bims-supasi 2025-12-21 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2025–12–21
fourteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Synthesis of Lipid-Conjugated Heparan Sulfate Mimetics and Their Effect on Complement Inhibition.
Targeting the gut-vascular axis: Chondroitin sulfate C enhances microbial hydrogen sulfide production to alleviate hypertension.
Systematic optimization of fed-batch fermentation for enhanced heparosan production in engineered Corynebacterium glutamicum.
A Competitive Immunoassay for Dehydroepiandrosterone Sulfate in Dried Blood Spots.
The glycosaminoglycan oncofetal chondroitin sulfate represents a novel target for antibody drug-conjugate therapy for AML.
Cell-surface RNA forms ternary complex with RNA-binding proteins and heparan sulfate to recruit immune receptors.
The evaluation of indoxyl sulfate in the general population in Kanegasaki Iwate: A cross-sectional study (KANEGASAKI study).
Saffold virus exploits integrin αvβ8 and sulfated glycosaminoglycans as cooperative attachment receptors for infection.
Quantitative profiling of aromatic amino acids and their host-microbial co-metabolites in human urine via UPLC-MS/MS.
Maternal serum steroid hormones in vaginal delivery and caesarean section.
A sulfonated cartilage interpenetrating polymer network reinforces and protects the extracellular matrix of degraded cartilage.
A Novel Hypothesis for the Protective Rise in Cholesterol Sulfate Against Lipid Metabolic Disorders.
Analysis of propranolol and its metabolites in postmortem human solid tissues and body fluids: LC-MS/MS approach with the standard addition method applied to a forensic case.
Comparison of the Biologic Activity of Different Species of Heparin.

Chembiochem. 2025 Dec 17. e202500262

Synthesis of Lipid-Conjugated Heparan Sulfate Mimetics and Their Effect on Complement Inhibition.

Ivan M Ryzhov, Alexander B Tuzikov, Inna S Popova, Ye Li, Neda Salimi-Afjani, Sam Spijkers-Shaw, Phillip M Rendle, Robert Rieben, Nicolai V Bovin, Olga V Zubkova.

  Heavily sulfated clusters of maltose are designed as mimetics of heparan sulfate (HS), exhibiting diverse biological activity properties of HS. Herein, the synthesis of three function-spacer-lipid (FSL) constructs containing mono, di, and tri sulfated maltoses is reported. FSLs are a class of synthetic glycolipids, the key features of which are simplicity of synthesis and capacity to integrate into cell membranes with sustained retention. A copper-catalyzed azide-alkyne cycloaddition click reaction is employed for the conjugation of the sulfated maltose entities with the respective spacer-lipid block because acylation with activated esters failed to provide the desired products. One FSL construct, featuring a single sulfated maltose unit conjugated to the lipid, demonstrated dose-dependent inhibition of complement activation in a cellular system, with maximal efficacy observed at 15 µg mL-1. These findings highlight the potential of FSL-based HS mimetics for modulating immune responses.

Keywords:  click chemistry; clusters; complement inhibition; glycolipids; sulfated maltose

DOI:  https://doi.org/10.1002/cbic.202500262
Int J Biol Macromol. 2025 Dec 16. pii: S0141-8130(25)10284-5. [Epub ahead of print] 149727

Targeting the gut-vascular axis: Chondroitin sulfate C enhances microbial hydrogen sulfide production to alleviate hypertension.

Naishi Chen, Liying Ma, You Kang, Xinjiao Quan, Yujuan Zhao, Ge Yang, Yansong Gao, Shengyu Li, Zijian Zhao.

  Hypertension remains a major global health challenge, often associated with vascular remodeling, oxidative stress, inflammation, and gut microbiota dysbiosis. In this study, we explored the effects of chondroitin sulfate C, a special bioactive substance, on blood pressure regulation and its potential mechanism involving the gut-vascular axis. Hypertensive rats induced by L-NAME were treated with chondroitin sulfate C, which resulted in significant reductions in both systolic and diastolic blood pressure, as well as improvements in aortic histology. Mechanistically, chondroitin sulfate C mitigated oxidative stress, as evidenced by increased antioxidant enzyme activity and decreased ROS production. Inflammatory markers, including TNF-α and adhesion molecules, were significantly reduced. Notably, chondroitin sulfate C promoted the growth of Desulfovibrio in the gut, leading to increased H2S production, which activated the AKT/eNOS pathway, restored NO levels, and enhanced vasodilation. These findings suggest that gut-derived H2S plays a critical role in blood pressure regulation and highlight the therapeutic potential of chondroitin sulfate C in hypertension management.

Keywords:  Chondroitin sulfate C; Gut-vascular axis; Hydrogen sulfide; Hypertension

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.149727
Int J Biol Macromol. 2025 Dec 15. pii: S0141-8130(25)10244-4. [Epub ahead of print] 149687

Systematic optimization of fed-batch fermentation for enhanced heparosan production in engineered Corynebacterium glutamicum.

Qiang Xue, Ruoxuan Wu, Jing Yu, Hui Cao, Tianwei Tan.

  Heparin, a highly sulfated glycosaminoglycan derived from heparan sulfate (HS), is widely employed as a clinical anticoagulant and antithrombotic agent. Low-molecular-weight heparin (LMWH, 4-5 kDa), a derivative of heparin, provides improved safety, ease of administration, and reduced need for monitoring, making it the preferred anticoagulant in modern medicine. However, LMWH produced through animal extraction or chemical synthesis are associated with inherent limitations (e.g., batch variability, contamination risk, cost, scalability). Enzymatic chemo-synthesis modification of heparosan, a heparin precursor polysaccharide, has recently emerged as a promising strategy for producing heparin-based therapeutics. In this study, we optimized the fed-batch fermentation process to enhance the biosynthesis of LMWH in engineered Corynebacterium glutamicum. Compared to batch fermentation, fed-batch cultivation significantly improved both cell biomass and heparosan titer. Among the strategies tested, variable-rate feeding achieved the highest production, resulting in a 3.93-fold increase. Optimization of agitation speed identified 500 rpm as the most favorable condition, maintaining dissolved oxygen (DO) at 15-30 % and leading to a maximum heparosan titer of 8.02 g/L. Maintaining glucose levels within 1-10 g/L effectively supported cell growth while maximizing heparosan biosynthesis. The product was subsequently purified through a multi-step process, achieving 98.4 % apparent purity.

Keywords:  Corynebacterium glutamicum; Fed-batch fermentation; Heparosan; Process optimization; Purification

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.149687
Am J Hum Biol. 2025 Dec;37(12): e70182

A Competitive Immunoassay for Dehydroepiandrosterone Sulfate in Dried Blood Spots.

Elena Hinz, Aaron A Miller, Herman Pontzer.

  Dehydroepiandrosterone sulfate (DHEA-S) is a steroid hormone commonly measured to assess neuroendocrine activity related to HPA-axis function, stress physiology, and broader health outcomes, with significance for Human Biology research. To facilitate research assessing DHEA-S concentrations using minimally invasive sample collection methods, we present validation results for a competitive immunoassay to quantify DHEA-S in dried blood spots (DBS) collected via finger prick. Results demonstrate acceptable levels of inter- and intra-assay variation, linearity of dilution, lowest limit of detection, and agreement between matched DBS and plasma samples (Pearson's R = 0.96). The protocol presented here using a modified commercially available assay kit offers a practical alternative for evaluating DHEA-S in a wide range of settings.

Keywords:  DHEA‐S; ELISA; dried blood spots

DOI:  https://doi.org/10.1002/ajhb.70182
Blood. 2025 Dec 17. pii: blood.2024028147. [Epub ahead of print]

The glycosaminoglycan oncofetal chondroitin sulfate represents a novel target for antibody drug-conjugate therapy for AML.

Joana Mujollari, Montserrat Estruch Alrich, Priya Khadgawat, Swati Choudhary, Tobias Gustavsson, Robert Dagil, Norbert Redlinger, Caroline Løppke, Elena Vidal Calvo, Mie Anemone Nordmaj, Thor Grundtvig Theander, Olaf Heidenreich, Yen Nguyen, Shuyu Qin, Anne Louise Tølbøll Sørensen, Kristen Grønbæk, Bo T Porse, Brigitte Kircher, Jan Mueller, Mette Agerbæk, Ali Salanti, Kim Theilgaard-Mönch.

Antibody-drug conjugates (ADCs) have emerged as promising targeted therapies in acute myeloid leukemia (AML). However, most ADCs exhibit off-target binding to normal hematopoietic stem and myeloid progenitor cells, resulting in adverse hemato-toxicity and narrow therapeutic windows, limiting their clinical application to young and fit AML patients eligible for intensive curative therapies. Proteoglycans with high levels of the glycosaminoglycan oncofetal chondroitin sulfate (ofCS), are abundantly expressed in solid cancers while being absent or lowly expressed in normal adult tissues. Here, we report high ofCS levels on bone marrow (BM) cells of AML patients and AML patient-derived xenografts (PDXs), while BM cells of healthy subjects showed low or undetectable ofCS levels. Consistently, an anti-ofCS antibody demonstrated binding and internalization into AML cells, and anti-ofCS ADCs effectively killed AML cells in vitro. Moreover, anti-ofCS ADC treatment significantly prolonged survival of AML PDXs compared to controls and was associated with low toxicity. Hence, anti-ofCS ADC could represent an effective therapy with acceptable toxicity applicable for all AML patients, including those ineligible or unresponsive to current intensive curative therapies. In conclusion, our study for the first time demonstrates that a glycosaminoglycan like ofCS represents a druggable target for development of effective antibody-based AML therapies.

DOI: https://doi.org/10.1182/blood.2024028147
Mol Cell. 2025 Dec 18. pii: S1097-2765(25)00937-2. [Epub ahead of print]85(24): 4633-4650.e11

Cell-surface RNA forms ternary complex with RNA-binding proteins and heparan sulfate to recruit immune receptors.

Zeshi Li, Bhagyashree S Joshi, Hongbo Yin, Ruud H Wijdeven, Azen Koç, Dick W Zijlmans, Irene Santos-Barriopedro, Hailiang Mei, Wei Wu, Milad Shademan, Filip M Zawisza, Eric Bos, Pradeep Chopra, Marvin E Tanenbaum, Thomas H Sharp, Michiel Vermeulen, Vered Raz, Chirlmin Joo.

  Recent discoveries have shown the presence of ribonucleic acid (RNA) on the cell surface, defying the view that RNA only functions intracellularly. However, how RNA is presented on the cell surface and what its biological relevance is are poorly understood. We established Toll-like receptor 7 (TLR7) as a cell-surface RNA (csRNA) probe. Employing it in a genome-wide knockout screening, we identified heparan sulfate (HS) as a crucial factor for csRNA presentation. Cell-surface proximity labeling revealed that HS-associated csRNAs (hepRNAs) are in the vicinity of RNA-binding proteins (RBPs). These observations led us to a model wherein cell-surface HS, RNA, and RBP form ternary complexes, validated by our spatio-selective RNA-protein crosslinking technology in a TLR7-orthogonal manner. We further revealed the identities of hepRNA and found that they can recruit the immune receptor killer cell immunoglobulin-like receptor 2DL5 (KIR2DL5), potentially enhancing receptor-ligand interactions. Employing human cell lines, our findings lay the groundwork for investigating how cell-surface ribonucleoproteins contribute to immune modulation.

Keywords:  RNA-binding protein; RNA-protein crosslinking; Toll-like receptor 7; cell-surface RNA; genome-wide screening; heparan sulfate; immune receptor; proximity labeling; quantitative proteomics; ribonucleoprotein

DOI:  https://doi.org/10.1016/j.molcel.2025.11.020
PLoS One. 2025 ;20(12): e0332655

The evaluation of indoxyl sulfate in the general population in Kanegasaki Iwate: A cross-sectional study (KANEGASAKI study).

Mizuki Hisano, Takaya Abe, Kie Sekiguchi, Eri Hakozaki, Fumiaki Takahashi, Kozo Tanno, Toshikazu Abe, Kenichi Takeuchi, Toru Maruyama, Ryo Takata, Wataru Obara.

Chronic kidney disease (CKD) significantly impacts global health. Renal function is evaluated using urinary albumin-creatinine ratio (U-Alb/Cr ratio) and estimated glomerular filtration rate (eGFR). However, these parameters reflect the damage that has already occurred, limiting their utility for early detection. Therefore, novel biomarkers that can detect CKD before functional decline are urgently needed. Kidney fibrosis is an important pathologic feature of CKD and precedes functional impairment, highlighting its potential as an early indicator of CKD. Indoxyl sulfate (IS), a gut-derived uremic toxin, promotes kidney fibrosis and accelerates CKD progression, highlighting its strong potential as a biomarker for early CKD detection. As most studies on IS focused on the state of impaired renal function, the trend of IS in early-stage or preclinical CKD is unclear. Furthermore, quantifying IS in clinical practice is problematic because it's primarily measured through high-performance liquid chromatography. A recently developed enzyme method has simplified large-scale IS measurement. Identifying the associated factor with IS, we measured serum IS using enzyme method. We analyzed 674 participants who received specific health checkups and had an eGFR of ≥60 mL/min/1.73 m2 (non-CKD) after obtaining their consent. In addition to standard examinations, we measured serum IS and administered a questionnaire about the frequency of defecating conditions. In this study, we investigated the level of the serum IS in association with the background characteristics of non-CKD participants. For the first time in this study, the median serum IS level was 3.7 (interquartile range, 2.7-5.0) µmol/L in individuals with non-CKD participants, and the linear regression analysis revealed that serum IS was significantly correlated with age, eGFR, and constipation. These findings suggest that IS accumulation begins before overt renal dysfunction, supporting its potential as an early biomarker for CKD. Although further longitudinal studies are warranted, our results highlight the clinical relevance of IS in the early detection and intervention of CKD.

DOI: https://doi.org/10.1371/journal.pone.0332655
Nat Commun. 2025 Dec 15.

Saffold virus exploits integrin αvβ8 and sulfated glycosaminoglycans as cooperative attachment receptors for infection.

Takako Okuwa, Toshiki Himeda, Kyousuke Kobayashi, Namiko Nomura, Kouichi Utani, Satoshi Koike, Akira Nakamura, Masaya Higuchi.

Saffold virus (SAFV), a member of the species Cardiovirus saffoldi within the Picornaviridae family, causes acute respiratory and gastrointestinal illnesses as well as hand, foot, and mouth disease. It is also suspected to be associated with neuronal disorders, such as encephalitis and meningitis, in severe cases. Despite its clinical significance, the virus-host interactions underlying SAFV pathogenicity remain largely unknown. Using a genome-wide CRISPR-Cas9 knockout screen, we identify the following receptors for SAFV infection: sulfated glycosaminoglycans (GAGs) and integrin αVβ8. Single knockouts of SLC35B2, an essential gene for sulfated GAG synthesis, or the integrin genes ITGAV or ITGB8 partially reduce SAFV-3 and SAFV-2 susceptibility in HeLa cells, and a double knockout confers complete resistance. Furthermore, we demonstrate that SAFV-3 virions bind directly to sulfated GAGs and integrin αVβ8. Based on these findings, we propose a model of SAFV infection in which sulfated GAGs and integrin αVβ8 act through dual and cooperative pathways to facilitate viral entry.

DOI: https://doi.org/10.1038/s41467-025-67236-z
J Chromatogr A. 2025 Dec 03. pii: S0021-9673(25)00948-3. [Epub ahead of print]1766 466604

Quantitative profiling of aromatic amino acids and their host-microbial co-metabolites in human urine via UPLC-MS/MS.

Domniki Gallou, Olga Begou, Helen Gika, Vasiliki Sarli, Ian D Wilson, Georgios Theodoridis.

  The aromatic amino acids tryptophan, tyrosine and phenylalanine are involved in many biochemical pathways and their metabolism and co-metabolism by the human and the gut microbiota results in the production of a number of metabolites. Many of these are phenols which are excreted in the urine after either sulfation or glucuronidation by the host. These metabolic processes can be dysregulated due to factors such as inflammation, disease, dietary and/or pharmaceutical interventions. Validated, quantitative methods for the analysis of aromatic amino acids and their metabolites may therefore provide insights into host-gut microbiota symbiosis and its association with pathological conditions. As sulfation is often the favored form of conjugation for phenolic compounds, the development of analytical methods would benefit from access to the sulfate conjugates as reference standards, which unfortunately are scarce. To overcome this limitation nine sulfate conjugates were synthesized using standard chemical routes and were subsequently purified by preparative HPLC. Following structure confirmation (1H NMR and MS/MS analysis) the standards were used along with 24 other analytes for the development and validation of a quantitative LC-MS/MS-based assay. The method used a CSH Phenyl-Hexyl column to separate and analyze 33 aromatic amino acids and their metabolites in urine. The method was validated and subsequently applied to the analysis of urine obtained from 20 healthy individuals to obtain information on the relevant concentrations in human urine.

Keywords:  Aromatic amino acids; Chemical synthesis; Gut microbiota; LC-MS/MS; Method development; Sulfated metabolites

DOI:  https://doi.org/10.1016/j.chroma.2025.466604
Biochem Med (Zagreb). 2026 Feb 15. 36(1): 010705

Maternal serum steroid hormones in vaginal delivery and caesarean section.

Mirta Kadivnik, Dario Mandić, Jasenka Wagner, Kristina Kralik, Siniša Šijanović, Deni Plečko, Adrijana Muller, Gramos Begolli, Željko Debeljak.

   Introduction: The hormonal interplay between the mother and the fetal-placental unit may influence the mode of delivery. This study aimed to investigate the association between maternal peripartal serum concentrations of sex hormone-binding globulin (SHBG) and 10 steroid hormones with delivery outcomes.
Materials and methods: This observational study included 171 healthy pregnant women with spontaneous onset of labor: 117 had vaginal delivery and 54 underwent urgent cesarean section (C-section). Serum concentrations of aldosterone, androstenedione, cortisol, cortisone, corticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, progesterone, and total testosterone were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), while free testosterone was calculated. Sex hormone-binding globulin was measured by chemiluminescent microparticle immunoassay. Group differences were tested with the Mann-Whitney U test, and associations with delivery mode were assessed by logistic regression and receiver operating characteristic (ROC) analysis.
Results: Compared with the vaginal delivery group, women who underwent urgent C-section had significantly lower serum concentrations of SHBG, corticosterone, cortisol, aldosterone, progesterone, 17-hydroxyprogesterone, DHEA, DHEAS, and free testosterone (all P < 0.001). In multivariate logistic regression, aldosterone (odds ratio, OR 0.11, 95% CI 0.04 to 0.27, P < 0.001) and DHEAS (OR 0.74, 95% CI 0.58 to 0.94, P = 0.011) were independently associated with delivery mode. ROC analysis showed that aldosterone > 0.9 nmol/L predicted vaginal delivery with AUC 0.874, sensitivity 88%, and specificity 77%.
Conclusions: Low maternal aldosterone concentrations showed the strongest association with urgent C-section, suggesting that aldosterone may play a protective role in successful vaginal delivery.

Keywords:  aldosterone; cesarean section; delivery; steroids; vaginal

DOI:  https://doi.org/10.11613/BM.2026.010705
Acta Biomater. 2025 Dec 15. pii: S1742-7061(25)00934-1. [Epub ahead of print]

A sulfonated cartilage interpenetrating polymer network reinforces and protects the extracellular matrix of degraded cartilage.

Christian D DeMoya, Pierson Husted, Dev R Mehrotra, Michael B Albro, Brian D Snyder, Mark W Grinstaff.

  Cartilage extracellular matrix (ECM) comprises a type-II collagen fibril network that affords structure and tensile strength, complemented by a negatively charged, sulfated glycosaminoglycan (GAG) matrix that retains interstitial water. These components act synergistically, bestowing the rheological and tribological material properties essential to cartilage function. At the onset of osteoarthritis, a disease characterized by cartilage degeneration, GAGs diminish from the ECM reducing interstitial fluid load support (IFLS), equilibrium stiffness, and transferring load to the collagen fibril network, which subsequently breaks down, culminating in increased hydraulic permeability, and decreased cartilage stiffness. We restore the material properties of damaged cartilage critical to diarthrodial joint function by forming an interpenetrating polymer network (IPN) with the native collagen using a synthetic, hydrophilic, and biocompatible GAG-mimetic polymer. Upon visible light activation, the monomer, 3-sulfopropylmethacrylate (SPM), and the crosslinker, polyethylene glycol diacrylate (PEGDA), form a sulfonated and anionic IPN that fills the existing porous collagen matrix of degraded cartilage. Mechanistically, the highly sulfonated, anionic SPM IPN retards water transport, reestablishes collagen fibril network integrity, and restores tissue equilibrium stiffness, thereby returning the stiffness and viscoelastic properties of degraded cartilage to levels near healthy cartilage. Additionally, the SPM IPN protects cartilage reduces the infiltration of inflammatory cytokines that are known to upregulate catabolic matrix metalloproteinases and downregulate GAG production. STATEMENT OF SIGNIFICANCE: Amelioration of OA requires a comprehensive approach: neutralize or impede catabolic enzymes that degrade cartilage and reconstitute damaged cartilage by augmenting tissue ECM constituents. Currently, there are no clinical treatments that restore the viscoelastic material properties of hyaline cartilage tissue critical to its mechanical function and impart chondroprotection after OA induction. This work suggests that reconstituting GAG-depleted cartilage using a synthetic sulfonated interpenetrating polymer to reestablish IFLS instilled into the joint and polymerized with white light during conventional arthroscopy represents an effective, and minimally invasive strategy to restore the material properties of cartilage in the early stages of OA.

Keywords:  cartilage; extracellular matrix; interpenetrating polymer network; osteoarthritis,

DOI:  https://doi.org/10.1016/j.actbio.2025.12.028
Lipids. 2025 Dec 17.

A Novel Hypothesis for the Protective Rise in Cholesterol Sulfate Against Lipid Metabolic Disorders.

Xiaoyue Li, Chengcheng Wang, Yuming Wang, Tiantian Zhang.

  As a cholesterol metabolite, cholesterol sulfate (CS) is widely distributed in the human body, and its role as a regulatory factor has been continuously explored from the 1980s to the present day. However, changes in CS in metabolic disorders have not been systematically investigated. Here, rodent models of insulin resistance, fatty liver, and atherosclerosis were established. The CS content, CS to cholesterol ratio, and CS to total bile acids (TBA) ratio in the serum and liver of these model mice were compared with those of normal mice. Results showed the CS content was increased in fatty liver and atherosclerosis models of mice; meanwhile, it might be influenced by genotype, such as CD36 deficiency. The changes in the CS to cholesterol ratio were related to the amount and distribution of cholesterol. Besides, there was competition between the catabolism of cholesterol to bile acids or CS, as evidenced by the opposite trend between the TBA to cholesterol ratio and the CS to TBA ratio. Moreover, for the first time, it has been discovered that CS is enriched in lipid droplets, which further substantiates the close association between CS and lipid metabolism. Building on studies that demonstrated the beneficial effects of CS supplementation in alleviating lipid metabolic disorders, we first proposed the hypothesis that an increase in CS content may be protective against lipid metabolic disorders. This study provided a new perspective on the role of CS as a regulatory factor in metabolic disorders.

Keywords:  bile acids; cholesterol sulfate (CS); lipid droplets; metabolic disorders

DOI:  https://doi.org/10.1002/lipd.70031
J Anal Toxicol. 2025 Dec 19. pii: bkaf107. [Epub ahead of print]

Analysis of propranolol and its metabolites in postmortem human solid tissues and body fluids: LC-MS/MS approach with the standard addition method applied to a forensic case.

Mengchao Wang, Xiaoyu Zhou, Xiaolong Zhang, Yuxuan Chen, Jiajun Sun, Yaqin Sun, Jinlei Liu, Jie Gu, Amin Wurita, Hasegawa Koutaro.

   PURPOSE: This study aimed to develop a highly sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of propranolol and its metabolites in human biological samples. By analyzing their presence in urine, postmortem biological fluids, and various solid tissues, the study could be of reliable forensic toxicological use for investigations in propranolol poisoning cases. In this study, the Standard Addition Method (SAM) was used for quantification, and its validation was mixed with one of the analyte's concentrations.
METHODS: A 0.1 mL aliquot of each body fluid sample or 0.1 g each of homogenized solid tissue was mixed with one of the analyte concentration standards, extracted with methanol, spiked with an internal standard (IS) using the SAM, and purified using magnesium sulfate and sodium sulfate. Following centrifugation and filtration, samples were analyzed via LC-MS/MS. Urine samples underwent enzymatic hydrolysis with sulfatase and β-glucuronidase to measure conjugated metabolite forms prior to analysis.
RESULTS: Phase I metabolites (propranolol, 4-hydroxypropranolol, propranolol glycol, N-desisopropylpropranolol, 1-naphthylenyloxyacetic acid, and 1-naphthol) and phase II metabolites (sulfate and glucuronide conjugates) were identified in urine. Among postmortem samples, propranolol was highest in the bile, followed by the lung tissue. Naphthoxylactic acid could be consistently detected in all samples except for the brain, suggesting its potential as a good biomarker for propranolol exposure.
CONCLUSION: A validated LC-MS/MS method for determining propranolol and its metabolites in forensic samples was established, and it could also be applied to the authentic human samples obtained from a propranolol poisoning case. The findings could offer substantial and reliable support for investigating propranolol-related fatalities and contribute to the comprehensive understanding of the metabolism of propranolol in the human body.

Keywords:  Human biological samples; LC-MS/MS; Propranolol; metabolites

DOI:  https://doi.org/10.1093/jat/bkaf107
Handb Exp Pharmacol. 2025 Dec 16.

Comparison of the Biologic Activity of Different Species of Heparin.

Walter Jeske.

  Heparin and related low molecular weight heparin derivatives remain critical drugs for the prevention and treatment of thrombotic conditions. Concerns relating to the stability and sufficiency of the porcine intestinal mucosa supplies from which most heparin is currently derived have spurred an interest in identifying other sources for heparin. Commercial quantities of heparin may be obtained from cow and sheep intestine, and heparin or heparin-like material has been identified in a number of other species. Being biologic in nature, these heparins exhibit unique structural and functional profiles. This chapter summarizes our current understanding of these heparins.

Keywords:  Anticoagulant; Antithrombotic; Biologic; Bleeding; Heparin

DOI:  https://doi.org/10.1007/164_2025_781