherosclerosis.

Mechanical Circulatory Support in Patients Without Cardiogenic Shock Undergoing Percutaneous Coronary Intervention.

Background: The use of mechanical circulatory support devices for high-risk percutaneous coronary intervention (PCI) has increased over the past decade despite limited data of benefit. We sought to examine the association between intravascular microaxial left ventricular assist device (LVAD) versus intra-aortic balloon pump use in patients without cardiogenic shock (CS) undergoing PCI.

Methods And Results: This retrospective study analyzed claims data from a large, insured population who underwent PCI without CS from April 1, 2016 to July 31, 2022.

A pan-tumor review of the role of poly(adenosine diphosphate ribose) polymerase inhibitors.

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications.

The Melody Valve in Small Children Undergoing First Mitral Valve Replacement: Better Than Mechanical?

Background: In small children with left atrioventricular valve dysfunction, valve repair is preferred but some will require valve replacement. No prosthetic valve has growth potential, bioprostheses have poor durability, and mechanical prostheses have high rates of thromboembolic and hemorrhagic complications. We reviewed our experience with a modified bovine jugular vein valve designed for use in the right ventricular outflow tract (Melody valve, Medtronic) and compared this with contemporary mechanical valve replacement.

Non-Caucasian Race/Ethnicity Predisposes to Unfavorable Stage and Grade at Upper Tract Urothelial Carcinoma Diagnosis.

Objective: To test whether race/ethnicity affects stage or grade distribution at upper tract urothelial carcinoma (UTUC) diagnosis.

Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database 2004-2020, UTUC patients were identified. Multivariable logistic regression models tested for the association between race/ethnicity and stage as well as grade at diagnosis according to renal pelvis vs.

Impact of population screening for Lynch syndrome insights from the All of Us data.

Lynch Syndrome (LS) is a common genetic cancer condition that allows for personalized cancer prevention and early cancer detection in identified gene carriers. We used data from the All of Us (AOU) Research Initiative to assess the prevalence of LS in the general U.S.

Joint k-b space diffusion-weighted image reconstruction and apparent diffusion coefficient fitting for diffusion-weighted turbo-spin-echo imaging.

Background: Diffusion-weighted (DW) turbo-spin-echo (TSE) imaging offers improved geometric fidelity compared to single-shot echo-planar-imaging (EPI). However, it suffers from low signal-to-noise ratio (SNR) and prolonged acquisition times, thereby restricting its applications in diagnosis and MRI-guided radiotherapy (MRgRT).

Purpose: To develop a joint k-b space reconstruction algorithm for concurrent reconstruction of DW-TSE images and the apparent diffusion coefficient (ADC) map with enhanced image quality and more accurate quantitative measurements.

Dysregulation of Airway and Systemic Interferon Responses Promote Asthma Exacerbations in Urban Children.

Background: Determining why some upper respiratory illnesses provoke asthma exacerbations remains an unmet need.

Objective: To identify transcriptome-wide gene expression changes associated with colds that progress to exacerbation.

Methods: 208 urban children (6-17 years) with exacerbation-prone asthma were prospectively monitored for up to two cold illnesses.

Contour uncertainty assessment for MD-omitted daily adaptive online head and neck radiotherapy.

Background And Purpose: Daily online adaptive radiotherapy (DART) increases treatment accuracy by crafting daily customized plans that adjust to the patient's daily setup and anatomy. The routine application of DART is limited by its resource-intensive processes. This study proposes a novel DART strategy for head and neck squamous cell carcinoma (HNSCC), automizing the process by propagating physician-edited treatment contours for each fraction.

DNA damage and its links to neuronal aging and degeneration.

DNA damage is a major risk factor for the decline of neuronal functions with age and in neurodegenerative diseases. While how DNA damage causes neurodegeneration is still being investigated, innovations over the past decade have provided significant insights into this issue. Breakthroughs in next-generation sequencing methods have begun to reveal the characteristics of neuronal DNA damage hotspots and the causes of DNA damage.

Sleep Deprivation Elevates Resting and Exercise Blood Pressures and Augments Pressor Response at Exercise Onset.

Purpose: Sleep deprivation and elevated blood pressure (BP) increase the risk of cardiovascular diseases. However, the effects of sleep deprivation on BP response, especially at exercise onset remain unclear. We aimed to elucidate the effects of experimental sleep deprivation (ESD) on resting and exercise BPs, including that at exercise onset, and investigate whether a night-time nap during ESD changes the ESD-altered BP.