Discovery and Optimization of Indoline-Based Compounds as Dual 5-LOX/sEH Inhibitors: In Vitro and In Vivo Anti-Inflammatory Characterization
Abstract The design of multitarget drugs represents a promising strategy in medicinal chemistry and seems particularly suitable for the discovery of anti-inflammatory drugs. Here, we describe the identification of an indoline-based compound inhibiting both 5-lipoxygenase (5-LOX) and soluble epoxide hydrolase [...]
Extensive Molecular Dynamics Simulations Disclosed the Stability of mPGES-1 Enzyme and the Structural Role of Glutathione (GSH) Cofactor
Abstract A deep in silico investigation of various microsomal prostaglandin E2 synthase-1 (mPGES-1) protein systems is here reported using molecular dynamics (MD) simulations. Firstly, eight different proteins models (Models A−H) were built, starting from the active enzyme trimer system (Model A), [...]
Identification of 2,4-Dinitro-Biphenyl-Based Compounds as MAPEG Inhibitors
Abstract Multipronged strategy: 2,4-Dinitro-biphenyl-based compounds were identified as inhibitors of leukotriene C4 synthase (LTC4S) and 5-lipoxygenase-activating protein (FLAP), both members of the “Membrane Associated Proteins in Eicosanoid and Glutathione metabolism” (MAPEG) family involved in the biosynthesis of pro-inflammatory eicosanoids. The results [...]
Rational design of the zonulin inhibitor AT1001 derivatives as potential anti SARS-CoV-2
Abstract Although vaccines are greatly mitigating the worldwide pandemic diffusion of SARS-Cov-2, therapeutics should provide many distinct advantages as complementary approach to control the viral spreading. Here, we report the development of new tripeptide derivatives of AT1001 against SARS-CoV-2 Mpro. [...]
Indocyanine Green Endoscopy for Pituitary Adenomas with Parasellar Extension: Results from a Preliminary Case Series
Abstract Background Advances in visualization tools have brought new confidence, including endoscope-integrated indocyanine (E-ICG), which makes pituitary and skull-base surgery safer and more effective. We report here our preliminary experience with the use of E-ICG to 1) visualize the cavernous segment of [...]
“Sagittal Crest”: Definition, Stepwise Dissection, and Clinical Implications From a Transorbital Perspective
Abstract BACKGROUND: The recent development of the superior eyelid endoscopic transorbital approach (SETOA) offered a new route for the management of cavernous sinus and middle cranial fossa tumors. As a result, a constant anatomic landmark of the surgical pathway after drilling the medial edge of the greater sphenoid wing (GSW) [...]
Zonulin Antagonist, Larazotide (AT1001), As an Adjuvant Treatment for Multisystem Inflammatory Syndrome in Children: A Case Series
Abstract OBJECTIVES: A recent study suggests that Multisystem Inflammatory Syndrome in Children (MIS-C) is triggered by gastrointestinal breach of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral particles from the gut lumen into systemic circulation. The virus remains in the [...]
Optimization of Peripheral Blood Mononuclear Cell Extraction from Small Volume of Blood Samples: Potential Implications for Children-Related Diseases
Abstract Managing medical procedures for children with problematic disorders is a challenging approach, especially in the case of blood withdrawal for autism spectrum disorder-affected children. Peripheral blood mononuclear cells (PBMC) represent an important cellular model to study immune responses and [...]
Identification of a dual acting SARS-CoV-2 proteases inhibitor through in silico design and step-by-step biological characterization
Abstract COVID-19 pandemic, starting from the latest 2019, and caused by SARS-CoV-2 pathogen, led to the hardest health-socio-economic disaster in the last century. Despite the tremendous scientific efforts, mainly focused on the development of vaccines, identification of potent and efficient [...]
Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation
Abstract A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the pathogen responsible for the outbreak of a severe, rapidly developing pneumonia (Coronavirus disease 2019, COVID-19). The virus enzyme, called 3CLpro or main protease (Mpro), [...]
Identification of 2-(thiophen-2-yl)acetic Acid-Based Lead Compound for mPGES-1 Inhibition
We report the implementation of our in silico/synthesis pipeline by targeting the glutathione-dependent enzyme mPGES-1, a valuable macromolecular target in both cancer therapy and inflammation therapy. Specifically, by using a virtual fragment screening approach of aromatic bromides, straightforwardly modifiable by the [...]
Artificial Intelligence: the “Trait D’Union” in Different Analysis Approaches of Autism Spectrum Disorder Studies
Abstract Autistic Spectrum Disorder (ASD) is a neurodevelopmental condition affecting approximately 1 out of 70 (range 1:59 - 1:89) children worldwide. It is characterized by a delay in cognitive capabilities, repetitive and restricted behaviors and deficit in communication and social [...]
Humoral signatures of protective and pathological SARS-CoV-2 infection in children
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune [...]
Humoral signatures of protective and pathological SARS-CoV-2 infection in children
Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying [...]
In silico Analysis Revealed Potential Anti-SARS-CoV-2 Main Protease Activity by the Zonulin Inhibitor Larazotide Acetate
Abstract The most severe outcome of COVID-19 infection is the development of interstitial pneumonia causing acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS), both responsible for the infected patients' mortality. ALI and ARDS are characterized by a leakage [...]
