95 results match your criteria: "Mario Negri Institute for Pharmacological Research (IRCCS)[Affiliation]"

Inflammation and depression: A study protocol to dissect pathogenetic mechanisms in the onset, comorbidity and treatment response.

Brain Behav Immun Health

December 2024

Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Article Synopsis
  • * The study, funded by the Italian Ministry of Health, aims to explore how inflammation contributes to depression onset, treatment resistance, and related health issues through various scientific analyses and human cohorts.
  • * Over two years, the research will enhance understanding of inflammation's role in MDD and related disorders, potentially leading to new personalized treatment strategies.
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Implants versus autologous tissue flaps for breast reconstruction following mastectomy.

Cochrane Database Syst Rev

October 2024

G.Re.T.A. Group for Reconstructive and Therapeutic Advancements, Milan, Italy.

Background: Women who have a mastectomy for breast cancer treatment or risk reduction may be offered different options for breast reconstruction, including use of implants or the woman's own tissue (autologous tissue flaps). The choice of technique depends on factors such as the woman's preferences, breast characteristics, preoperative imaging, comorbidities, smoking habits, prior chest or breast irradiation, and planned adjuvant therapies.

Objectives: To assess the effects of implants versus autologous tissue flaps for postmastectomy breast reconstruction on women's quality of life, satisfaction, and short- and long-term surgical complications.

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In the past decade, significant European calls for research proposals have supported translational collaborative research on non-communicable and infectious diseases within the biomedical life sciences by bringing together interdisciplinary and multinational consortia. This research has advanced our understanding of disease pathophysiology, marking considerable scientific progress. Yet, it is crucial to retrospectively evaluate these efforts' societal impact.

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How to Test for Predicting Resistance to Anti-Epidermal Growth Factor Receptor Therapy in Metastatic Colorectal Cancer? Evidence From the Secondary Analysis of Biomarkers of CALGB/SWOG 80405.

J Clin Oncol

October 2024

Andrea Sartore-Bianchi, MD, Department of Hematology Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy, Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy; Silvia Marsoni, MD, IFOM ETS-The AIRC Institute of Molecular Oncology, Milan, Italy; Alessio Amatu, MD, Department of Hematology Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Valter Torri, MD, Department of Clinical Oncology, "Mario Negri" Institute for Pharmacological Research- IRCCS, Milan, Italy; Emanuela Bonoldi, MD, Department of Hematology Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Alberto Bardelli, PhD, IFOM ETS-The AIRC Institute of Molecular Oncology, Milan, Italy, Department of Oncology, Università degli Studi di Torino, Turin, Italy; Livio Trusolino, MD, Department of Oncology, Università degli Studi di Torino, Turin, Italy, Laboratory of Translational Cancer Medicine, Candiolo Cancer Institute-FPO IRCCS, Turin, Italy; Salvatore Siena, MD, Department of Hematology Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy, Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy.

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Onvansertib treatment overcomes olaparib resistance in high-grade ovarian carcinomas.

Cell Death Dis

July 2024

Laboratory of Preclinical Gynecological Oncology, Experimental Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Occurrence of resistance to olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) approved in ovarian carcinoma, has already been shown in clinical settings. Identifying combination treatments to sensitize tumor cells and/or overcome resistance to olaparib is critical. Polo-like kinase 1 (PLK1), a master regulator of mitosis, is also involved in the DNA damage response promoting homologous recombination (HR)-mediated DNA repair and in the recovery from the G2/M checkpoint.

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Introduction: In patients admitted to intensive care units (ICUs), Gram-negative bacteria (GNB) infections pose significant challenges due to their contribution to morbidity, mortality, and healthcare costs. During the SARS-CoV-2 pandemic, Italy witnessed a rise in healthcare-associated infections (HAIs), with GNBs involved in a substantial proportion of cases. Concerningly, carbapenem-resistant GNBs (CR-GNBs) have increased worldwide, posing therapeutic challenges.

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In ovarian tumors, the omental microenvironment profoundly influences the behavior of cancer cells and sustains the acquisition of stem-like traits, with major impacts on tumor aggressiveness and relapse. Here, we leverage a patient-derived platform of organotypic cultures to study the crosstalk between the tumor microenvironment and ovarian cancer stem cells. We discovered that the pro-tumorigenic transcription factor FOXM1 is specifically induced by the microenvironment in ovarian cancer stem cells, through activation of FAK/YAP signaling.

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Crystal structure of archaeal IF5A-DHS complex reveals insights into the hypusination mechanism.

Structure

July 2024

Architecture et Réactivité de l'ARN, CNRS UPR 9002, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Strasbourg, France. Electronic address:

The translation factor IF5A is highly conserved in Eukarya and Archaea and undergoes a unique post-translational hypusine modification by the deoxyhypusine synthase (DHS) enzyme. DHS transfers the butylamine moiety from spermidine to IF5A using NAD as a cofactor, forming a deoxyhypusine intermediate. IF5A is a key player in protein synthesis, preventing ribosome stalling in proline-rich sequences during translation elongation and facilitating translation elongation and termination.

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Epilepsy remains a major health concern as anti-seizure medications frequently fail, and there is currently no treatment to stop or prevent epileptogenesis, the process underlying the onset and progression of epilepsy. The identification of the pathological processes underlying epileptogenesis is instrumental to the development of drugs that may prevent the generation of seizures or control pharmaco-resistant seizures, which affect about 30% of patients. mTOR signalling and neuroinflammation have been recognized as critical pathways that are activated in brain cells in epilepsy.

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Article Synopsis
  • - The study investigates whether pathologic complete response (pCR) and major pathologic response (MPR) can reliably predict event-free survival (EFS) and overall survival (OS) in neoadjuvant trials for non-small cell lung cancer (NSCLC).
  • - A total of seven clinical trials involving 2385 patients were analyzed, demonstrating a strong correlation between pCR/MPR and 2-year EFS, but weaker associations with OS.
  • - The conclusion suggests that while pCR and MPR are good indicators of EFS, their predictive value for OS is less clear; further research is needed for more accurate data and understanding of patient outcomes.
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Background: Most neurological diseases have no curative treatment; therefore, focusing on prevention is key. Continuous research to uncover the protective and risk factors associated with different neurological diseases is crucial to successfully inform prevention strategies. eHealth has been showing promising advantages in healthcare and public health and may therefore be relevant to facilitate epidemiological studies.

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Colchicine and Risk of Venous Thromboembolism: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Can J Cardiol

July 2024

Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

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User-experience testing of an evidence-to-decision framework for selecting essential medicines.

PLOS Glob Public Health

January 2024

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.

Essential medicine lists (EMLs) are important medicine prioritization tools used by the World Health Organization (WHO) EML and over 130 countries. The criteria used by WHO's Expert Committee on the Selection and Use of Essential Medicines has parallels to the GRADE Evidence-to-Decision (EtD) frameworks. In this study, we explored the EtD frameworks and a visual abstract as adjunctive tools to strengthen the integrate evidence and improve the transparency of decisions of EML applications.

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Article Synopsis
  • Acute brain injuries, like traumatic brain injuries and strokes, are major causes of death and long-term disabilities around the world.
  • These injuries have different starting causes but share similar problems afterward that affect healing and recovery.
  • A recent course taught doctors new ways to help brain injury patients by using special monitoring and treatments to improve blood flow to the brain and understand recovery possibilities better.
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Polyphenols have gained increasing attention for their therapeutic potential, particularly in conditions like cancer, due to their established antioxidant and anti-inflammatory properties. Recent research highlights their ability to bind to transition metals, such as copper. This is particularly noteworthy given the key role of copper both in the initiation and progression of cancer.

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Central nervous system (CNS) glia, including astrocytes, microglia, and oligodendrocytes, play prominent roles in traumatic injury and degenerative disorders. Due to their importance, active pharmaceutical ingredients (APIs) are being developed to modulate CNS glia in order to improve outcomes in traumatic injury and disease. While many of these APIs show promise the majority of APIs that are systemically delivered show little penetration through the blood-brain barrier (BBB) or blood-spinal cord barrier (BSCB) and into the CNS, rendering them ineffective.

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Integrated procedures for accelerating, deepening, and leading genetic inquiry: A first application on human muscle secretome.

Mol Genet Metab

November 2023

Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" Chieti - Pescara, Chieti, Italy; Interuniversity Institute of Myology (IIM), Perugia, Italy. Electronic address:

Purpose: Beyond classical procedures, bioinformatic-assisted approaches and computational biology offer unprecedented opportunities for scholars. However, these amazing possibilities still need epistemological criticism, as well as standardized procedures. Especially those topics with a huge body of data may benefit from data science (DS)-assisted methods.

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Structural basis of dimerization of chemokine receptors CCR5 and CXCR4.

Nat Commun

October 2023

Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Euler Institute, Via G. Buffi 13, CH-6900, Lugano, Switzerland.

G protein-coupled receptors (GPCRs) are prominent drug targets responsible for extracellular-to-intracellular signal transduction. GPCRs can form functional dimers that have been poorly characterized so far. Here, we show the dimerization mechanism of the chemokine receptors CCR5 and CXCR4 by means of an advanced free-energy technique named coarse-grained metadynamics.

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Intellectual Disability and Behavioral Deficits Linked to CYFIP1 Missense Variants Disrupting Actin Polymerization.

Biol Psychiatry

January 2024

Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy. Electronic address:

Background: 15q11.2 deletions and duplications have been linked to autism spectrum disorder, schizophrenia, and intellectual disability. Recent evidence suggests that dysfunctional CYFIP1 (cytoplasmic FMR1 interacting protein 1) contributes to the clinical phenotypes observed in individuals with 15q11.

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Article Synopsis
  • Heliconius butterflies are a well-studied example of adaptive radiation, showcasing various specialized traits, but there's a lack of genomic data for many lineages.
  • The research presents comprehensive genome assemblies for 63 species in the Heliconiini tribe, including new and improved data for nine specific lineages.
  • This extensive dataset enables detailed phylogenetic analysis, examination of gene flow, and discovery of genetic innovations, enhancing our understanding of genome evolution and its implications for adaptive traits in these butterflies.
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The rapid spread of the SARS-CoV-2 virus has forced healthcare organizations to change their organization, introducing new ways of working, relating, communicating, and managing to cope with the growing number of hospitalized patients. Starting from the analysis of the narratives of healthcare workers who served in the intensive care units of 10 hospitals in Central and Northern Italy, this contribution intends to highlight elements present during the pandemic period within the investigated structures, which are considered factors that can influence the birth of organizational learning. Specifically, the data collected through interviews and focus groups were analyzed using the framework analysis method of Ritchie and Spencer.

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Article Synopsis
  • Microglial activation is crucial in diseases that involve neuroinflammation and neurodegeneration, with PET scans using TSPO to detect inflammation in the brain, although interpreting these results can be tricky.* -
  • The study finds that while TSPO expression increases in activated microglia in mouse models, it doesn't change in human diseases, indicating a difference in how TSPO is regulated across species.* -
  • Genetic differences in TSPO expression linked to the transcription factor AP1 are noted, suggesting that human TSPO-PET signals are more about the presence of inflammatory cells rather than their activation state.*
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Assessing the physicochemical stability and intracellular trafficking of mRNA-based COVID-19 vaccines.

Int J Pharm

September 2023

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via F. Marzolo, 5, Padova, Italy. Electronic address:

The emergence of SARS-CoV-2 in Wuhan, China in 2019 has had a profound impact on humanity in every facet. While vaccines against this viral pathogen have been approved a year later, limitations to this therapeutic intervention persist, such as drug sensitivity to transportation and storage conditions, as well as significant financial losses from non-injected resuspended vials. Our research delves into the effects of thermal denaturation (4 - 40 °C) and light irradiation (720 and 10460 kJ/m) on the mRNA-based vaccines BNT162b2 from BioNTech/Pfizer and mRNA-1273 from Moderna.

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