The Three Pillars of Glioblastoma: A Systematic Review and Novel Analysis of Multi-Omics and Clinical Data.

Glioblastoma is the most fatal and common malignant brain tumor, excluding metastasis and with a median survival of approximately one year. While solid tumors benefit from newly approved drugs, immunotherapy, and prevention, none of these scenarios are opening for glioblastoma. The key to unlocking the peculiar features of glioblastoma is observing its molecular and anatomical features tightly entangled with the host's central nervous system (CNS).

A personalized osteoarthritic joint-on-a-chip as a screening platform for biological treatments.

Osteoarthritis (OA) is a highly disabling pathology, characterized by synovial inflammation and cartilage degeneration. Orthobiologics have shown promising results in OA treatment thanks to their ability to influence articular cells and modulate the inflammatory OA environment. Considering their complex mechanism of action, the development of reliable and relevant joint models appears as crucial to select the best orthobiologics for each patient.

Fusion-fission-mitophagy cycling and metabolic reprogramming coordinate nerve growth factor (NGF)-dependent neuronal differentiation.

Neuronal differentiation is regulated by nerve growth factor (NGF) and other neurotrophins. We explored the impact of NGF on mitochondrial dynamics and metabolism through time-lapse imaging, metabolomics profiling, and computer modeling studies. We show that NGF may direct differentiation by stimulating fission, thereby causing selective mitochondrial network fragmentation and mitophagy, ultimately leading to increased mitochondrial quality and respiration.

Adjusting for false discoveries in constraint-based differential metabolic flux analysis.

One of the critical steps to characterize metabolic alterations in multifactorial diseases, as well as their heterogeneity across different patients, is the identification of reactions that exhibit significantly different usage (or flux) between cohorts. However, since metabolic fluxes cannot be determined directly, researchers typically use constraint-based metabolic network models, customized on post-genomics datasets. The use of random sampling within the feasible region of metabolic networks is becoming more prevalent for comparing these networks.

Tumor heterogeneity: preclinical models, emerging technologies, and future applications.

Heterogeneity describes the differences among cancer cells within and between tumors. It refers to cancer cells describing variations in morphology, transcriptional profiles, metabolism, and metastatic potential. More recently, the field has included the characterization of the tumor immune microenvironment and the depiction of the dynamics underlying the cellular interactions promoting the tumor ecosystem evolution.

Alzheimer's Disease from the Amyloidogenic Theory to the Puzzling Crossroads between Vascular, Metabolic and Energetic Maladaptive Plasticity.

Alzheimer's disease (AD) is a progressive and degenerative disease producing the most common type of dementia worldwide. The main pathogenetic hypothesis in recent decades has been the well-known amyloidogenic hypothesis based on the involvement of two proteins in AD pathogenesis: amyloid β (Aβ) and tau. Amyloid deposition reported in all AD patients is nowadays considered an independent risk factor for cognitive decline.

Vagus Nerve Stimulation: A Personalized Therapeutic Approach for Crohn's and Other Inflammatory Bowel Diseases.

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are incurable autoimmune diseases characterized by chronic inflammation of the gastrointestinal tract. There is increasing evidence that inappropriate interaction between the enteric nervous system and central nervous system and/or low activity of the vagus nerve, which connects the enteric and central nervous systems, could play a crucial role in their pathogenesis. Therefore, it has been suggested that appropriate neuroprosthetic stimulation of the vagus nerve could lead to the modulation of the inflammation of the gastrointestinal tract and consequent long-term control of these autoimmune diseases.

Combining denoising of RNA-seq data and flux balance analysis for cluster analysis of single cells.

Background: Sophisticated methods to properly pre-process and analyze the increasing collection of single-cell RNA sequencing (scRNA-seq) data are increasingly being developed. On the contrary, the best practices to integrate these data into metabolic networks, aiming at describing metabolic phenotypes within a heterogeneous cell population, have been poorly investigated. In this regard, a critical factor is the presence of false zero values in reactions essential for a fundamental metabolic function, such as biomass or energy production.

A Comprehensive Characterization of Stemness in Cell Lines and Primary Cells of Pancreatic Ductal Adenocarcinoma.

The aim of this study is to provide a comprehensive characterization of stemness in pancreatic ductal adenocarcinoma (PDAC) cell lines. Seventeen cell lines were evaluated for the expression of cancer stem cell (CSC) markers. The two putative pancreatic CSC phenotypes were expressed heterogeneously ranging from 0 to 99.

Machine Learning for Efficient Prediction of Protein Redox Potential: The Flavoproteins Case.

Determining the redox potentials of protein cofactors and how they are influenced by their molecular neighborhoods is essential for basic research and many biotechnological applications, from biosensors and biocatalysis to bioremediation and bioelectronics. The laborious determination of redox potential with current experimental technologies pushes forward the need for computational approaches that can reliably predict it. Although current computational approaches based on quantum and molecular mechanics are accurate, their large computational costs hinder their usage.

Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a malignant prognosis. GBM is characterized by high cellular heterogeneity and its progression relies on the interaction with the central nervous system, which ensures the immune-escape and tumor promotion. This interplay induces metabolic, (epi)-genetic and molecular rewiring in both domains.

Cannabidiol Antiproliferative Effect in Triple-Negative Breast Cancer MDA-MB-231 Cells Is Modulated by Its Physical State and by IGF-1.

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has been discussed for its safety and efficacy in cancer treatments. For this reason, we have inquired into its use on triple-negative human breast cancer. Analyzing the biological effects of CBD on MDA-MB-231, we have demonstrated that both CBD dosage and serum concentrations in the culture medium influence its outcomes; furthermore, light scattering studies demonstrated that serum impacts the CBD aggregation state by acting as a surfactant agent.

Regional Development of Glioblastoma: The Anatomical Conundrum of Cancer Biology and Its Surgical Implication.

Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion.

Altered Spinal Homeostasis and Maladaptive Plasticity in GFAP Null Mice Following Peripheral Nerve Injury.

The maladaptive response of the central nervous system (CNS) following nerve injury is primarily linked to the activation of glial cells (reactive gliosis) that produce an inflammatory reaction and a wide cellular morpho-structural and functional/metabolic remodeling. Glial acidic fibrillary protein (GFAP), a major protein constituent of astrocyte intermediate filaments (IFs), is the hallmark of the reactive astrocytes, has pleiotropic functions and is significantly upregulated in the spinal cord after nerve injury. Here, we investigated the specific role of GFAP in glial reaction and maladaptive spinal cord plasticity following sciatic nerve spared nerve injury (SNI) in GFAP KO and wild-type (WT) animals.

An Optimized Workflow for the Analysis of Metabolic Fluxes in Cancer Spheroids Using Seahorse Technology.

Three-dimensional cancer models, such as spheroids, are increasingly being used to study cancer metabolism because they can better recapitulate the molecular and physiological aspects of the tumor architecture than conventional monolayer cultures. Although Agilent Seahorse XFe96 (Agilent Technologies, Santa Clara, CA, United States) is a valuable technology for studying metabolic alterations occurring in cancer cells, its application to three-dimensional cultures is still poorly optimized. We present a reliable and reproducible workflow for the Seahorse metabolic analysis of three-dimensional cultures.

Matrix metalloproteinases, purinergic signaling, and epigenetics: hubs in the spinal neuroglial network following peripheral nerve injury.

Activation of glial cells (reactive gliosis) and the purinergic pathway, together with metalloproteinase (MMP)-induced remodeling of the neural extracellular matrix (nECM), drive maladaptive changes in the spinal cord following peripheral nerve injury (PNI). We evaluated the effects on spinal maladaptive plasticity through administration of oxidized ATP (oxATP), an antagonist of P2X receptors (P2XR), and/or GM6001, an inhibitor of MMPs, in rats following spared nerve injury (SNI) of the sciatic nerve. With morpho-molecular techniques, we demonstrated a reduction in spinal reactive gliosis and changes in the neuro-glial-nECM crosstalk via expression remodeling of P2XR, nerve growth factor (NGF) receptors (TrkA and p75), and histone deacetylase 2 (HDAC2) after treatments with oxATP/GM6001.

The Spatiotemporal Coupling: Regional Energy Failure and Aberrant Proteins in Neurodegenerative Diseases.

The spatial and temporal coordination of each element is a pivotal characteristic of systems, and the central nervous system (CNS) is not an exception. Glial elements and the vascular interface have been considered more recently, together with the extracellular matrix and the immune system. However, the knowledge of the single-element configuration is not sufficient to predict physiological or pathological long-lasting changes.

GPRuler: Metabolic gene-protein-reaction rules automatic reconstruction.

Metabolic network models are increasingly being used in health care and industry. As a consequence, many tools have been released to automate their reconstruction process de novo. In order to enable gene deletion simulations and integration of gene expression data, these networks must include gene-protein-reaction (GPR) rules, which describe with a Boolean logic relationships between the gene products (e.

CGRP Inhibitors and Oxidative Stress Biomarkers in Resistant Migraine: A Real-Life Study with Erenumab, Fremanezumab, and Galcanezumab.

Patients with high-frequency resistant migraine and medication-overuse headache are still the main clinical challenge in tertiary headache centers. The approval of targeted antibodies against the calcitonin gene-related peptide (CGRP) and its receptor represents a powerful instrument. In this study, we observed how biological and clinical features of resistant migraineurs responded to erenumab, fremanezumab, or galcanezumab.

Inhibition of plasminogen/plasmin system retrieves endogenous nerve growth factor and adaptive spinal synaptic plasticity following peripheral nerve injury.

Dysfunctions of the neuronal-glial crosstalk and/or impaired signaling of neurotrophic factors represent key features of the maladaptive changes in the central nervous system (CNS) in neuroinflammatory as neurodegenerative disorders. Tissue plasminogen activator (tPA)/plasminogen (PA)/plasmin system has been involved in either process of maturation and degradation of nerve growth factor (NGF), highlighting multiple potential targets for new therapeutic strategies. We here investigated the role of intrathecal (i.

The Glioblastoma Microenvironment: Morphology, Metabolism, and Molecular Signature of Glial Dynamics to Discover Metabolic Rewiring Sequence.

Different functional states determine glioblastoma (GBM) heterogeneity. Brain cancer cells coexist with the glial cells in a functional syncytium based on a continuous metabolic rewiring. However, standard glioma therapies do not account for the effects of the glial cells within the tumor microenvironment.