hyoscyamine sulfate (IBStat)

From crude extracts to purified fractions: Tracking sulfate preservation, antioxidant loss, and nanostructures by X-ray scattering of Hokkaido brown algae fucoidans.

Kumagai Yuya Y, Mune Martin Alain Mune MAM, Akita Shingo S, Sajeevan Shilja S et al.

Fucoidan shows promise for food and therapeutic applications; however, inadequate purification leads to inconsistent composition and over-claimed bioactivity. This study rigorously fractionated eight brown algae species from Hokkaido, Japan, using anion-exchange chromatography to generate three primary fractions (FN1, FN2, and FN3). While fractionation enriched sulfate content, it resulted in a >90% reduction in measured antioxidant activity. Multivariate analysis identified the interaction between sulfate and saccharide contents as the principal determinant of this residual activity. Makombu-derived FN3 was then enzymatically digested, treated with activated charcoal, and ultrafiltered to yield FN3 UF, which contained 48.9% sulfate and negligible glucuronic acid, as determined by high-performance anion-exchange chromatography with pulsed amperometric detection. Overall results suggest that the high activity typically reported is largely extrinsic, driven by co-extracted impurities, whereas the true intrinsic activity is trace (~1 μg/mg). Synchrotron small-angle X-ray scattering revealed that this refinement triggers an expansion of the Bragg distance from 12.6 nm (alginate-rich FN1) to 21.7 nm (sulfated FN3), providing the first direct physical evidence that sulfate-driven electrostatic repulsion governs fucoidan's nanostructural organization in solution. These findings establish a previously undocumented physical baseline, proving that rigorous chemical refinement is a mandatory prerequisite for reliable structure-function evaluations of fucoidan.

Unraveling the pleiotropic functions of Rhizobium rhizogenes rolB and rolC genes on phenotype, secondary metabolism, and drought tolerance in Atropa belladonna.

Liang Shanshan S, Mu Dehui D, Ma Yihan Y, Xu Guoju G et al.

Atropa belladonna L. (Solanaceae) is a significant source of the pharmacologically important tropane alkaloids (TAs), particularly hyoscyamine and scopolamine. Although rolB and rolC from Rhizobium rhizogenes are known to enhance plant secondary metabolism, their functional specificities and combined actions in TAs biosynthesis remain unclear. Here, we generated transgenic A. belladonna overexpressing 35S::rolB, 35S::rolC, and 35S::rolB + rolC to systematically investigate their effects on TAs accumulation, plant morphology, and drought tolerance. Co-expression of rolB and rolC exhibited metabolic antagonism, with TAs levels significantly lower than in rolC single transgenic plants, further establishing rolC as the primary regulator of this pathway. Phenotypic analysis revealed divergent effects: rolB increased leaf size and promoted root growth, whereas rolC caused dwarfism, early flowering, and male sterility; double transgenic plants displayed exacerbated growth inhibition. Notably, rolC-expressing plants showed improved drought performance via combined morphological and antioxidant adjustments. Mechanistically, both genes upregulated key biosynthetic genes, with rolC regulating a broader set. Protein interaction assays revealed that RolC directly interacts with TRI, calmodulin (CaM1/CaM7), and the brassinosteroid signaling component BSK. A root-specific transcription factor, AbbHLH30, was identified as a candidate downstream component of the RolC-CaM1 module, with the capacity to activate H6H expression in transient assays. This study provides a mechanistic basis for understanding rol gene functions and offers specific molecular targets for engineering TAs production in A. belladonna.

Exploratory Study on Colistin Sulfate Pharmacokinetics and Safety in Critically Ill Elderly Patients.

Xu Aochao A, Xiong Xiaomiao X, Zhang Na N, Qu Geping G et al.

The rise of multidrug-resistant Gram-negative bacteria has made polymyxins vital last-line therapies. However, its pharmacokinetics in elderly patients remain poorly characterized, which hinders dosing optimization to balance efficacy and toxicity risks in this vulnerable population. A prospective, single-center observational study was conducted in elderly (≥65) intensive care unit (ICU) patients who received colistin sulfate therapy. Blood samples were collected prior and post-dose time points. Plasma concentrations of colistin sulfate were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic (PK) parameters were calculated via non-compartmental analysis. Treatment-emergent adverse events and laboratory parameters were systematically recorded for safety evaluation. Thirteen patients with MDR gram-negative infections were included and all received colistin sulfate-based combination therapy; 84.6% achieved anti-infective efficacy. Compared with previously reported data in healthy individuals at 50 MIU q12h, elderly patients demonstrated significantly higher AUC0-12h (9.62 ± 3.58 vs. 5.33 ± 0.71 mg·h/L, p < 0.05), prolonged T1/2 (25.84 ± 25.19 vs. 4.53 ± 1.22 h, p < 0.05), and larger Vd (87.57 ± 74.40 vs. 17.32 ± 2.52 L, p < 0.05). Target attainment(AUC0-24h/MIC ≥ 50) probability was ≥ 80% only at MIC ≤ 0.25 mg/L, dropping to ≤ 20% at MIC ≥ 0.5 mg/L. Serum creatinine elevations occurred during colistin therapy and returned to baseline after discontinuation 7-14 days, while liver function parameters remained stable throughout. Colistin sulfate therapy in critically ill elderly ICU patients demonstrates elevated systemic exposure with reversible nephrotoxicity, necessitating pharmacokinetic-guided dosing strategies individualized to renal function, therapeutic drug monitoring, and clinical severity.

csRNA and heparan sulfate : cell surface ribonucleoproteins regulate HS-mediated signaling.

Li Jinlin J, Ling Jiaxin J