COVID19 infection and vaccination and the risk of pituitary apoplexy: an entangled yarn.

Purpose: Pituitary apoplexy (PA) has been increasingly reported in association with both infection from and vaccination for COVID19. Our aim was to analyse the available published cases and compare the clinical characteristics in the two groups (infection vs vaccination).

Methods: We systematically reviewed the published literature for all cases of PA associated with COVID19 infection or vaccination.

SARS-Cov-2 Infection: A New Risk Factor for Pituitary Apoplexy?

Background: Pituitary apoplexy (PA) can arise from haemorrhage or ischaemia of pituitary tissue and is characterized by abrupt onset of headache, visual impairment and hypopituitarism. COVID-19 may be associated with various degrees of vascular complications and, recently, its relationship with PA has been suggested. Cases Presentation Case 1: A 64-year-old male with type 2 diabetes, hypertension and coronary heart disease was admitted to the ER, after several days of asymptomatic COVID-19 infection, with symptoms of PA of a known non-functioning pituitary macroadenoma.

Conjugation to gold nanoparticles of methionine gamma-lyase, a cancer-starving enzyme. Physicochemical characterization of the nanocomplex for prospective nanomedicine applications.

The pyridoxal 5'-dependent enzyme methionine γ-lyase (MGL) catalyzes the degradation of methionine. This activity has been profitable to develop an antitumor agent exploiting the strict dependence of most malignant cells on the availability of methionine. Indeed, methionine depletion blocks tumor proliferation and leads to an increased susceptibility to anticancer drugs.

Older Adults with Type 2 Diabetes Treated with Metformin: AME-MET Study - A Multicentric Real-world Study in Italy.

Aims: Metformin is the most widely used drug for the first-line treatment of type 2 diabetes mellitus (T2DM), but its use and schedule have been poorly investigated in elderly patients.

Methods: We conducted an observational, cross-sectional, multicentric study on metformin in T2DM outpatients older than 65 years who were taking the drug for at least 6 months and referred to Italian Endocrinology and Diabetology Services. The primary endpoint was daily metformin dose, and secondary endpoints were the correlations between metformin dose and age, comorbidities, and concomitant use of other drugs.

Effectiveness, Safety, and Appropriateness in the Use of the Fixed-Ratio Combination of Insulin Glargine and Lixisenatide in Type 2 Diabetes: The ENSURE Retrospective Real-World Study.

Introduction: Pivotal trials documented glycemic benefits of fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide (iGlarLixi), with no weight gain and low hypoglycemia risk in type 2 diabetes (T2D). This study aimed at assessing effectiveness and patterns of use of iGlarLixi in a real-world setting.

Methods: This was a retrospective, multicenter, study, based on electronic medical records.

Heat and cold denaturation of yeast frataxin: The effect of pressure.

Yfh1 is a yeast protein with the peculiar characteristic to undergo, in the absence of salt, cold denaturation at temperatures above the water freezing point. This feature makes the protein particularly interesting for studies aiming at understanding the rules that determine protein fold stability. Here, we present the phase diagram of Yfh1 unfolding as a function of pressure (0.

A novel hotspot of gelsolin instability triggers an alternative mechanism of amyloid aggregation.

Gelsolin comprises six homologous domains, named G1 to G6. Single point substitutions in this protein are responsible for AGel amyloidosis, a hereditary disease causing progressive corneal lattice dystrophy, cutis laxa, and polyneuropathy. Although several different amyloidogenic variants of gelsolin have been identified, only the most common mutants present in the G2 domain have been thoroughly characterized, leading to clarification of the functional mechanism.

Structure-activity relationship around PI-2620 highlights the importance of the nitrogen atom position in the tricyclic core.

Tau aggregates represent a critical pathology in Alzheimer's disease (AD) and other forms of dementia. The extent of Tau neurofibrillary tangles across defined brain regions corresponds well to the observed level of cognitive decline in AD. Compound 1 (PI-2620) was recently identified as a promising Tau positron emission tomography tracer for AD and non-AD tauopathies.

Lead Optimization Highlights the Importance of Off-Target Assays to Develop a PET Tracer for the Detection of Pathological Aggregated Tau in Alzheimer's Disease and Other Tauopathies.

The first candidate was tested in healthy controls and subjects with Alzheimer's disease (AD). As displayed off-target binding to monoamine oxidase A (MAO-A), a new lead with improved binding to Tau and decreased MAO-A binding was required. For compound optimization, Tau binding assays based on both human AD brain homogenate and Tau-paired helical filaments were employed.

Use of Exogenous Enzymes in Human Therapy: Approved Drugs and Potential Applications.

The development of safe and efficacious enzyme-based human therapies has increased greatly in the last decades, thanks to remarkable advances in the understanding of the molecular mechanisms responsible for different diseases, and the characterization of the catalytic activity of relevant exogenous enzymes that may play a remedial effect in the treatment of such pathologies. Several enzyme-based biotherapeutics have been approved by FDA (the U.S.

Exploiting gold nanoparticles for diagnosis and cancer treatments.

Gold nanoparticles (AuNPs) represent a relatively simple nanosystem to be synthesised and functionalized. AuNPs offer numerous advantages over different nanomaterials, primarily due to highly optimized protocols for their production with sizes in the range 1-150 nm and shapes, spherical, nanorods (AuNRs), nanocages, nanostars or nanoshells (AuNSs), just to name a few. AuNPs possess unique properties both from the optical and chemical point of view.

Discovery of 2-(4-(2-fluoroethoxy)piperidin-1-yl)-9-methyl-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2014) as PET tracer for the detection of pathological aggregated tau in Alzheimer's disease and other tauopathies.

The compound screening was initiated with a direct staining assay to identify compounds binding to Tau aggregates and not Abeta plaques using human brain sections derived from late stage Alzheimer's disease donors. The binding of Tau aggregate selective compounds was then quantitatively assessed with human brain derived paired helical filaments utilizing the label-free Back Scattering Interferometry assay. In vivo biodistribution experiments of selected fluorine-18 labeled compounds were performed in mice to assess brain uptake, brain washout, and defluorination.

Interplay between extracellular polymeric substances (EPS) from a marine diatom and model nanoplastic through eco-corona formation.

The occurrence of nanoplastics in oceans' surface waters is no more a hypothesis and it could severely affect marine organisms from different trophic levels. Nanoscale particles interaction with dissolved natural organic matter (NOM) significantly influence their behaviour and consequently bioavailability and toxicity to marine species. Extracellular polymeric substances (EPS) are among the main components of the NOM pool in seawater yet have been so far little investigated for their effect in altering the physical-chemical properties of nanosized objects.

Discovery and preclinical characterization of [F]PI-2620, a next-generation tau PET tracer for the assessment of tau pathology in Alzheimer's disease and other tauopathies.

Purpose: Tau deposition is a key pathological feature of Alzheimer's disease (AD) and other neurodegenerative disorders. The spreading of tau neurofibrillary tangles across defined brain regions corresponds to the observed level of cognitive decline in AD. Positron-emission tomography (PET) has proved to be an important tool for the detection of amyloid-beta (Aβ) aggregates in the brain, and is currently being explored for detection of pathological misfolded tau in AD and other non-AD tauopathies.

Engineering methionine γ-lyase from Citrobacter freundii for anticancer activity.

Methionine deprivation of cancer cells, which are deficient in methionine biosynthesis, has been envisioned as a therapeutic strategy to reduce cancer cell viability. Methionine γ-lyase (MGL), an enzyme that degrades methionine, has been exploited to selectively remove the amino acid from cancer cell environment. In order to increase MGL catalytic activity, we performed sequence and structure conservation analysis of MGLs from various microorganisms.

Soluble and Nanoporous Silica Gel-Entrapped Methionine -Lyase.

Methionine γ-lyase is a pyridoxal 5'-phosphate dependent tetramer that catalyzes the α,γ-elimination of methionine in ammonia, methanethiol and α-ketobutyrate. MGL catalytic power has been exploited as a therapeutic strategy to reduce the viability of cancer cells or bacteria. In order to obtain a stable enzyme to be delivered at the site of action, MGL can be encapsulated in a variety of matrices.

TiO nanoparticles in seawater: Aggregation and interactions with the green alga Dunaliella tertiolecta.

Titanium dioxide nanoparticles (TiO NPs) have been widely employed in industrial applications, thus rising concern about their impact in the aquatic environment. In this study we investigated the chemical behaviour of TiO NPs in the culture medium and its effect on the green alga Dunaliella tertiolecta, in terms of growth inhibition, oxidative stress, ROS (Reactive Oxygen Species) accumulation and chlorophyll content. In addition, the influence of exopolymeric substances (EPS) excreted by the microalgae on the stability of NPs has been evaluated.

Gene cloning, characterization, and cytotoxic activity of methionine γ-lyase from Clostridium novyi.

The exploitation of methionine-depleting enzyme methionine γ-lyase (MGL) is a promising strategy against specific cancer cells that are strongly dependent on methionine. To identify MGL from different sources with high catalytic activity and efficient anticancer action, we have expressed and characterized MGL from Clostridium novyi and compared its catalytic efficiency with the previously studied MGL from Citrobacter freundii. The purified recombinant MGL exhibits k and k /K for methionine γ-elimination reaction that are 2.

Temperature and pressure effects on GFP mutants: explaining spectral changes by molecular dynamics simulations and TD-DFT calculations.

By combining spectroscopic measurements under high pressure with molecular dynamics simulations and quantum mechanics calculations we investigate how sub-angstrom structural perturbations are able to tune protein function. We monitored the variations in fluorescence output of two green fluorescent protein mutants (termed Mut2 and Mut2Y, the latter containing the key T203Y mutation) subjected to pressures up to 600 MPa, at various temperatures in the 280-320 K range. By performing 150 ns molecular dynamics simulations of the protein structures at various pressures, we evidenced subtle changes in conformation and dynamics around the light-absorbing chromophore.

Development and Pharmacological Characterization of Selective Blockers of 2-Arachidonoyl Glycerol Degradation with Efficacy in Rodent Models of Multiple Sclerosis and Pain.

We report the discovery of compound 4a, a potent β-lactam-based monoacylglycerol lipase (MGL) inhibitor characterized by an irreversible and stereoselective mechanism of action, high membrane permeability, high brain penetration evaluated using a human in vitro blood-brain barrier model, high selectivity in binding and affinity-based proteomic profiling assays, and low in vitro toxicity. Mode-of-action studies demonstrate that 4a, by blocking MGL, increases 2-arachidonoylglycerol and behaves as a cannabinoid (CB1/CB2) receptor indirect agonist. Administration of 4a in mice suffering from experimental autoimmune encephalitis ameliorates the severity of the clinical symptoms in a CB1/CB2-dependent manner.

A SELDI-TOF approach to ecotoxicology: comparative profiling of low molecular weight proteins from a marine diatom exposed to CdSe/ZnS quantum dots.

Quantum dots (QDs), namely semiconductor nanocrystals, due to their particular optical and electronic properties, have growing applications in device technology, biotechnology and biomedical fields. Nevertheless, the possible threat to human health and the environment have attracted increasing attention as the production and applications of QDs increases rapidly while standard evaluation of safety lags. In the present study we performed proteomic analyses, by means of 2D gel electrophoresis and Surface Enhanced Laser Desorption Ionization-Time of Flight-Mass Spectrometry (SELDI-TOF-MS).

The response of Phaeodactylum tricornutum to quantum dot exposure: Acclimation and changes in protein expression.

Nanotechnology has a great potential to improve life and environmental quality, however the fate of nanomaterials in the ecosystems, their bioavailability and potential toxicity on living organisms are still largely unknown, mainly in the marine environment. Genomics and proteomics are powerful tools for understanding molecular mechanisms triggered by nanoparticle exposure. In this work we investigated the effect of exposure to CdSe/ZnS quantum dots (QDs) in the marine diatom Phaeodactylum tricornutum, using different physiological, biochemical and molecular approaches.

Temperature and pressure effects on C112S azurin: volume, expansivity, and flexibility changes.

The pressure-induced unfolding of the mutant C112S azurin from Pseudomonas aeruginosa was monitored both under steady state and dynamic conditions. The unfolding profiles were obtained by recording the spectral shift of the fluorescence emission as well as by phosphorescence intensity measurements. We evaluated the difference in free energy, ΔG, as a function of pressure and temperature.

The gastric CB1 receptor modulates ghrelin production through the mTOR pathway to regulate food intake.

Over the years, the knowledge regarding the relevance of the cannabinoid system to the regulation of metabolism has grown steadily. A central interaction between the cannabinoid system and ghrelin has been suggested to regulate food intake. Although the stomach is the main source of ghrelin and CB1 receptor expression in the stomach has been described, little information is available regarding the possible interaction between the gastric cannabinoid and ghrelin systems in the integrated control of energy homeostasis.

A stereoselective approach to peptidomimetic BACE1 inhibitors.

Aiming at identifying new scaffolds to generate beta-secretase (BACE1) inhibitors we developed peptidomimetics based on a 1,4-benzodiazepine core (3a-d), their seco-analogs (4a-b), and linear analogs (5a-h), by stereoselective approaches. We herein discuss the synthesis, molecular modeling and in vitro studies for the newly developed ligands. Compounds 5c and 5h behaved as BACE1 inhibitors on the isolated enzyme and in cellular studies.