Highly Biocompatible Lamellar Liquid Crystals Based on Hempseed or Flaxseed Oil with Incorporated Betamethasone Dipropionate: A Bioinspired Multi-Target Dermal Drug Delivery System for Atopic Dermatitis Treatment.

Purpose: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease that severely impairs patient's life quality and represents significant therapeutic challenge due to its pathophysiology arising from skin barrier dysfunction. Topical corticosteroids, the mainstay treatment for mild to moderate AD, are usually formulated into conventional dosage forms that are impeded by low drug permeation, resulting in high doses with consequent adverse effects, and also lack properties that would strengthen the skin barrier. Herein, we aimed to develop biomimetic lamellar lyotropic liquid crystals (LLCs), offering a novel alternative to conventional AD treatment.

Optimization of Clozapine Treatment: Study of Variables Affecting Response in Uruguayan Patients With Schizophrenia.

Purpose/background: Clozapine is the recommended drug for treatment-resistant schizophrenia. Drug response could be affected by numerous factors such as age, sex, body mass index, co-medication, consumption of xanthine-containing beverages, smoking, and genetic variants of the enzymes involved in clozapine metabolism (CYP1A2, CYP3A4, and, to a lesser extent, CYP2C19 and CYP2D6). This study evaluated genetic and nongenetic variables that may affect clozapine plasma concentrations in Uruguayan patients with schizophrenia.

One Change, Many Benefits: A Glycine-Modified Bacteriochlorin with NIR Absorption and a Type I Photochemical Mechanism for Versatile Photodynamic Therapy.

Difluorinated sulfonamide porphyrin (FPGly) and bacteriochlorin (FBGly), modified by glycine residues, were synthesized and evaluated for photodynamic therapy (PDT). F₂PGly exhibits superior stability and singlet oxygen generation efficiency but features a low-intensity band in the red range (λ = 639 nm). In contrast, FBGly shows a favorable, red-shifted absorption spectrum (λ = 746 nm) that aligns well with phototherapeutic window, facilitating deeper tissue penetration.

Efficient Method of ()-Nicotine Synthesis.

Improved methods for the synthesis of nicotine are of great importance due to the wide range of applications of synthetic nicotine, which is free from contamination with nitrosamines. Herein, we present a four-step chemical synthesis of ()-nicotine, involving the reduction in myosmine, enantiomeric separation of nornicotine, and subsequent methylation of the appropriate enantiomer of nornicotine obtained. The reduction in myosmine was investigated using both electrochemical and chemical approaches, achieving up to 90% yields of pure nornicotine.

Increased Trypanocidal Activity of the Salinomycin Derivative Ironomycin Is Due to ROS Production and Iron Uptake Impairment.

Salinomycin and its derivatives display promising anti-proliferating activity against bloodstream forms of . The mechanism of trypanocidal action of these compounds is due to their ionophoretic activity inducing an influx of sodium cations followed by osmotic water uptake, leading to massive swelling of bloodstream-form trypanosomes. Generally, higher trypanocidal activities of salinomycin derivatives are associated with higher cell swelling activities.

Symmetry Breaking of Electronic Structure upon the π→π* Excitation in Anthranilic Acid Homodimer.

The main purpose of this study is to characterize the nature of the low-energy singlet excited states of the anthranilic acid homodimer (AA) and their changes (symmetry breaking) caused by deformation of the centrosymmetric, ground state structure of AA towards the geometry of the S state. We employ both the correlated ab initio methods (approximate Coupled Clusters Singles and Doubles-CC2 and CASSCF/NEVPT2) as well as the DFT/TDDFT calculations with two exchange-correlation functionals, i.e.

Guanidine Derivative ADS1017, a Potent Histamine H Receptor Antagonist with Promising Analgesic Activity and Satisfactory Safety Profile.

In this study, we selected 12 guanidine derivatives from the previously described ligand library and determined their affinity at histamine H and H receptors (HR and HR, respectively). Moreover, we also checked their intrinsic activity toward HR and muscarinic M, M, and M receptors (MR, MR, and MR, respectively). Since ADS1017 has been proved to be the most selective and highly potent H antagonist in our series, we chose it as the lead structure for further biological evaluation.

Behavior of PGS/apatite foam scaffolds during incubation in SBF, PBS, Ringer's solution, artificial saliva, and distilled water.

Background: Poly(glycerol sebacate) is a polymeric material with potential biomedical application in the field of tissue engineering. In order to act as a biodegradable scaffold, its incubation study is vital to simulate its behavior.

Objectives: This study explores the degradation of porous poly(glycerol sebacate)/hydroxyapatite scaffolds subjected to incubation in various physiological solutions.

Development of bombesin-tubulysin conjugates using multicomponent chemistry to functionalize both the payload and the homing peptide.

Peptide-drug conjugates (PDCs) have recently gained significant attention for the targeted delivery of anticancer therapeutics, mainly due to their cost-effective and chemically defined production and lower antigenicity compared to ADCs, among other benefits. In this study, we designed and synthesized novel PDCs by conjugating new thiol-functionalized tubulysin analogs (tubugis) to bombesin, a peptide ligand with a relevant role in cancer research. Two tubulysin analogs bearing ready-for-conjugation thiol groups were prepared by an on-resin multicomponent peptide synthesis strategy and subsequently tested for their stand-alone anti-proliferative activity against human cancer cells, which resulted in IC values in the nanomolar range.

Studies on the Oxidative Damage of the Wobble 5-Methylcarboxymethyl-2-Thiouridine in the tRNA of Eukaryotic Cells with Disturbed Homeostasis of the Antioxidant System.

We have previously shown that 2-thiouridine (S2U), either as a single nucleoside or as an element of RNA chain, is effectively desulfurized under applied in vitro oxidative conditions. The chemically induced desulfuration of S2U resulted in two products: 4-pyrimidinone nucleoside (H2U) and uridine (U). Recently, we investigated whether the desulfuration of S2U is a natural process that also occurs in the cells exposed to oxidative stress or whether it only occurs in the test tube during chemical reactions with oxidants at high concentrations.

A new chromatographic method for the determination of cysteine, glutathione, homocysteine and Nɛ-homocysteinyllysine isopeptide in human plasma.

Cysteine and glutathione can be applied as therapeutic targets in civilization diseases such as diabetes mellitus and cancers. On the other hand, an elevated concentration of homocysteine, and its metabolites such as homocysteine thiolactone and Nɛ-homocysteinyllysine result in health problems and has been indicated as an independent risk factor for cardiovascular disease and accelerated atherosclerosis. This work describes the first simplified HPLC-UV method that allows simultaneous determination of Nɛ-homocysteinyllysine isopeptide, cysteine, glutathione and homocysteine in human plasma.

Interactions of sphingomyelin with biologically crucial side chain-hydroxylated cholesterol derivatives.

Oxysterols are interesting molecules due to their dual nature, reflecting beneficial and harmful effects on the body. An issue that still needs to be solved is how slight modification of their structure owing to the location of the additional polar group in the molecules affects their biological activity. With this in mind, we selected three side chain-hydroxylated oxysterols namely: 20(S)-hydroxycholesterol (20(S)-OH), 24(S)-hydroxycholesterol (24(S)-OH), and 27-hydroxycholesterol (27-OH), and examined their behavior in mixtures with the bioactive sphingolipid - sphingomyelin (SM).

The Ordered Structures Formed by Janus-like Particles on a Triangular Lattice.

The formation of ordered structures by Janus-like particles, composed of two parts (A and B), with orientation-dependent interactions on a triangular lattice was studied using Monte Carlo methods. The assumed lattice model allows each particle to take on one of the six orientations. The interaction between the A parts of neighboring particles was assumed to be attractive, while the AB and BB interactions were assumed to be repulsive.

Physicochemical and electrical properties of DPPC bilayer membranes in the presence of oleanolic or asiatic acid.

This study aimed to investigate the effect of selected compounds from the group of triterpene sapogenins on model phosphatidylcholine membranes. Two types of biological membrane model systems were used in the work, i.e.

A combination of structure-based virtual screening and experimental strategies to identify the potency of caffeic acid ester derivatives as SARS-CoV-2 3CL inhibitor from an in-house database.

Drug development requires significant time and resources, and computer-aided drug discovery techniques that integrate chemical and biological spaces offer valuable tools for the process. This study focused on the field of COVID-19 therapeutics and aimed to identify new active non-covalent inhibitors for 3CL, a key protein target. By combining in silico and in vitro approaches, an in-house database was utilized to identify potential inhibitors.

Folic acid functionalized Ag@MOF(Ag) decorated carboxymethyl starch nanoparticles as a new doxorubicin delivery system with inherent antibacterial activity.

Considering the benefits of controlled drug delivery in cancer treatment, as well as the importance of biological macromolecules in this area, herein, the pre-synthesized carboxymethyl starch (CMS) was converted to CMS nanoparticles (CMS NPs) in one easy nanoprecipitation way. Thereafter, the Ag@MOF(Ag) was in situ synthesized in the presence of pre-prepared CMS NPs (CMS NPs/Ag@MOF(Ag)). Eventually, the functionalization with folic acid (FA) obtained the CMS NPs/Ag@MOF(Ag)-FA.

Bisdemethoxycurcumin, a novel potent polyphenolic compound, effectively inhibits the formation of amyloid aggregates in ALS-associated hSOD1 mutant (L38R).

Protein misfolding is a biological process that leads to protein aggregation. Anomalous misfolding and aggregation of human superoxide dismutase (hSOD1) into amyloid aggregates is a characteristic feature of amyotrophic lateral sclerosis (ALS), a neurodegenerative illness. Thus, focusing on the L38R mutant may be a wise decision to comprehend the SOD1 disease process in ALS.

Tuning multispectral fluorescence quantum dot-based identification of short-length amyloid β peptides by applying Cu(II) ions.

Currently available methods for detecting amyloid β (Aβ) derivatives are mainly dedicated to determining the long forms Aβ and Aβ. At the same time, the number of physiologically occurring Aβ analogs is much higher, including those truncated at the N- and C-termini. Their identification using standard methods is challenging due to the structural similarity of various Aβ analogs, but could highly benefit from both biomarkers discovery and pathophysiological studies of Alzheimer's disease.

Spasmolytic Activity and Anti-Inflammatory Effect of Novel Mebeverine Derivatives.

: Irritable bowel syndrome (IBS) has a major negative influence on quality of life, causing cramps, stomach pain, bloating, constipation, etc. Antispasmodics have varying degrees of efficacy. Mebeverine, for example, works by controlling bowel movements and relaxing the muscles of the intestines but has side effects.

Single- vs. two-stage fermentation of an organic fraction of municipal solid waste for an enhanced medium chain carboxylic acids production - The impact of different pH and temperature.

Single-stage fermentation was characterized by low medium chain carboxylic acids concentrations and different mesophilic temperatures had little effect on the process performance, whereas thermophilic conditions and pH 5.5 led to lactate and ethanol accumulation. Two-stage fermentation enabled almost twofold increase in the caproate productivity, that reached 0.

Nanoscale Structures of Tough Microparticle-Based Films Investigated by Synchrotron X-Ray Scattering and All-Atom Molecular-Dynamics Simulation.

In this study, the nanoscale structures of microparticle-based films are revealed by synchrotron small-angle X-ray scattering (SAXS) and all-atom molecular-dynamics (AA-MD) simulations. The microparticle-based films consisting of the simplest acrylate polymer microparticles are applied as a model because the films are formed without additives and organic solvents and exhibit high toughness properties. The characteristic interfacial thickness () obtained from the SAXS analysis reflects the mixing degree of polymer chains on the microparticle surface in the film.

Mechanisms of dissolution and crystallization of amorphous glibenclamide.

Amorphous solid dispersions enhance the dissolution and oral bioavailability of poorly water-soluble drugs. However, the link between polymer properties and formulation performance has not been fully clarified yet. We studied the effect of hydroxypropyl cellulose (HPC) polymers molecular weight (M) on the storage stability, dissolution kinetics and supersaturation stability of spray-dried amorphous glibenclamide (GLB) formulations.