Polycationic calixarene micellar aggregate as a novel iodophor platform for on-demand iodine release to bacteria.

Iodine is the most potent antiseptic agent used in clinical applications, but its volatility and toxicity are serious drawbacks that are stimulating the search of new strategies to achieve formulations stable at low iodine concentration. Here, we report that polycationic micellar aggregates, formed by the self-assembling of the amphiphilic choline-calix[4]arene derivative (CholCalix) in aqueous medium, are able to complex triiodide anions (I) both in solution and in solid phase. This novel iodophor enhances the stability of 0.

Rapid G4 Ligand Screening Through Spectral Changes Using HT-SRCD with Minimal Material.

The development of molecules that interact with G-quadruplex (G4) sequences requires effective evaluation methods. Several techniques are currently available, including nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and mass spectrometry (MS), fluorescence using FRET-melting, G4-fluorescent intercalator displacement assay (G4-FID) and affinity chromatography. Among these, CD spectroscopy is gaining prominence due to its lower material requirements, faster experimentation and quicker data processing.

Synergic Effect of Methyl-β-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic Solution.

Nepafenac is an anti-inflammatory drug used in ophthalmology, marketed as a suspension due to its low aqueous solubility. A solution formulation could provide better bioavailability than suspension and facilitate single unit doses, avoiding the use of preservatives which are required to maintain sterility in multidose packaging. In this study, solubilization of nepafenac was achieved in the presence of randomly methylated β-cyclodextrin (RAMEB) and the actual complexation was assessed by NMR and phase-solubility studies.

Extracts: A Preliminary Comparative Study on Phytochemical Profiles and Bioactive Properties of Valuable Fraction and By-Product.

L. () (Lamiaceae) is an aromatic Mediterranean plant widely used in food, cosmetics, and traditional medicine due to its aroma and rich content of bioactive compounds. While its leaves and flowers are commonly utilized, lignified stems are often discarded.

Carboxylic ester hydrolases from Antarctic psychrophilic Psychrobacter strains: From genome prospecting to biotreatment of polyester plastics.

Background: Antarctica can serve as the source of novel extremophilic microorganisms and biomolecules, including extremozymes which could find applications in bioremediation processes for the presence of enzymes able to degrade plastic polymers. Carboxylic ester hydrolases (EC 3.1.

Inclusion Complex of a Cationic Mono-Choline-β-Cyclodextrin Derivative with Resveratrol: Preparation, Characterization, and Wound-Healing Activity.

Resveratrol is one of the most extensively studied natural products due to its pleiotropic health benefits. However, its low water solubility and limited stability hinder its application in the nutraceutical, cosmetic, and pharmaceutical sectors. In this work, we investigated the ability of a cationic mono-choline-β-cyclodextrin derivative to complex -resveratrol.

Untargeted Diversity-Oriented Synthesis for the Discovery of New Antitumor Agents: An Integrated Approach of Inverse Virtual Screening, Bioinformatics, and Omics for Target Deconvolution.

Molecular diversity is one of the most pursued objectives in drug discovery, and diversity-oriented synthesis (DOS) perfectly responds to the achievement of this goal. In this paper, we describe a DOS approach applied to the antitumor field with the aim of identifying new anticancer structures and their associated targets. To accomplish this ambitious project, after an initial stage of phenotypic evaluation, we set up an integrated platform of inverse virtual screening (IVS), bioinformatics, and omics to predict the biological targets of the most promising compounds and .

Development of a γ-Cyclodextrin-Based Cryogel Loaded with Trimethoprim for Acne Treatment: Design, Synthesis, and In Vitro Evaluation.

Innovative functional materials integrating host-guest complexes in cryogels offer promising applications in topical drug delivery, enhancing drug solubility and stability. In this study, we designed and developed a cryogel-based patch for acne treatment by polymerizing an acrylate-functionalized γ-cyclodextrin (γ-CD) and trimethoprim (TMP) inclusion complex with [2-(acryloyloxy)ethyl]trimethylammonium chloride (AETMA) at low temperatures. A multistep workflow was applied to synthesize the inclusion complex via mortar-assisted kneading, followed by cryogel formulation through radical cryopolymerization.

An Overview of α-Pyrones as Phytotoxins Produced by Plant Pathogen Fungi.

Crop diseases negatively affect the quality and quantity of agricultural products, with significant economic and social consequences. These problems become emergencies in a world where the safe production of food for human health is becoming increasingly pressing. Microorganisms, including phytopathogenic fungi, are the main organisms responsible for these diseases, which cause devastating damage.

Fragments of cathelicidins PMAP-36 and BMAP-27 and their D-enantiomers: Effects of all D substitutions on structure, protease resistance and antimicrobial properties.

Antimicrobial peptides (AMPs) are natural molecules of great interest in the fight against bacteria and in addressing antibiotic resistance. Their use as antimicrobial drugs is still limited due to their cytotoxicity and poor resistance to proteolysis. PMAP-36 and BMAP-27 are cathelicidins that contribute to innate immunity.

Cannabidiol attenuates epileptic phenotype and increases survival in a mouse model of developmental and epileptic encephalopathy type 1.

Objective: Developmental and epileptic encephalopathy type 1 (DEE1) is a rare drug-resistant pediatric epilepsy caused by trinucleotide repeat expansions in the X-linked ARX gene, leading to elongation of the first polyalanine tract. It presents with early onset tonic seizures or spasms, developmental and cognition delay, and high risk of premature mortality. We evaluated the therapeutic potential of highly purified cannabidiol (CBD) in Arx mice, a genetic DEE1 model that replicates key features of the human condition.

The endocannabinoidome-gut microbiome-brain axis as a novel therapeutic target for autism spectrum disorder.

Introduction: Autism spectrum disorder (ASD) is characterized by disruption of the gut-brain axis, which leads to behavioral, psychiatric, metabolic and gastrointestinal symptoms. Effective ASD treatments are limited. Research highlights the roles of the endocannabinoidome (eCBome) and gut microbiome (GM), both crucial for brain and gut function.

Combined CB1 antagonist AM6545 and NOP agonist SCH221510 worsen DSS-induced colitis in mice.

Background: Despite the broad range of treatment options available for intestinal inflammation, the development of novel therapeutics remains essential due to the diminishing effectiveness of current therapies over time. Both the endocannabinoid system (ECS) and nociceptin/orphanin FQ peptide (NOP) receptors have been implicated in the pathogenesis of diseases associated with intestinal inflammation, highlighting their potential as therapeutic targets.

Objectives: We hypothesized that an interaction exists between cannabinoid receptors 1 and 2 (CB1 and CB2) and the NOP receptor, which may hold therapeutic relevance for the treatment of colitis.

Toward a Green SPPS: The Use of an Innovative Mesoporous pDVB Support for Environmentally Friendly Solvents.

This study explores the use of a novel polymeric mesoporous support (pDVB) for solid-phase peptide synthesis (SPPS), with the aim of improving the efficiency and sustainability of the process. The pDVB support, functionalized with the Fmoc-Rink amide linker, offers advantages over conventional supports based on gel-type, lightly crosslinked polymer skeletons, particularly with regard to reduced reliance on swelling capacity, which allows the use of a wider range of solvents. The work focuses on greener and eco-friendly solvents such as TEP, ACN, IPA, and their mixtures with DMSO to replace toxic solvents such as DMF.

Analysis of Phosphomannomutase-2 Dimer Interface Stability and Heterodimerization with Phosphomannomutase-1.

Phosphomannomutase 2 (PMM2) catalyzes the interconversion of mannose-6-phosphate and mannose-1-phosphate, a key step in the biosynthesis of GDP-mannose for N-glycosylation. Its deficiency is the most common cause of congenital disorders of glycosylation (CDGs), accounting for the subtype known as PMM2-CDG. PMM2-CDG is a rare autosomal recessive disease characterized by multisystemic dysfunction, including cerebellar atrophy, peripheral neuropathy, developmental delay, and coagulation abnormalities.

Bioinformatics-Driven Multi-Factorial Insight into α-Galactosidase Mutations.

Fabry disease is a rare genetic disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A (AGAL), resulting in the accumulation of globotriaosylceramides (Gb3) in tissues and organs. This buildup leads to progressive, multi-systemic complications that severely impact quality of life and can be life-threatening. Interpreting the functional consequences of missense variants in the gene remains a significant challenge, especially in rare diseases where experimental evidence is scarce.

Bioactive Polyketides from spp.: An In-Depth Review of Biosynthesis, Applications, and Current Research Trends.

Polyketides (PKs) are a widespread class of secondary metabolites with recognised pharmacological properties. These molecules are abundantly produced in the marine environment, especially by dinoflagellate-photosynthetic organisms able to produce several PKs, including neurotoxins, cytotoxins, and immunomodulating agents. The biosynthesis of these compounds is driven by a conserved enzymatic process involving polyketide synthase complexes.

The effect of medical cannabis on gastrointestinal symptoms in fibromyalgia and disorders of gut-brain interaction: a patient‑centred real‑world observational study.

Objectives: Fibromyalgia (FM) is frequently associated with gastrointestinal (GI) disorders such as disorders of gut-brain interaction (DGBIs). Current treatments for FM offer limited relief, leading to the exploration of alternative therapies such as medical cannabis. This study evaluates in the impact of Bedrocan® medical cannabis in FM patients and GI symptoms over six months.

Glaser Heterocoupling Reaction for the Synthesis of Enantiomerically Enriched Unnatural α‑Amino Acids Incorporating Asymmetric Diyne Moieties: Mechanistic Insights and Optimization.

The major challenge in synthesizing unsymmetrical 1,3-diynes lies in achieving high selectivity, as competing homocoupling reactions often complicate product isolation. To address this, we employed a Ni-(II) complex of the Schiff base derived from ()-2 -('-benzylprolyl)-aminobenzophenone (BPB) and propargylglycine to optimize the conditions for the Glaser coupling reaction. Systematic variations of the reaction parameters, including solvent, temperature, and reaction time, established an efficient protocol for synthesizing enantiomerically enriched α-amino acids.

The Blue Light-Responsive Lateral Pathway of the Retinohypothalamic Tract Promotes Endocannabinoid-Driven Modulation of Orexin Neurons.

Circadian light influences brain functions in mammals. Photic non-image-forming stimuli are transduced into electrochemical signals by photosensitive retinal ganglion cells containing melanopsin, a selective blue light-responsive photopigment. The hypothalamus receives light-related information via the retinohypothalamic tract (RHT).

strengthens the intestinal barrier: involvement of the endocannabinoidome.

Probiotics have been suggested to ameliorate intestinal epithelial homeostasis and barrier function. They also modulate several mediators and receptors of the expanded endocannabinoid system, or endocannabinoidome (eCBome), potentially explaining their beneficial effects on intestinal function. We aimed to study the effects of probiotic strains on gut barrier functions and the possible involvement of the eCBome in these effects.

π-Turns in Peptides: A Crystal-State Literature Survey.

The results of an analysis on the presence of π-turns, characterized by an i ← i + 5 C=O···H-N intramolecular hydrogen bond, in the X-ray diffraction structures of peptides are discussed. The survey returned a total of 55 π-turn occurrences in linear and cyclic peptides. π-Turns characterized by a helical conformation for residue i + 4, but with a screw sense opposite to that of the three preceding residues, are largely prevailing.

Human Gut Microbes Produce EPA- and DHA-Derived Oxylipins, but not N-Acyl-Ethanolamines, From Fish Oil.

We recently reported that human fecal microbiota colonized in a simulator of the human intestinal microbiome ecosystem (SHIME) process dietary oil from Buglossoides arvensis (Ahiflower), rich in the n-3 polyunsaturated fatty acid (PUFA) stearidonic acid, to the endocannabinoid (eCB)-like N-stearidonoyl-ethanolamine. Here, we assess if human fecal microbiota collected in summer and winter and inoculated in the SHIME (simulating four different intestinal sections; ileum, and ascending, transverse and descending colon) and then treated with fish oil (FO) rich in triglyceride-esterified docosahexaenoic and eicosapentaenoic acids (DHA and EPA, respectively) result in the formation of the corresponding anti-inflammatory and anticancer n-3 PUFA metabolites, including N-acylethanolamines and oxylipins. Effluents were collected every day and analyzed by LC-MS/MS for PUFA metabolites and bacterial and short-chain fatty acids (SCFA) composition during an initial 7-day treatment with vehicle and then a further 7-day treatment with FO (DHA and EPA in equal amounts, 910 mg/day each).

Appearances can be deceiving: differences in FeNO values among COPD and severe asthmatic patients stratified according to peripheral eosinophilic count.

Eosinophilic COPD (eCOPD) and eosinophilic severe asthma (eSA) appear to share relevant clinical features, including responsiveness to steroids and higher exacerbation rates. However, data on the expression of T2-high inflammation biomarkers and, in particular comparison of fractional exhaled nitric oxide (FeNO) levels between the two diseases is lacking. The aim of the current retrospective observational study was to investigate whether FeNO values might differ between eCOPD and eSA patients.

Physiological Muscle Function Is Controlled by the Skeletal Endocannabinoid System in Murine Skeletal Muscles.

The endocannabinoid system (ECS) is known to regulate crucial bodily functions, including healthy muscle activity. However, its precise roles in normal skeletal muscle function and the development of muscle disorders remain unclear. Previously, we developed a tamoxifen-inducible, skeletal muscle-specific CB receptor knockdown (skmCB1-KD) mouse model using the Cre/LoxP system.