theophylline (Theocron / Theophylline SRT / Duraphyl)

Combined cord blood metabolomic and clinical signatures discriminate small for gestational age neonates in preeclampsia.

Zhang Luhan L, Huang Weibo W, Xue Shuyuan S, Chi Xiaolan X et al.

Preeclampsia (PE) subjects the fetus to a hostile intrauterine environment and elevates the risk of small for gestational age (SGA). The link between cord blood metabolic signs and PE exposure is still unclear. This connection may affect fetal growth. We did untargeted metabolomics profiling of cord blood. This involved 37 pregnancies with preeclampsia (PE) and 48 control pregnancies. We used liquid chromatography-mass spectrometry for the analysis. Researchers examined metabolites that showed differential expression. They also analyzed pathway enrichment. We used Spearman's correlation to assess associations between metabolites and clinical indicators, including birth weight. We created a discriminative model for SGA. It combines metabolic features and clinical variables. In the PE group, 205 metabolites changed significantly. Of these, 82 were upregulated and 123 were downregulated. Caffeine metabolism, lysine biosynthesis, and sulfur metabolism were the top three pathways affected. Among the dysregulated metabolites, 2-oxoadipic acid is important in lysine breakdown. It showed a strong negative link with birth weight (r = -0.396, P < 0.001). Xanthine had positive links to gestational age at delivery (r = 0.292, P = 0.007) and birth weight (r = 0.219, P = 0.044). Lysine was positively correlated with maternal BMI at delivery (r = 0.414, P < 0.001). Caffeine metabolites, like paraxanthine, theobromine, and theophylline, were enriched together. However, none showed a significant link to birth weight. The SGA discriminative model reached an AUC of 0.896 (P < 0.01). PE greatly changes the cord blood metabolome. This has a primary impact on caffeine, lysine, and sulfur metabolism. 2-Oxoadipic acid is linked to fetal growth restriction. Combining cord blood metabolic signatures with clinical data makes a strong model. These findings reveal metabolite-level disturbances that may help elucidate the metabolic basis of impaired fetal growth in preeclampsia.

Low-dose theophylline in mild-to-moderate COPD: A physiological signal without clear clinical benefit?

Lin Yijuan Y, Li Feng F, Huang Yixun Y

An aptamer-regulated CRISPR/Cas12a system based on split crRNA for theophylline and tobramycin detection.

Liu Jinming J, Li Le L, Tang Ziwen Z, Li Yachen Y et al.

Most existing CRISPR/Cas12a methods for small molecules detection employ DNA aptamers as an intermediary, while RNA aptamers remain underexplored. The conventional CRISPR/Cas12 system offers limited programmability due to its partially conserved crRNA sequence. In this study, we developed an aptamer-regulated CRISPR/Cas12a system based on split crRNA. We divided the full crRNA into a crRNA handle segment (RH) and a crRNA spacer segment that is identical to the RNA aptamer sequence of target (RS-Apt). RS-Apt was endowed with dual functions: activating the activity of Cas12a and binding to target small molecules, ingeniously linking non-nucleic acid targets with the CRISPR system. The strong affinity between the target and RS-Apt reduces the amount of RS-Apt available to participate in the CRISPR system, resulting in a decrease in the fluorescence signal of the system. Within 1.5 h, the system for theophylline (TP) exhibited a linear range from 50 nM to 200 µM and a detection limit (LOD) of 2 nM, while the system for tobramycin (TOB) showed a linear range of 200 nM to 100 µM with an LOD of 63 nM. Notably, visual semi-quantitative detection of TP and TOB was achieved via lateral flow strips. Moreover, the system achieved satisfactory recovery and visual detection of TP using lateral flow strips in TP-spiked serum samples. This system can detect different targets simply by changing the sequence of the RS-Apt and activator, without the need for complex sequence design of the chains or large-scale instruments, providing a new strategy for CRISPR/Cas12a in the detection of small molecules.

Elucidation of hydrogen bonding networks in theophylline cocrystals by 1H-detected 17O and 14N solid-state NMR spectroscopy.

Bequette Joseph P JP, Riemersma Kipper K, Carnahan Scott L SL, Paterson Alexander L AL et al.

Determining hydrogen bonding networks and proton positions in pharmaceutical cocrystals remains challenging, particularly for microcrystalline materials and systems involving strong hydrogen bonds and partial proton transfer. Here, we demonstrate a strategy that combines fast magic-angle spinning (MAS) solid-state NMR with 1H-detected 17O → 1H and 1H{14N} heteronuclear correlation experiments to directly probe hydrogen bonding interactions in theophylline-carboxylic acid cocrystals. Facile 17O enrichment of carboxylic acid coformers (benzoic, oxalic, maleic, and malonic acids) was achieved by isotope exchange with 17O-enriched water under mild conditions. Isotope exchange reactions can be easily monitored by 17O solution NMR spectroscopy. Two-dimensional 17O → 1H D-RINEPT and 1H{14N} D-HMQC spectra recorded with variable dipolar recoupling times enable assignment of overlapping 1H resonances and provide site-specific identification of intermolecular hydrogen bonds between theophylline and carboxylic acid coformers. High magnetic field SSNMR experiments (up to 25.8 T) further enhance 17O spectral resolution and enable resolution of overlapping 17O resonances associated with distinct hydroxyl, carbonyl, and dynamically exchanging oxygen environments. Complementary 1H spin-diffusion and dipolar double-quantum experiments corroborate intermolecular contacts and confirm cocrystal formation. Experimental 17O and 14N solid-state NMR parameters are in good agreement with Gauge Including Projector Augmented Wave (GIPAW) density functional theory (DFT) calculations. Together, these results establish a practical multinuclear SSNMR approach for identifying hydrogen bonding networks in pharmaceutical cocrystals and other multicomponent organic solids.