Digital Image Analysis Applied to Tumor Cell Proliferation, Aggressiveness, and Migration-Related Protein Synthesis in Neuroblastoma 3D Models.

Patient-derived cancer 3D models are a promising tool that will revolutionize personalized cancer therapy but that require previous knowledge of optimal cell growth conditions and the most advantageous parameters to evaluate biomimetic relevance and monitor therapy efficacy. This study aims to establish general guidelines on 3D model characterization phenomena, focusing on neuroblastoma. We generated gelatin-based scaffolds with different stiffness and performed SK-N-BE(2) and SH-SY5Y aggressive neuroblastoma cell cultures, also performing co-cultures with mouse stromal Schwann cell line (SW10).

Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes.

Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles from 127 HR-NB patients: (1) Copy number aberration burden (%gains+%losses), (2) copy number load (CNL) (%gains-%losses) and (3) net genomic load (NGL) (%gains-%losses).

PPAR gamma agonist leriglitazone improves frataxin-loss impairments in cellular and animal models of Friedreich Ataxia.

Friedreich ataxia (FRDA), the most common autosomal recessive ataxia, is characterized by degeneration of the large sensory neurons and spinocerebellar tracts, cardiomyopathy, and increased incidence in diabetes. The underlying pathophysiological mechanism of FRDA, driven by a significantly decreased expression of frataxin (FXN), involves increased oxidative stress, reduced activity of enzymes containing iron‑sulfur clusters (ISC), defective energy production, calcium dyshomeostasis, and impaired mitochondrial biogenesis, leading to mitochondrial dysfunction. The peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcriptional factor playing a key role in mitochondrial function and biogenesis, fatty acid storage, energy metabolism, and antioxidant defence.

Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model.

Friedreich ataxia (FRDA) is a neurodegenerative disorder characterized by neuromuscular and neurological manifestations. It is caused by mutations in the FXN gene, which results in loss of the mitochondrial protein frataxin. Endoplasmic Reticulum-mitochondria associated membranes (MAMs) are inter-organelle structures involved in the regulation of essential cellular processes, including lipid metabolism and calcium signaling.

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line.

Background: Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible.

Potential Molecular Players of the Tumor Microenvironment in Extracranial Pediatric Solid Tumors.

Pediatric cancers are rare malignancies worldwide and represent around 1% of all new cancer diagnoses. (..

Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures.

A number of aging-related disorders (ARD) have been related to oxidative stress (OS) and mitochondrial dysfunction (MDF) in a well-established body of literature. Most studies focused on cardiovascular disorders (CVD), type 2 diabetes (T2D), and neurodegenerative disorders. Counteracting OS and MDF has been envisaged to improve the clinical management of ARD, and major roles have been assigned to three mitochondrial cofactors, also termed mitochondrial nutrients (MNs), i.

Adverse events associated with the use of recommended vaccines during pregnancy: An overview of systematic reviews.

Introduction: Maternal immunization is aimed at reducing morbidity and mortality in pregnant women and their newborns. Updated evidence synthesis of maternal-fetal outcomes is constantly needed to ensure that the risk-benefit of vaccination during pregnancy remains positive.

Methods: An overview of systematic reviews (OoSRs) was performed.

11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma.

High-risk neuroblastomas typically display an undifferentiated or poorly differentiated morphology. It is therefore vital to understand molecular mechanisms that block the differentiation process. We identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in the maintenance of undifferentiated neural crest-derived progenitors through the repression of DLG2, a candidate tumor suppressor gene in neuroblastoma.

Friedreich Ataxia: current state-of-the-art, and future prospects for mitochondrial-focused therapies.

Friedreich's Ataxia is an autosomal recessive genetic disease causing the defective gene product, frataxin. A body of literature has been focused on the attempts to counteract frataxin deficiency and the consequent iron imbalance, in order to mitigate the disease-associated pro-oxidant state and clinical course. The present mini review is aimed at evaluating the basic and clinical reports on the roles and the use of a set of iron chelators, antioxidants and some cofactors involved in the key mitochondrial functions.

Citation impact was highly variable for reporting guidelines of health research: a citation analysis.

Objectives: Over 400 reporting guidelines are currently published, but the frequency of their use by authors to accurately and transparently report research remains unclear. This study examined citation counts of reporting guidelines and characteristics contributing to their citation impact.

Study Design And Setting: Web of Science database was searched for citation counts of all reporting guidelines with a minimum citation age of 5 years.

Optimized NGS Approach for Detection of Aneuploidies and Mosaicism in PGT-A and Imbalances in PGT-SR.

The detection of chromosomal aneuploidies and mosaicism degree in preimplantation embryos may be essential for achieving pregnancy. The aim of this study was to determine the robustness of diagnosing homogenous and mosaic aneuploidies using a validated algorithm and the minimal resolution for de novo and inherited deletions and duplications (Del/Dup). Two workflows were developed and validated: (a,b) preimplantation genetic testing for uniform whole and segmental aneuploidies, plus mixtures of euploid/aneuploid genomic DNA to develop an algorithm for detecting mosaicism; and (c) preimplantation genetic testing for structural rearrangements for detecting Del/Dup ≥ 6 Mb.

Integrating the Tumor Microenvironment into Cancer Therapy.

Tumor progression is mediated by reciprocal interaction between tumor cells and their surrounding tumor microenvironment (TME), which among other factors encompasses the extracellular milieu, immune cells, fibroblasts, and the vascular system. However, the complexity of cancer goes beyond the local interaction of tumor cells with their microenvironment. We are on the path to understanding cancer from a systemic viewpoint where the host macroenvironment also plays a crucial role in determining tumor progression.

A three-dimensional bioprinted model to evaluate the effect of stiffness on neuroblastoma cell cluster dynamics and behavior.

Three-dimensional (3D) bioprinted culture systems allow to accurately control microenvironment components and analyze their effects at cellular and tissue levels. The main objective of this study was to identify, quantify and localize the effects of physical-chemical communication signals between tumor cells and the surrounding biomaterial stiffness over time, defining how aggressiveness increases in SK-N-BE(2) neuroblastoma (NB) cell line. Biomimetic hydrogels with SK-N-BE(2) cells, methacrylated gelatin and increasing concentrations of methacrylated alginate (AlgMA 0%, 1% and 2%) were used.

Cofilin dysregulation alters actin turnover in frataxin-deficient neurons.

Abnormalities in actin cytoskeleton have been linked to Friedreich's ataxia (FRDA), an inherited peripheral neuropathy characterised by an early loss of neurons in dorsal root ganglia (DRG) among other clinical symptoms. Despite all efforts to date, we still do not fully understand the molecular events that contribute to the lack of sensory neurons in FRDA. We studied the adult neuronal growth cone (GC) at the cellular and molecular level to decipher the connection between frataxin and actin cytoskeleton in DRG neurons of the well-characterised YG8R Friedreich's ataxia mouse model.

Reporting guidelines of health research studies are frequently used inappropriately.

Objectives: Appropriate use of reporting guidelines of health research ensures that articles present readers with a consistent representation of study relevance, methodology, and results. This study evaluated the use of major reporting guidelines.

Study Design And Setting: A cross-sectional analysis of health research articles citing four major reporting guidelines indexed in the Web of Science Core Collection (up to June 24, 2018).

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders.

Recent observations related to the structure of the cytoskeleton in neurons and novel cytoskeletal abnormalities involved in the pathophysiology of some neurological diseases are changing our view on the function of the cytoskeletal proteins in the nervous system. These efforts allow a better understanding of the molecular mechanisms underlying neurological diseases and allow us to see beyond our current knowledge for the development of new treatments. The neuronal cytoskeleton can be described as an organelle formed by the three-dimensional lattice of the three main families of filaments: actin filaments, microtubules, and neurofilaments.

Oxygen in the neonatal period: Oxidative stress, oxygen load and epigenetic changes.

Preterm infants frequently require positive pressure ventilation and oxygen supplementation in the first minutes after birth. It has been shown that the amount of oxygen provided during stabilization, the oxygen load, if excessive may cause hyperoxia, and oxidative damage to DNA. Epidemiologic studies have associated supplementation with pure oxygen in the first minutes after birth with childhood cancer.

Mitoprotective Clinical Strategies in Type 2 Diabetes and Fanconi Anemia Patients: Suggestions for Clinical Management of Mitochondrial Dysfunction.

Oxidative stress (OS) and mitochondrial dysfunction (MDF) occur in a number of disorders, and several clinical studies have attempted to counteract OS and MDF by providing adjuvant treatments against disease progression. The present review is aimed at focusing on two apparently distant diseases, namely type 2 diabetes (T2D) and a rare genetic disease, Fanconi anemia (FA). The pathogenetic links between T2D and FA include the high T2D prevalence among FA patients and the recognized evidence for OS and MDF in both disorders.

Mu Opioid Receptor 1 (MOR-1) Expression in Colorectal Cancer and Oncological Long-Term Outcomes: A Five-Year Retrospective Longitudinal Cohort Study.

Preclinical evidence has shown increased expression of mu opioid receptor 1 (MOR-1) in colorectal cancer although its association with disease-free and overall survival (DFS and OS) has not been investigated. We hypothesized that MOR-1 was overexpressed in tumor samples compared to normal tissue and this was associated with decreased DFS and OS. We carried out a retrospective study assessing the association of MOR-1 tumor expression with long-term outcomes by immunohistochemistry in normal and tumor samples from 174 colorectal cancer patients.

Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis.

Background: Randomised controlled trials (RCTs) provide the most reliable information to inform clinical practice and patient care. We aimed to map global clinical research publication activity through RCT-related articles in high-impact-factor medical journals over the past five decades.

Methods: We conducted a cross-sectional analysis of articles published in the highest ranked medical journals with an impact factor > 10 (according to Journal Citation Reports published in 2017).

The tumour microenvironment as an integrated framework to understand cancer biology.

Cancer cells all share the feature of being immersed in a complex environment with altered cell-cell/cell-extracellular element communication, physicochemical information, and tissue functions. The so-called tumour microenvironment (TME) is becoming recognised as a key factor in the genesis, progression and treatment of cancer lesions. Beyond genetic mutations, the existence of a malignant microenvironment forms the basis for a new perspective in cancer biology where connections at the system level are fundamental.

Prevalence and comorbidity of autism spectrum disorder in Spain: study protocol for a systematic review and meta-analysis of observational studies.

Background: Autism spectrum disorder (ASD) is a complex developmental disorder characterised by impaired social interaction and communication, and restrictive and repetitive behaviour. Previous systematic reviews have traditionally assessed the prevalence of ASD on global or regional context, with very few meta-analyses at the country level. The objective of this study will be to systematically evaluate published and unpublished observational studies that present prevalence and comorbidity of ASD among children, adolescent and adult population in Spain.