Dos(e)Age: Role of Dose and Age in the Long-Term Effect of Cannabinoids on Cognition

Cannabis is still the most widely used illicit drug around the world. While its use has always been prevalent among adolescents, recent evidence suggests that its consumption is also increasing among other population groups, such as pregnant women and aged people. Given the known impact of cannabis on brain development and behavior, it is important to dissect the possible long-term impact of its use across different age groups, especially on measures of cognitive performance. Animal models of cannabinoid exposure have represented a fundamental tool to characterize the long-lasting consequences of cannabinoids on cognitive performance and helped to identify possible factors that could modulate cannabinoids effects in the long term, such as the age of exposure and doses administered. This scoping review was systematically conducted using PubMed and includes papers published from 2015 to December 2021 that examined the effects of cannabinoids, either natural or synthetic, on cognitive performance in animal models where exposure occurred in the prenatal period, during adolescence, or in older animals. Overall, available data clearly point to a crucial role of age in determining the long-term effect of cannabinoid on cognition, highlighting possible detrimental consequences during brain development (prenatal and adolescent exposure) and beneficial outcomes in old age. In contrast, despite the recent advances in the field, it appears difficult to clearly establish a possible role of dosage in the effects of cannabinoids on cognition, especially when the adolescent period is taken into account.     

Differences in Salivary Proteins as a Function of PROP Taster Status and Gender in Normal Weight and Obese Subjects

Taste plays an important role in processes such as food choices, nutrition status and health. Salivary proteins contribute to taste sensitivity. Taste reduction has been associated with obesity. Gender influences the obesity predisposition and the genetic ability to perceive the bitterness of 6-n-propylthiouracil (PROP), oral marker for food preferences and consumption. We investigated variations in the profile of salivary proteome, analyzed by HPLC-ESI-MS, between sixty-one normal weight subjects (NW) and fifty-seven subjects with obesity (OB), based on gender and PROP sensitivity. Results showed variations of taste-related salivary proteins between NW and OB, which were differently associated with gender and PROP sensitivity. High levels of Ps-1, II-2 and IB-1 proteins belonging to basic proline rich proteins (bPRPs) and PRP-1 protein belonging to acid proline rich proteins (aPRPs) were found in OB males, who showed a lower body mass index (BMI) than OB females. High levels of Ps-1 protein and Cystatin SN (Cyst SN) were found in OB non-tasters, who had lower BMI than OB super-tasters. These new insights on the role of salivary proteins as a factor driving the specific weight gain of OB females and super-tasters, suggest the use of specific proteins as a strategic tool modifying taste responses related to eating behavior.     

Participation of the nucleobases in the regioselective backbone fragmentation of nucleic acids. A molecular dynamics and tandem mass spectrometric investigation on a model dinucleoside phosphotriester

The anions (I–III) obtained from O-methyl 5′-O-(5′-deoxythymidine) 3′-O-(2′,3′-dideoxyuridine) phosphate by the competitive removal of the 3-N-H protons of the nucleobases and of the methyl group from the phosphotriester bond, assume in the gas phase stable conformations as a function of their charge site. The mass-analyzed ion kinetic energy (MIKE) spectra of I and III show that the regioselective backbone cleavage of the internucleotidic linkage is controlled by the 2′-H proton transfer to the nucleobase within the 5′-end nucleoside. Similar pathways are taken by species II when the nucleobase is eliminated as neutral from the 5′-end nucleoside.     

A Review on Coordination Properties of Al(III) and Fe(III) toward Natural Antioxidant Molecules: Experimental and Theoretical Insights

This review focuses on the ability of some natural antioxidant molecules (i.e., hydroxycinnamic acids, coumarin-3-carboxylic acid, quercetin, luteolin and curcumin) to form Al(III)- and Fe(III)-complexes with the aim of evaluating the coordination properties from a combined experimental and theoretical point of view. Despite the contributions of previous studies on the chemical properties and biological activity of these metal complexes involving such natural antioxidants, further detailed relationships between the structure and properties are still required. In this context, the investigation on the coordination properties of Al(III) and Fe(III) toward these natural antioxidant molecules might deserve high interest to design water soluble molecule-based metal carriers that can improve the metal’s intake and/or its removal in living organisms.     

Structural Properties Governing Retention Mechanisms on Immobilized Artificial Membrane (IAM) HPLC Columns

The aims of this study were to investigate whether three commercially available immobilized artificial membrane (IAM) HPLC columns yield collinear data for neutral compounds, and whether IAM scales are distinct from the log P_oct (partition coefficient in the octanol/H₂O system) scale. With these objectives, the retention mechanisms on the IAM HPLC columns were analysed by linear solvation free‐energy relationships (LSERs). A set of 68 neutral model compounds with known solvatochromic parameters and log P_oct values was investigated, allowing a regular and broad exploration of property space. The resulting solvatochromic equations clearly indicate that the three IAM stationary phases retain small neutral solutes by a balance of intermolecular forces closely resembling those underlying partitioning in octanol/H₂O and retention on a reversed‐phase LC‐ABZ HPLC column. For all systems, the solute's size and hydrogen‐bond‐acceptor basicity are the two predominant factors, whereas dipolarity/polarisability and hydrogen‐bond‐donor acidity play only minor roles.     

Allylation of exocyclic N-Acyliminium ions generated from chiral N-[1-(phenylsulfonyl)alkyl]oxazolidin-2-ones

N-[1-(Phenylsulfonyl)alkyl]oxazolidin-2-ones are successfully prepared by condensation of the corresponding optically active oxazolidin-2-ones with aldehydes and benzenesulfinic acid. At low temperature, in the presence of titanium tetrachloride, these sulfones are converted into N-acyliminium ions, which react with allyltrimethylsilane with a variable degree of stereoselectivity. The best results are obtained with (R)-5,5-dimethyl-4-phenyloxazolidin-2-one as a chiral auxiliary. Cleavage of the oxazolidin-2-one ring with lithium/ammonia affords the corresponding homoallylamines, which reveal an absolute configuration opposite that expected on the basis of the usual steric effects. A complexation of the Lewis acid with the N-acyliminium ion may be responsible of this rather unusual stereochemical outcome.     

An unusual dimer of camptothecin-7-aldehyde

An intermolecular aldol reaction of 20S-camptothecin-7-aldehyde in the presence of strong bases affords an unusual dimeric compound, the structure and stereochemistry of which was assigned on the basis of NMR analysis and MM2 calculations.     

Azobioisosteres of Curcumin with Pronounced Activity against Amyloid Aggregation,Intracellular Oxidative Stress,and Neuroinflammation

Many (poly-)phenolic natural products, for example, curcumin and taxifolin, have been studied for their activity against specific hallmarks of neurodegeneration, such as amyloid-β 42 (Aβ42) aggregation and neuroinflammation. Due to their drawbacks, arising from poor pharmacokinetics, rapid metabolism, and even instability in aqueous medium, the biological activity of azobenzene compounds carrying a pharmacophoric catechol group, which have been designed as bioisoteres of curcumin has been examined. Molecular simulations reveal the ability of these compounds to form a hydrophobic cluster with Aβ42, which adopts different folds, affecting the propensity to populate fibril-like conformations. Furthermore, the curcumin bioisosteres exceeded the parent compound in activity against Aβ42 aggregation inhibition, glutamate-induced intracellular oxidative stress in HT22 cells, and neuroinflammation in microglial BV-2 cells. The most active compound prevented apoptosis of HT22 cells at a concentration of 2.5 μm (83 % cell survival), whereas curcumin only showed very low protection at 10 μm (21 % cell survival).