Molecules最新文献

Ajuga iva (L.) Schreb. is traditionally used in North African ethnomedicine for the management of inflammation, pain, and fever. The present study aimed to characterize the phytochemical profile of the hydroalcoholic extract of its aerial parts and to evaluate its anti-inflammatory, analgesic, and antipyretic activities using established in vivo models. Preliminary phytochemical screening confirmed the presence of major classes of secondary metabolites, including polyphenols, flavonoids, tannins, and glycosidic compounds. Quantitative assays revealed appreciable levels of total phenolics (26.3 ± 1.2 mg GAE/g extract) and flavonoids (13.5 ± 0.9 mg QE/g extract). In vivo pharmacological evaluation demonstrated significant biological activities, with the highest tested dose (400 mg/kg) producing a marked inhibition of carrageenan-induced paw edema (44.9%), comparable to acetylsalicylic acid. At the same dose, the extract showed pronounced analgesic activity in the acetic acid-induced writhing test, with an inhibition rate of 64.2%, and a significant antipyretic effect in the brewer's yeast-induced fever model, as evidenced by a reduction in rectal temperature. In parallel, molecular docking was employed as an exploratory, hypothesis-generating in silico approach to investigate potential interactions between selected phenolic constituents identified in A. iva and cyclooxygenase-2 (COX-2). Several compounds, including rosmarinic acid, rutin, and apigenin-7-O-glucoside, displayed favorable predicted binding affinities and interactions with key residues of the COX-2 active site. It should be emphasized that molecular docking was used solely as a hypothesis-generating in silico tool and does not constitute direct biochemical evidence of COX-2 inhibition. Overall, these findings indicate that the hydroalcoholic extract of Ajuga iva exhibits notable anti-inflammatory, analgesic, and antipyretic activities in vivo. The in silico docking results provide supportive, predictive molecular insights that may help rationalize the observed bioactivities and encourage further biochemical and mechanistic investigations into this traditionally used medicinal plant.

Δ¹-Pyrroline-5-carboxylate reductase (EC 1.5.1.2; called ProC in most bacteria) is an enzyme of central metabolism that catalyzes the last step of the proline biosynthetic pathways, namely the NADPH-dependent reduction of pyrroline-5-carboxylate (P5C) to L-proline (L-Pro). The enzyme, however, is also active towards other substrates, and these reactions might have physiological relevance. Herein, the substrate versatility of ProC from Escherichia coli was explored as follows. We initially characterized the reverse reaction carried out by ProC, i.e., the formation of P5C from L-Pro. This reaction was easily measurable at pH 10, allowing the determination of the kinetic parameters. Under the same conditions, we then tested the ability of ProC to oxidize a number of L-Pro analogs, confirming that ProC reacts most effectively with analogs containing a simple five-membered ring such as L-thioproline (THP) and 3,4-dehydro-L-proline (DHP). Larger substrates such as L-pipecolate (PIP) reacted with lower efficiency, and the four-membered ring analog, L-azetidine-2-carboxylate (A2C) showed no detectable reactivity and behaved as a weak inhibitor of the ProC reaction. To interpret these results, we built a structural model of ProC and employed this model for a docking analysis of L-Pro and of its analogs. This approach highlighted the presence of a peculiar "three-point interaction", in which the L-Pro carboxylate and amino groups form hydrogen bonds with conserved residues in the binding site, while the substrate ring stacks with the nicotinamide ring of NADP⁺. The L-Pro analogs tried to preserve as much as possible these critical interactions for a correct positioning and a favorable binding. The possibility of an inherent multifunctionality of ProC was further explored by examining the genomic context of the proC gene in a large number of bacterial species.

Planar chiral bisphosphine ligands based on diphenyl [2.2]paracyclophane (PhPhanePHOS) were successfully synthesized in a practical manner in four steps from commercially available 4,12-bisbromo-[2.2]paracyclophane as a new family of bisphosphine ligands. The novel PhPhanePHOS ligands provide high catalytic activity in Pd-catalyzed asymmetric allylic alkylation reactions in preliminary experiments.

Investigating aluminum nitride (AlN) clusters is essential for understanding the properties of bulk AlN materials. The incorporation of hydrogen into AlN clusters represents an effective strategy for structural modification and for tuning their physicochemical properties. In this work, we conducted density functional theory (DFT) calculations on the dynamically stable global-minimum (GM) structure of Al₆N₆H₈. Compared to the precursor Al₆N₆ cluster, the incorporation of eight hydrogen atoms achieves coordination saturation of all aluminum and nitrogen atoms, inducing a structural transformation from a hexagonal prism with D_3d symmetry to a cuboid structure with D_2h symmetry. The HOMO-LUMO gap of the Al₆N₆H₈ cluster is increased by 1.85 eV compared to that of Al₆N₆, indicating a remarkable enhancement in stability. Chemical bonding and natural bond orbital (NBO) charge analyses reveal that the Al-N, Al-H, and N-H bonds are predominantly covalent single bonds, with a degree of ionicity arising from electronegativity differences. The hydrogen atoms bonded to Al and N can be substituted with a series of other atoms or functional groups, thereby further tuning the structures and properties of the clusters. To facilitate future experimental characterization, the infrared spectrum of Al₆N₆H₈ was calculated, which shows an overall blue shift in the Al-N bond's bending and stretching vibrations compared to those in the Al₆N₆ cluster.

Hemp (Cannabis sativa L.) is increasingly valued not only for its fibers and seeds but also for essential oils derived from floral by-products. This study investigates the extraction of essential oils from three hemp floral varieties, Sour Space Candy, Suver Haze 3N, and Pinewalker 3N using hydrodistillation, a widely accepted and efficient method for isolating volatile compounds. The chemical composition and quantification of key volatiles, including α-pinene, β-myrcene, α-humulene, and α-terpineol, were analyzed using gas chromatography-mass spectrometry (GC-MS). In addition to oil extraction, the residual spent biomass was repurposed into pulp fibers using the soda pulping process. Fiber properties such as freeness, viscosity, kappa number, and fiber length were evaluated for papermaking applications. The essential oil yield ranged from 1.24% to 1.86% (w/w), and the spent fiber yield ranged from 37.07% to 55.23%. Handsheets prepared from blends of spent fibers and hemp hurd fibers exhibited tensile indices ranging from 21.87 to 34.98 N·m/g. This dual-valorization approach enhances the economic and environmental value of hemp cultivation, supports sustainable material development, and contributes to the broader adoption of bio-based alternatives.

Prostate cancer is the third-leading cause of cancer death in men. Prostate-specific membrane antigen (PSMA) is a robust biomarker that is expressed in approximately 80% of patients diagnosed with prostate cancer; several theranostic strategies have emerged based upon targeting this biomarker. This report describes a dimeric aptamer complex (DAC) which is selective for PSMA⁺ cancer cells and is amenable to derivatization with additional diagnostic and therapeutic molecules. Confocal microscopy confirmed the selective nature of the DAC for PSMA⁺ LNCAP tumor cells. In addition, the affinity of the DAC for the PSMA protein was determined to be 2.16 ± 0.15 nM using biolayer interferometry (BLI). In proof-of-principle studies, this DAC was biotinylated (BioDAC; A10), complexed with streptavidin (SA), and radiolabeled with the positron-emitting radioisotope zirconium-89 (⁸⁹Zr: t_½ = 78.4 h, β⁺: 22.8%) to form the radiopharmaceutical [⁸⁹Zr]Zr-Df-SA-BioDAC ([⁸⁹Zr]Zr-A12). Acute biodistribution studies revealed elevated levels of radioactivity in PSMA⁺ tumors when compared to PSMA^- tumors. Radioactivity retention in the kidney was high due to the presence of streptavidin, while radioactivity retention in the liver was comparable with that of other radiolabeled aptamer complexes. Accordingly, the data suggests that the radiopharmaceutical will need to be redesigned using a strategy that is not reliant on a biotin-streptavidin paradigm before additional preclinical assessments are made and clinical translation can be attempted.

Although Simarouba glauca DC. has been recognized for its therapeutic properties, its anticancer effects against oral cancer have not been adequately investigated. The present study aimed to evaluate the activity of S. glauca leaf extracts against oral squamous cell carcinoma (OSCC). S. glauca leaves were extracted using solvents of increasing polarity, and the resulting fractions were evaluated for their phytochemical composition, antioxidant activity, and cytotoxic effects. Among all extracts, the S. glauca hexane extract (SGHE) exhibited the most potent anticancer activity against cell lines representing OSCC (CAL-27), cervical cancer (HeLa), and mouse mammary tumors (4T1). Bioactivity-guided fractionation identified D-erythro-Sphinganine as a major constituent present in hexane extract, possibly contributing to anticancer activity. But since the anticancer activity of crude hexane extract is superior compared to isolated D-erythro-Sphinganine, we predict a synergistic interaction among the multiple bioactive compounds present in the crude hexane extract. Hence, further studies were carried out with crude hexane extract. Mechanistic studies have shown that the anticancer activity of hexane extract is due to its ability to (a) alter cell cycle progression, (b) trigger apoptosis, and (c) inhibit cell migration in CAL-27 cells. Overall, these findings indicate that the hexane extract of S. glauca leaf possesses multi-target anticancer potential and warrants further mechanistic and in vivo investigations.

Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) share key molecular features, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and progressive neuronal loss. Increasing evidence indicates that gut dysbiosis and alterations in microbiota-derived metabolites are involved in these processes through multiple pathways along the gut-brain axis. However, while broad compositional changes are well-documented, a critical knowledge gap remains regarding the specific biochemical signal transduction pathways translating dysbiosis into pathology. This narrative review addresses this gap by synthesizing current human and experimental studies addressing gut microbiota alterations in AD, PD, and ALS, with particular emphasis on the biochemical and molecular mechanisms mediated by gut-derived metabolites. Dysbiosis in neurodegenerative diseases is frequently associated with reduced abundance of short-chain fatty acid (SCFA)-producing bacteria and altered metabolism of SCFAs, bile acids, tryptophan-derived indoles, trimethylamine-N-oxide (TMAO), and lipopolysaccharides (LPS). These microbial metabolites have been shown to modulate intestinal and blood-brain barrier integrity, influence Toll-like receptor- and G protein-coupled receptor-dependent signaling, regulate microglial activation, and affect molecular pathways related to protein aggregation in experimental models. In addition, emerging evidence highlights the involvement of oxidative and nitrosative stress, immune-metabolic crosstalk, and altered xenobiotic metabolism in microbiota-host interactions during neurodegeneration. By integrating microbiological, metabolic, and molecular perspectives, this review underscores the important and emerging role of microbiota-derived molecules in neurodegenerative disorders and outlines key chemical and metabolic pathways that may represent targets for future mechanistic studies and therapeutic strategies.

Photobioreactor-based microalgae cultivation offers an integrated approach for nutrient-rich wastewater treatment while producing valuable biomass. One of the main microalgae components is proteins, making them a biotechnological target. In this work, to develop efficient and greener extraction methodologies, aqueous two-phase systems (ATPSs) based on natural deep eutectic solvents (NADESs) were evaluated for one-step protein extraction from microalgae cultivated in swine wastewater. Six ATPSs combining two NADES-betaine:levulinic acid (Bet:2LA) and choline chloride:urea (ChCl:2Urea)-and their individual components (Bet or ChCl) with phosphate salts were compared. Systems {NADES + K₃PO₄ + water} were characterized and reported for the first time. Protein recovery yield (PRY) and selectivity (protein-to-carbohydrate mass ratio, R) were assessed for three extraction times and at room temperature. The ATPS {Bet:2LA + K₃PO₄ + H₂O} achieved a PRY of 16.4% and remarkable selectivity after 30 min (R = 2.17 g·g^-1), with proteins concentrated in the NADES-rich phase, and negligible recovery in the salt-rich phase. Although the maximum PRY (18.2% at 120 min) was achieved with the precursor betaine, the ATPS with Bet:2LA at 30 min offered an optimal balance between efficiency and process time. With a water content of up to 50%, these systems underscore the potential of NADES-based ATPSs as sustainable platforms for protein recovery.

Synthetic gypsum (SG) is produced in massive quantities, yet hazardous impurities limit its reuse. This review summarized the impurity types in various SGs and the corresponding removal methods. Physical methods, such as washing, screening, magnetic separation, and others, exploit solubility and size/density differences to remove soluble salts and particulates. Chemical methods, including acid leaching, precipitation/solidification, and so on, can dissolve or immobilize phosphates, fluorides, and heavy metals. Flotation utilizes the differences in the physicochemical properties of solid surfaces to remove insoluble impurities. The thermal treatment is mainly used to decompose organics and improve whiteness. Microbial methods achieve environmentally friendly cleanup through metabolic leaching or microbially induced carbonate precipitation. The phase-transformation method is a recently developed method that can achieve synergistic effects of deep impurity removal and high-value utilization by reconstructing gypsum crystals to release co-crystallized impurities. Most impurity-removal methods target only a single type of impurity. At present, purifying SG requires a combination of multiple methods, which is not recommended from a cost perspective. Subsequent research on removing impurities from SG should focus on simultaneously removing multiple major impurities in a single process, as well as the synergistic effects between impurity removal and the high-value utilization of gypsum.