Discriminative stimulus properties of α-ethyltryptamine (α-ET) in rats: α-ET-like effects of MDMA, MDA and aryl-monomethoxy substituted derivatives of α-ET.

Rationale α-ET (α-ethyltryptamine), a homolog of the classical hallucinogen α-methyltryptamine, was once prescribed clinically as an antidepressant. Classical psychedelic drugs are currently of interest as potential pharmacotherapy for psychiatric disorders. Objectives Drug discrimination was used to (a) determine if α-ET-like stimulus effects could be engendered by the prototypical phenylalkylamines MDMA ("Ecstasy") or MDA ("Love Drug") and (b) evaluate the α-ET-like stimulus effects of four synthesized aryl-substituted monomethoxy analogs of α-ET (4-OMe-, 5-OMe-, 6-OMe- and 7-OMe-α-ET).

Combine Surgery and In Vitro Fertilization (IVF) in Endometriosis-Related Infertility: When and Why.

Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the presence of endometrial tissue outside the uterus, causing pelvic pain and infertility. Infertility arises mainly due to inflammatory mediators in the peritoneal fluid, contributing to local hypoestrogenism, which appears to exacerbate chronic inflammation and sensitize pelvic nerves. Local hypoestrogenism within endometriotic lesions contrasts with the systemic estrogen-dependent nature of the disease.

SIGMAP: an explainable artificial intelligence tool for SIGMA-1 receptor affinity prediction.

Developing sigma-1 receptor (S1R) modulators is considered a valuable therapeutic strategy to counteract neurodegeneration, cancer progression, and viral infections, including COVID-19. In this context, tools capable of accurately predicting S1R affinity are highly desirable. Herein, we present a panel of 25 classifiers trained on a curated dataset of high-quality bioactivity data of small molecules, experimentally tested as potential S1R modulators.

Spectral CT for non-invasive evaluation of bladder cancer grade.

Objective: To investigate the potential role of dual-energy spectral computer tomography (CT) quantitative parameters in the definition of bladder cancer (BCa) pathological grading.

Methods: This retrospective study evaluated the use of spectral CT imaging features for BCa. From 2021 to 2023, 63 patients with histologically-confirmed BCa diagnosis were examined at our Institution.

First-In-Class Thiosemicarbazone Metal Complexes Targeting the Sigma-2 Receptor (S2R) as an Innovative Strategy against Pancreatic Cancer.

Pancreatic cancer, with its increasing incidence and lowest 5-year survival rate, is predicted to become the second leading cause of cancer deaths by 2030. Current clinical trials have shown limited improvement, highlighting the need for new therapies. The sigma-2 receptor (S2R), with roles in tumor progression, is a target for novel thiosemicarbazones (TSCs).

Adenomyosis and Adolescence: A Challenging Diagnosis and Complex Management.

Adenomyosis is a chronic, hormone-related disease characterized by the presence of the endometrial glands and stroma within the myometrium. This condition can manifest in various features, focal or diffuse adenomyosis or as an adenomyoma, and it may involve different uterine walls (posterior, anterior, and/or lateral walls). The disease can also be classified into different degrees, as mild, moderate and severe, which can be associated with more intense symptoms, although this correlation is not always directly proportional.

Predicting faller status in persons with multiple sclerosis using the Multiple Sclerosis Walking Scale-12.

Background: Persons with multiple sclerosis (PwMS) are at an increased risk for falling, making it necessary to identify useful screening tools. The aims of this study were to 1) determine a cut-off score for the 12-item Multiple Sclerosis Walking Scale (MSWS-12) for identifying PwMS as fallers and 2) evaluate its predictive ability of faller status after controlling for other potential contributing factors.

Methods: Participant characteristics, MSWS-12, and falls in the last six months were collected on PwMS (n = 171) during a single session.

-Adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as Fluorescent Probes to Detect Microglia Activation through the Imaging of Cannabinoid Receptor Subtype 2 (CB2R).

Cannabinoid receptor subtype 2 (CB2R) is emerging as a pivotal biomarker to identify the first steps of inflammation-based diseases such as cancer and neurodegeneration. There is an urgent need to find specific probes that may result in green and safe alternatives to the commonly used radiative technologies, to deepen the knowledge of the CB2R pathways impacting the onset of the above-mentioned pathologies. Therefore, based on one of the CB2R pharmacophores, we developed a class of fluorescent -adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives spanning from the green to the near-infrared (NIR) regions of the light spectrum.

Experimental and computational study on morin and its complexes with Mg, Mn, Zn, and Al: Coordination and antioxidant properties.

Morin (MRN), an intriguing bioflavonol, has received increasing interest for its antioxidant properties, as have its metal complexes (M-MRN). Understanding their antioxidant behavior is critical to assess their pharmaceutical, nutraceutical potential, and therapeutic impact in the design of advanced antioxidant drugs. To this end, knowing the speciation of different H-MRN and M-MRN is pivotal to understand and compare their antioxidant ability.

Deep Infiltrating Endometriosis in Adolescence: Early Diagnosis and Possible Prevention of Disease Progression.

Endometriosis has a prevalence of 10% worldwide in premenopausal women. Probably, endometriosis begins early in the life of young girls, and it is commonly diagnosed later in life. The prevalence of deep infiltrating endometriosis (DIE) in adolescence is currently unknown due to diagnostic limits and underestimation of clinical symptoms.

AMALPHI: A Machine Learning Platform for Predicting Drug-Induced PhospholIpidosis.

Drug-induced phospholipidosis (PLD) involves the accumulation of phospholipids in cells of multiple tissues, particularly within lysosomes, and it is associated with prolonged exposure to druglike compounds, predominantly cationic amphiphilic drugs (CADs). PLD affects a significant portion of drugs currently in development and has recently been proven to be responsible for confounding antiviral data during drug repurposing for SARS-CoV-2. In these scenarios, it has become crucial to identify potential safe drug candidates in advance and distinguish them from those that may lead to false in vitro antiviral activity.

Synthesis and Biological Evaluation of Enantiomerically Pure () and ()[18F]OF-NB1 for Imaging the GluN2B Subunit-Containing NMDA Receptors.

GluN2B subunit-containing methyl-d-aspartate (NMDA) receptors have been implicated in various neurological disorders. Nonetheless, a validated fluorine-18 labeled positron emission tomography (PET) ligand for GluN2B imaging in the living human brain is currently lacking. The aim of this study was to develop a novel synthetic approach that allows an enantiomerically pure radiosynthesis of the previously reported PET radioligands ()[F]OF-NB1 and ()[F]OF-NB1 as well as to assess their and performance characteristics for imaging the GluN2B subunit-containing NMDA receptor in rodents.

The Intriguing Sigma-1 and Sigma-2 Receptors and Their Potential Therapeutic Roles 2.0.

For some time now, the research on sigma receptors has been at a high level of maturity but, despite everything that has already been achieved, further work in this field still holds huge appeal, with vast possibilities for original discoveries [...

Cytotoxic pathways activated by multifunctional thiosemicarbazones targeting sigma-2 receptors in breast and lung carcinoma cells.

Background: Multifunctional thiosemicarbazones (TSCs) able to bind sigma receptors and chelate metals are considered as a promising avenue for the treatment of pancreatic cancer due to the encouraging results obtained on in vitro and in vivo models. Here, we assessed the biochemical mechanism of these TSCs also on lung (A549) and breast (MCF7) cancer cells.

Methods: The density of sigma-2 receptors in normal (BEAS-2B and MCF10A) and in lung and breast (A549 and MCF7) cancer cells was evaluated by flow cytometry.

Screen-Printed Carbon Electrodes with Cationic Cyclodextrin Carbon Nanotubes and Ferrocenyl-Carnosine for Electrochemical Sensing of Hg(II).

The study reports the use of nanoassembly based on cationic cyclodextrin carbon nanotubes (CNT-CDs) and ferrocenylcarnosine (FcCAR) for electrochemical sensing of Hg(II) in aqueous solution. β-cyclodextrins (CDs) were grafted onto CNTs by a click chemistry reaction between heptakis-(6-azido-6-deoxy)-β-cyclodextrin and alkyne-terminated CNTs. The cationic amine groups on the CD units were produced by the subsequent reduction of the residual nitrogen groups.

Effect of Sodium Hydroxide and Tripolyphosphate on Curcumin Release from Chitosan-Based Macroparticles.

This work deals with the synthesis of bare and curcumin (CUR)-loaded chitosan (CS)-based macroparticles by ionic gelation using sodium hydroxide (NaOH) or sodium tripolyphosphate (TPP). The resulting spherical-shaped macroparticles were studied using various characterization techniques, Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC). The release of CUR from the CS-based particles with respect to time was analyzed, and the encapsulation efficiency and degree of swelling were studied.

Sigma-2 Receptor Ligand Binding Modulates Association between TSPO and TMEM97.

Sigma-2 receptor (S2R) is a S2R ligand-binding site historically associated with reportedly 21.5 kDa proteins that have been linked to several diseases, such as cancer, Alzheimer's disease, and schizophrenia. The S2R is highly expressed in various tumors, where it correlates with the proliferative status of the malignant cells.

Structure-Activity Relationships and Therapeutic Potential of Purinergic P2X7 Receptor Antagonists.

The purinergic P2X7 receptor (P2X7R), an ATP-gated non-selective cation channel, has emerged as a gatekeeper of inflammation that controls the release of proinflammatory cytokines. As a key player in initiating the inflammatory signaling cascade, the P2X7 receptor is currently under intense scrutiny as a target for the treatment of different pathologies, including chronic inflammatory disorders (rheumatoid arthritis and osteoarthritis), chronic neuropathic pain, mood disorders (depression and anxiety), neurodegenerative diseases, ischemia, cancer (leukemia), and many others. For these reasons, pharmaceutical companies have invested in discovering compounds able to modulate the P2X7R and filed many patent applications.

Development of Fluorescent 4-[4-(3-Spiro[isobenzofuran-1,4'-piperidin]-1'-yl)butyl]indolyl Derivatives as High-Affinity Probes to Enable the Study of σ Receptors via Fluorescence-Based Techniques.

Sigma (σ) receptor subtypes, σ and σ, are targets of wide pharmaceutical interest. The σ receptor holds promise for the development of diagnostics and therapeutics against cancer and Alzheimer's disease. Nevertheless, little is known about the mechanisms activated by the σ receptor.

Thermodynamic and voltammetric study on carnosine and ferrocenyl-carnosine.

A potentiometric study on the interactions of L-carnosine (CAR) (2-[(3-aminopropanoyl)amino]-3-(1-imidazol-5-yl)propanoic acid) with two toxic metal cations, Hg and Cd, is reported here. The elucidation of the metal (M)-CAR interactions in aqueous solution highlighted the speciation model for each system, the dependence of the formation constants of the complex species on ionic strength (0.15 ≤ /mol L ≤ 1) and temperature (288.

From speciation study to removal of Pb from natural waters by a carnosine-based polyacrylamide/azlactone copolymer.

A deep speciation study on L-carnosine (CAR) and Pb system was performed in aqueous solution with the aim to assess its potential use as a sequestering agent of metal cation. To determine the best conditions for Pb complexation, potentiometric measurements were carried out over a wide range of ionic strength (0.15 ≤ I/≤ 1 mol/L) and temperature (15 ≤ T/°C ≤ 37), and thermodynamic interaction parameters (logβ, ΔH, ΔG and TΔS) were determined.

Synthesis and Biological Evaluation of Enantiomerically Pure ()- and ()-[F]OF-NB1 for Imaging the GluN2B Subunit-Containing NMDA receptors.

GluN2B subunit-containing -methyl-d-aspartate (NMDA) receptors have been implicated in various neurological disorders. Nonetheless, a validated fluorine-18 labeled positron emission tomography (PET) ligand for GluN2B imaging in the living human brain is currently lacking. As part of our PET ligand development program, we have recently reported on the preclinical evaluation of [F]OF-NB1 - a GluN2B PET ligand with promising attributes for potential clinical translation.

N-adamantyl-anthranil amide derivatives: New selective ligands for the cannabinoid receptor subtype 2 (CB2R).

Cannabinoid type 2 receptor (CB2R) is a G-protein-coupled receptor that, together with Cannabinoid type 1 receptor (CB1R), endogenous cannabinoids and enzymes responsible for their synthesis and degradation, forms the EndoCannabinoid System (ECS). In the last decade, several studies have shown that CB2R is overexpressed in activated central nervous system (CNS) microglia cells, in disorders based on an inflammatory state, such as neurodegenerative diseases, neuropathic pain, and cancer. For this reason, the anti-inflammatory and immune-modulatory potentials of CB2R ligands are emerging as a novel therapeutic approach.