Melatonin Reduces Mito-Inflammation in Ischaemic Hippocampal HT22 Cells and Modulates the cGAS-STING Cytosolic DNA Sensing Pathway and FGF21 Release.

Mitochondrial dysfunction is a key event in many pathological conditions, including neurodegenerative processes. When mitochondria are damaged, they release damage-associated molecular patterns (DAMPs) that activate mito-inflammation. The present study assessed mito-inflammation after in vitro oxygen-glucose deprivation as a representation of ischaemia, followed by reoxygenation (OGD/R) of HT22 cells and modulation of the inflammatory response by melatonin.

Melatonin modulates the Notch1 signaling pathway and Sirt3 in the hippocampus of hypoxic-ischemic neonatal rats.

The Notch1 signaling pathway plays a crucial role in the development of the central nervous system, governing pivotal functional activities in the brain, such as neurogenesis. Sirt3 is instrumental in managing mitochondrial homeostasis and is essential to cell survival. Dysregulation of these signaling pathways is implicated in the pathogenesis of a wide range of diseases, including neurodegenerative disorders such as stroke.

Dendritic cell vaccines as cancer treatment: focus on 13 years of manufacturing and quality control experience in advanced therapy medicinal products.

Background Aims: Dendritic cells (DCs) are professional antigen-presenting cells of the mammalian immune system. Ex vivo differentiated DCs represent a unique Advanced Therapy Medicinal Product (ATMP), used in several clinical trials as personalized cancer immunotherapy. The therapy's reliability depends on its capacity to produce high-quality mature DCs (mDCs) in compliance with Good Manufacturing Practices.

In vitro CAR-T cell killing: validation of the potency assay.

For advanced therapy medicinal products, the development and validation of potency assays are required, in accordance with international guidelines, to characterise the product and obtain reliable and consistent data. Our purpose was to validate the killing assay for the evaluation of autologous anti-CD19 chimeric antigen receptor (CAR) T potency. We used CD4 + and CD8 + lymphocytes or anti-CD19 CAR-T cells as effector cells and REH (CD19 +) or MOLM-13 (CD19 -) cell lines as target cells.

Melatonin Modulates Cell Cycle Dynamics and Promotes Hippocampal Cell Proliferation After Ischemic Injury in Neonatal Rats.

Promoting neural cell proliferation may represent an important strategy for enhancing brain repair after developmental brain injury. The present study aimed to assess the effects of melatonin on cell proliferation after an ischemic injury in the developing hippocampus, focusing on cell cycle dynamics. After in vivo neonatal hypoxia-ischemia (HI), hippocampal cell cycle dynamics were assessed by flow cytometry, together with histological evaluation of dentate gyrus cellularity and proliferation.

Hypoxic ischemic brain injury: animal models reveal new mechanisms of melatonin-mediated neuroprotection.

Oxidative stress (OS) and inflammation play a key role in the development of hypoxic-ischemic (H-I) induced brain damage. Following H-I, rapid neuronal death occurs during the acute phase of inflammation, and activation of the oxidant-antioxidant system contributes to the brain damage by activated microglia. So far, in an animal model of perinatal H-I, it was showed that neuroprostanes are present in all brain damaged areas, including the cerebral cortex, hippocampus and striatum.

MiR-126 and miR-146a as Melatonin-Responsive Biomarkers for Neonatal Brain Ischemia.

Despite advances in obstetric and neonatal care, challenges remain in early identification of neonates with encephalopathy due to hypoxia-ischemia who are undergoing therapeutic hypothermia. Therefore, there is a deep search for biomarkers that can identify brain injury. The aims of this study were to investigate the serum and brain expressions of two potential biomarkers, miR-126/miR-146a, in a preclinical model of hypoxia-ischemia (HI)-induced brain injury, and to explore their modulation during melatonin treatment.

Melatonin in Newborn Infants Undergoing Surgery: A Pilot Study on Its Effects on Postoperative Oxidative Stress.

Surgery is frequently associated with excessive oxidative stress. Melatonin acts as an antioxidant and transient melatonin deficiency has been described in neonatal surgical patients. This randomized, blinded, prospective pilot study tested the hypothesis that oral melatonin supplementation in newborn infants undergoing surgery is effective in reducing perioperative oxidative stress.

The Endocannabinoid System as a Target for Neuroprotection/Neuroregeneration in Perinatal Hypoxic-Ischemic Brain Injury.

The endocannabinoid (EC) system is a complex cell-signaling system that participates in a vast number of biological processes since the prenatal period, including the development of the nervous system, brain plasticity, and circuit repair. This neuromodulatory system is also involved in the response to endogenous and environmental insults, being of special relevance in the prevention and/or treatment of vascular disorders, such as stroke and neuroprotection after neonatal brain injury. Perinatal hypoxia-ischemia leading to neonatal encephalopathy is a devastating condition with no therapeutic approach apart from moderate hypothermia, which is effective only in some cases.

Melatonin, tunneling nanotubes, mesenchymal cells, and tissue regeneration.

Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs. Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various lineages. However, when transplanted, they lose part of their multipotency and immunomodulatory properties, and most of them die after injection into the damaged tissue.

Stability Program in Dendritic Cell Vaccines: A "Real-World" Experience in the Immuno-Gene Therapy Factory of Romagna Cancer Center.

Advanced therapy medical products (ATMPs) are rapidly growing as innovative medicines for the treatment of several diseases. Hence, the role of quality analytical tests to ensure consistent product safety and quality has become highly relevant. Several clinical trials involving dendritic cell (DC)-based vaccines for cancer treatment are ongoing at our institute.

Human-rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic-ischemic pathway melatonin-sensitive.

Neonatal encephalopathy (NE) is a pathological condition affecting long-term neurodevelopmental outcomes. Hypothermia is the only therapeutic option, but does not always improve outcomes; hence, researchers continue to hunt for pharmaceutical compounds. Melatonin treatment has benefitted neonates with hypoxic-ischemic (HI) brain injury.

Automated-Mechanical Procedure Compared to Gentle Enzymatic Tissue Dissociation in Cell Function Studies.

The first step to obtain a cellular suspension from tissues is the disaggregation procedure. The cell suspension method has to provide a representative sample of the different cellular subpopulations and to maximize the number of viable functional cells. Here, we analyzed specific cell functions in cell suspensions from several rat tissues obtained by two different methods, automated-mechanical and enzymatic disaggregation.

Tunneling nanotubes and mesenchymal stem cells: New insights into the role of melatonin in neuronal recovery.

Efficient cell-to-cell communication is essential for tissue development, homeostasis, and the maintenance of cellular functions after injury. Tunneling nanotubes (TNTs) have emerged as a new important method of cell-to-cell communication. TNTs are primarily established between stressed and unstressed cells and can transport a variety of cellular components.

MicroRNA-16 Restores Sensitivity to Tyrosine Kinase Inhibitors and Outperforms MEK Inhibitors in -Mutated Non-Small Cell Lung Cancer.

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Chemotherapy, the treatment of choice in non-operable cases, achieves a dismal success rate, raising the need for new therapeutic options. In about 25% of NSCLC, the activating mutations of the oncogene define a subclass that cannot benefit from tyrosine kinase inhibitors (TKIs).

Melatonin reshapes the mitochondrial network and promotes intercellular mitochondrial transfer via tunneling nanotubes after ischemic-like injury in hippocampal HT22 cells.

Mitochondrial dysfunction is considered one of the hallmarks of ischemia/reperfusion injury. Mitochondria are plastic organelles that undergo continuous biogenesis, fusion, and fission. They can be transferred between cells through tunneling nanotubes (TNTs), dynamic structures that allow the exchange of proteins, soluble molecules, and organelles.

Potency Assessment of Dendritic Cell Anticancer Vaccine: Validation of the Co-Flow DC Assay.

For many years, oncological clinical trials have taken advantage of dendritic cells (DC) for the design of DC-based cellular therapies. This has required the design of suitable quality control assays to evaluate the potency of these products. The purpose of our work was to develop and validate a novel bioassay that uses flow cytometry as a read-out measurement.

Detection and Investigation of Extracellular Vesicles in Serum and Urine Supernatant of Prostate Cancer Patients.

Prostate Cancer (PCa) is one of the most frequently identified urological cancers. PCa patients are often over-diagnosed due to still not highly specific diagnostic methods. The need for more accurate diagnostic tools to prevent overestimated diagnosis and unnecessary treatment of patients with non-malignant conditions is clear, and new markers and methods are strongly desirable.

The Synthetic Cannabinoid URB447 Reduces Brain Injury and the Associated White Matter Demyelination after Hypoxia-Ischemia in Neonatal Rats.

The number of functions controlled by the endocannabinoid system in health and disease continues growing over the years. In the brain, these include the modulation of harmful events such as glutamate excitotoxicity, oxidative stress, and inflammation, mainly regulated by activation/blockade of CB/CB cannabinoid receptors. In the present work, we evaluated the capacity of the CB antagonist/CB agonist synthetic cannabinoid URB447 on reducing neurodegeneration after brain injury.

Unexpected low expression of platelet fibrinogen receptor in patients with chronic myeloproliferative neoplasms: how does it change with aspirin?

This study was conducted to evaluate the expression of fibrinogen receptors on platelets of Philadelphia-negative chronic myeloproliferative neoplasm (MPN) patients. We collected blood samples from 40 consecutive MPN patients and healthy volunteers. We performed flow cytometry analysis of P-selectin expression and integrin beta-3, activation of glycoprotein (GP) IIb/IIIa and fibrinogen receptor exposure (PAC-1 binding).