Bruňáková K, Bálintová M, Čmelík R, Moravcová D, Mati R, Henzelyová J, Petijová L.
Nat Prod Res
PMID:42001504
Free PMC article
Liquid chromatography with diode-array and mass spectrometric detection (HPLC-DAD, LC-MS) is essential for anthraquinone (AQ) analysis, particularly for glycosides lacking standards. While hypericins in Hypericum are well studied, AQ diversity and its relationship to hypericin biosynthesis remain insufficiently characterised. We developed an optimised workflow for profiling emodin- and skyrin-related AQs and their glycosides in Hypericum species. A liquid-liquid extraction enabled efficient recovery of aglycones and glycosides. HPLC-DAD was optimised for selective detection, ion-trap LC-MS supported structural elucidation, and acid hydrolysis confirmed glycosylation patterns. Analysis of eleven Hypericum species revealed O -pentosides and O -hexosides of skyrin and oxyskyrin, the latter reported here for the first time in the genus and restricted to hypericin-producing species. Correlation analyses showed coordinated accumulation of emodin, skyrin derivatives, and hypericins, consistent with associative relationships within the naphthodianthrone-related metabolic network. The approach improved analytical resolution and highlighted interspecific variation relevant to phytochemical and biosynthetic studies.
Kim-Fu ML, Logan IE, Peeters Weem J, Sanchez JV, Hernandez EE, Reardon PN, Rochefort WE, Field JA.
Anal Chem
PMID:42002899
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An in situ nuclear magnetic resonance (NMR) tube extraction coupled with fluorine-19 ( 19 F) NMR spectroscopy was developed to quantify extracted fluorine. A solid-liquid extraction of Viton A was performed in situ in an NMR tube whereby an organic solvent was added to solid cross-linked Viton A (10 mg) that was positioned below the detection region of the NMR probe. The extracted fluorine was measured while relying on diffusion of fluorine-containing molecules from the fluoropolymer into the solvent. The in situ approach was used to correlate extraction efficiency as a function of polymer swelling. Permeation, calculated from swelling, was 2-fold greater using acetone compared to methanol. Acetone greater extracted fluorine concentration (ng F/g fluoropolymer) after 302 min of extraction. This method was also applied to a Viton A cord, a Viton O-ring, and polytetrafluoroethylene. Analysis by 19 F diffusion-ordered spectroscopy NMR indicated that the extracted fluorine observed by 19 F NMR was composed of non-cross-linked Viton A liberated from the polymer matrix. For individual PFAS analysis, liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF) showed increased extraction of perfluorooctanoic acid (PFOA) and perfluorohexanoic acid (PFHxA) as a function of time and swelling. Although it appeared that acetone extracted PFOA and PFHxA with greater efficiency than methanol, concentrations were not statistically significantly different. Thus, swelling with methanol was sufficient for extracting nonpolymeric molecules from Viton A. Therefore, measures of extracted fluorine by 19 F NMR or other nondiscriminatory methods should not be interpreted as individual PFAS, without LC-QTOF confirmation. Our in situ approach minimizes the need for ex situ sample preparation and can be applied to other in situ NMR experiments such as solid leaching or solid-liquid partitioning.
Thakur A, Rana M, Vanjani S, Liou KC, Taliyan R, Nepali K, Yang CH.
Med Res Rev
PMID:42001306
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Alzheimer's disease (AD) is a debilitating neurodegenerative condition characterized by progressive cognitive impairment, memory deterioration, and neuronal dysfunction. Its complex pathophysiology involves multiple interlinked processes, including amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, synaptic dysfunction, and cholinergic deficits. Current FDA-approved therapies provide only symptomatic relief and fail to halt disease progression, highlighting the urgent need for more effective treatment strategies. This review provides a comprehensive overview of the pathological mechanisms underlying AD and the emerging therapeutic targets for the design of tractable anti-AD scaffolds, namely, acetylcholinesterase, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), glycogen synthase kinase-3β (GSK3β), dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), histone deacetylases (HDACs), and soluble epoxide hydrolase (sEH). Emphasis is placed on the paradigm shift from single-target therapies to multitarget-directed ligands (MTDLs), which are increasingly recognized as promising tools to tackle AD's multifactorial pathology. We also discuss recent advances in medicinal chemistry and structure-guided drug discovery campaigns aimed at developing pharmacologically optimized, BBB-penetrant MTDLs. By consolidating mechanistic insights with therapeutic innovation, this review aims to facilitate the development of next-generation therapeutics with enhanced efficacy and disease-modifying potential in AD.
Huang XY, Yu CQ, Wang X, Guo Z, Jin CH.
Expert Opin Ther Pat
PMID:41984152
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Introduction Activin receptor-like kinase 5 (ALK5) is a pivotal component of the transforming growth factor β (TGF-β) signaling pathway. Currently, 10 ALK5 inhibitors are under clinical investigation, with numerous others in preclinical stages, demonstrating broad therapeutic potential. However, no systematic review of ALK5 inhibitor-related patents has been conducted to date. Therefore, this study systematically reviews patents related to ALK5 inhibitors from 2013 to the present, providing a theoretical basis for discovering structurally novel, safe, and effective ALK5 inhibitors. Areas covered This paper briefly outlines ALK5 inhibitors currently in clinical development and ALK5-related patents published since 2013, retrieved through databases such as Google Patents, CAS SciFinder and PatSnap. Expert opinion ALK5 inhibitors have garnered significant interest in recent years for the treatment of TGF-β-related diseases, with encouraging outcomes observed in clinical trials. However, certain structural classes have been associated with adverse effects such as cardiotoxicity and bone toxicity. This review consolidates patent literature on ALK5 inhibitors, offering insights to support the development of novel, highly efficient, and low-toxicity inhibitors with improved pharmacokinetic profiles.
Rawat V, Sharma S, Kumar A, Paul V.
Crit Rev Anal Chem
PMID:41999236
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Microplastic (MP) contamination in food has emerged as a critical global concern due to the extensive use of plastics and their persistence in the environment. These particles, originating from degradation of larger plastics or direct industrial sources, have been detected in diverse food matrices, including seafood, salt, bottled water, and dairy products, posing potential health risks to consumers. This review critically evaluates the analytical techniques used to detect, identify, and quantify MPs in food. Conventional methods such as microscopy (light, fluorescence, SEM), spectroscopy (FTIR, Raman), and thermal analysis (TGA, DSC, Py-GC/MS) are discussed with respect to their sensitivity, specificity, and applicability. Chromatographic and mass spectrometric techniques, including LC-MS (Liquid Chromatography-Mass Spectrometry) and MALDI-MS (Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry), offer molecular-level insights but require complex sample preparation. Emerging tools such as nanoparticle-based sensors, DNA (Deoxyribonucleic acid) biosensors, microfluidic lab-on-a-chip devices, and AI-assisted imaging represent significant advances toward rapid, sensitive, and portable detection. Despite progress, challenges persist due to heterogeneous food matrices, lack of standardized protocols, and limited regulatory frameworks. The review emphasizes the need for harmonized methodologies, interdisciplinary research, and innovative detection strategies to ensure reliable monitoring of MPs and safeguard food safety.
