bims-supasi 2025-05-04 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2025–05–04
fifteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Heparan-6-O-endosulfatase 2, a cancer-related proteoglycan enzyme, is effectively inhibited by a specific sea cucumber fucosylated glycosaminoglycan.
Chondroitin Sulfate E Regulates Neuronal Adhesion by Promoting Actin Polymerization Through Activation of the VEGF Receptor/Akt/GSK3β Pathway.
Ephrin-B1 regulates cell surface residency of heparan sulfate proteoglycans (HSPGs) and complexes with the HSPG CD44V3-10 and fibroblast growth factor receptors.
Structural insights and bioactivity of a cell wall sulfated polysaccharide from the marine diatom Cyclotella cryptica.
Amphiphilic Celecoxib-Polysaccharide Delivery System for Enhanced Colon-Targeted Colitis Therapy.
Co-therapy with S1P and heparan sulfate derivatives to restore endothelial glycocalyx and combat pro-atherosclerotic endothelial dysfunction.
Glycosaminoglycans: Mechanisms and therapeutic potential in neurological diseases: A mini-review.
Surrogate analyte approach for the determination of endogenous cortisol, cortisone, DHEA, DHEAS in horse hair and sheep wool by LC-HRMS/MS.
Substrate reduction using a glucosamine analogue in Drosophila melanogaster and mouse models of Sanfilippo syndrome.
Formation of low environment-sensitive whey protein isolate-dextran/chondroitin sulfate nanoparticles for cinnamaldehyde encapsulation and food preservation.
Redox-responsive chondroitin sulfate-based micelle system for enhanced chemotherapy and inflammation suppression to synergistically antitumor therapy.
The role of serum indoxyl sulfate and Klotho protein in cardiovascular complications among chronic kidney disease patients.
A New Method for the Quantification of Ethyl Sulfate and Isopropyl Sulfate Contents in Abacavir Sulfate by Ion Chromatography.
SnRK2s: Kinases or Substrates?
Dehydroepiandrosterone sulphate (DHEAS) supplementation impacts adrenal cortex morphophysiology of aged female gerbils.

Glycobiology. 2025 Apr 30. pii: cwaf025. [Epub ahead of print]

Heparan-6-O-endosulfatase 2, a cancer-related proteoglycan enzyme, is effectively inhibited by a specific sea cucumber fucosylated glycosaminoglycan.

Marwa Farrag, Reem Aljuhani, Julius Benicky, Hoda Al Ahmed, Sandeep K Misra, Sushil K Mishra, Joshua S Sharp, Robert J Doerksen, Radoslav Goldman, Vitor H Pomin.

  Heparan-6-O-endosulfatase 2 (Sulf-2) is a proteoglycan enzyme that modifies sulfation of heparan sulfate proteoglycans. Dysregulation of Sulf-2 is associated with various pathological conditions, including cancer, which makes Sulf-2 a potential therapeutic target. Despite the key pathophysiological roles of Sulf-2, inhibitors remain insufficiently developed. In previous work, a fucosylated chondroitin sulfate from the sea cucumber Holothuria floridana (HfFucCS) exhibited potent Sulf-2 inhibition. This study investigates the structural basis of HfFucCS-mediated Sulf-2 inhibition, examines the binding profile of HfFucCS to Sulf-2, and explores the mode of inhibition. Additionally, a structurally diverse library of sulfated poly/oligosaccharides, including common glycosaminoglycans and unique marine sulfated glycans, was screened for Sulf-2 inhibition. Results from a high-throughput arylsulfatase assay and specific 6-O-desulfation assay have proved that HfFucCS is the most potent among the tested sulfated glycans, likely due to the presence of the unique 3,4-disulfated fucose structural motif. HfFucCS demonstrated non-competitive inhibition, and inhibitory analysis of its low-molecular-weight fragments suggests a minimum length of ~7.5 kDa for effective inhibition. Surface plasmon resonance analyses revealed that Sulf-2 binds to surface heparin with high affinity (KD of 0.817 nM). HfFucCS and its derivatives effectively disrupt this interaction. Results from mass spectrometry-hydroxyl radical protein footprinting and repulsive scaling replica exchange molecular dynamics indicate similarities in the binding of heparin and HfFucCS oligosaccharides to both the catalytic and hydrophilic domains of Sulf-2. These findings reveal the unique inhibitory properties of a structurally distinct marine glycosaminoglycan, supporting its further investigation as a selective and effective inhibitor for Sulf-2-associated cancer events.

Keywords:  chondroitin sulfate; enzyme inhibitor; glycosaminoglycan; heparan-6-O-endosulfatase 2; proteoglycan

DOI:  https://doi.org/10.1093/glycob/cwaf025
Mol Neurobiol. 2025 Apr 28.

Chondroitin Sulfate E Regulates Neuronal Adhesion by Promoting Actin Polymerization Through Activation of the VEGF Receptor/Akt/GSK3β Pathway.

Naoki Sotogaku, Akinori Nishi.

  Neuronal adhesion is regulated by interactions between neurons and the extracellular matrix and plays a critical role in neural development. Chondroitin sulfate proteoglycans (CSPGs), key structural components of the extracellular matrix in the nervous system, are involved in various processes including neuronal migration, neurite outgrowth, and axonal regeneration. The diverse functions of CSPGs are controlled by the sulfated structures of chondroitin sulfate (CS) polysaccharides. In this study, we found that CS-E, a highly sulfated CS polysaccharide, but not CS-A, CS-B, CS-C, or CS -D, induced the formation of neuronal aggregates in primary cortical cells with features of immature neurons. This effect is likely due to the unique properties of CS-E, which altered cell adhesion to the coated surface of culture coverslips, leading to cell detachment and subsequent aggregate formation. Pharmacological and phosphorylation analyses aimed at elucidating signaling cascades revealed that the VEGF receptor is a cell surface target of CS-E, and subsequent activation of the Akt/GSK3β pathway plays a crucial role in aggregate formation. The c-Raf/GSK3β pathway is also involved in CS-E-induced aggregate formation. Furthermore, actin polymerization and the organization of the F-actin cytoskeleton, which are mediated through activation of the Akt/GSK3β pathway, were required for CS-E-induced aggregate formation. In summary, CS-E regulates neuronal adhesion by activating the VEGF receptor/Akt/GSK3β pathway. The identification of signaling cascades involving CS-E may provide insights into the mechanisms underlying neuronal development.

Keywords:  Actin polymerization; Akt; Chondroitin sulfate; Neuronal adhesion

DOI:  https://doi.org/10.1007/s12035-025-04946-x
Glycobiology. 2025 Apr 23. pii: cwaf020. [Epub ahead of print]35(6):

Ephrin-B1 regulates cell surface residency of heparan sulfate proteoglycans (HSPGs) and complexes with the HSPG CD44V3-10 and fibroblast growth factor receptors.

Kristian Prydz, Roger Simm, Erna Davydova, Hans-Christian Aasheim.

  The ephrin family of membrane proteins mediate intracellular signalling as ligands of transmembrane Eph tyrosine kinase receptors during cell-cell interactions. Ephrin/Eph signalling regulates processes like cell migration and angiogenesis and is of particular importance during embryonic development. Ephrins-A3 and -B3 can also bind to cell surface-associated and soluble heparan sulfate proteoglycans (HSPGs) that also play important roles during early development. Here we show that ephrins-B1, -B2, and -B3 all can bind in cis to cell surface HSPGs, while only ephrin-B1 interacts with cell surface HSPGs in a way that retards HSPG endocytosis. Expressing ephrin-B1 in HEK293T cells, using polyethyleneimine (PEI) as transfection agent, increased cell surface levels of HSPGs which were detected by an anti-heparan sulfate (HS) antibody or by ephrin-B3-Fc binding. Ephrin-B1 in the plasma membrane seemed to retard PEI-induced HSPG internalisation and degradation. Binding of HSPGs by ephrin-B1 was observed for the human, mouse, xenopus, and zebrafish homologs, and did not require the cytoplasmic tail of ephrin-B1 that contains tyrosines shown to be involved in intracellular signalling. Furthermore, ephrin-B1 could bind the HSPG variant of CD44 (CD44V3-10), a complex that could further associate with fibroblast growth factor receptors (1 and 4) after co-expression with one of these receptors. In summary, our data indicate that ephrin-B1 can regulate cellular HSPG turnover and is able to form complexes of potential biological importance with CD44V3-10 and fibroblast growth factor receptors.

Keywords:  CD44; Eph receptors; Ephrin-B1; FGF receptors; heparan sulfate proteoglycans

DOI:  https://doi.org/10.1093/glycob/cwaf020
Int J Biol Macromol. 2025 Apr 28. pii: S0141-8130(25)04163-7. [Epub ahead of print]311(Pt 1): 143611

Structural insights and bioactivity of a cell wall sulfated polysaccharide from the marine diatom Cyclotella cryptica.

Serena Leone, Rosa Giugliano, Camilla Borgonuovo, Fabrizio Chiodo, Antonio Molinaro, Carla Zannella, Anna De Filippis, Massimiliano Galdiero, Yvette van Kooyk, Stefania De Chiara, Chiara Magnabosco, Flaviana Di Lorenzo, Giovanna Romano.

  Sulfated Polysaccharides (SPs) are abundant in marine organisms, where they play an essential role in the mechanisms of adaptation to saline environments. SPs from macro- and microalgae possess unique structural features, which often correlate to taxonomy, and are under active investigation due to their various potential fields of application. We have investigated the structure of the sulfated polysaccharide isolated from the cell wall of the marine diatom Cyclotella cryptica (CcSP), finding that it consisted of a homopolysaccharide with a backbone of (1 → 4)-⍺-d-Manp carrying, in the most abundant form, sulfation at O-6. CcSP exhibited promising antiviral activity against Herpes Simplex Virus-1 (HSV-1), which was likely associated with a mechanism involving steric hindrance and/or electrostatic repulsion, preventing viral attachment to host cells. In addition, we have also proved the binding of CcSP to the innate human receptor Langerin, a well-known C-type lectin that recognizes sulfated polysaccharides and is involved in virus entry in cells. We attempted to partially reconstruct the biosynthetic pathway of CcSP: analysis of C. cryptica genome revealed the presence of several putative carbohydrate 6-O sulfotransferases (CH-STs) with homology to the human enzymes involved in glycosaminoglycans sulfation. Our results suggest an ancient evolutionary origin for the regioselective specialization of CH-STs, and could pave the way for future research on diatom cell wall biogenesis, as well as for biotechnological applications relying on the manipulation of the sulfation levels in CcSP for enhanced activity.

Keywords:  Antiviral activity; Carbohydrate sulfotransferase; Cyclotella cryptica; Diatoms; Sulfated polysaccharides

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143611
Pharmaceutics. 2025 Apr 12. pii: 511. [Epub ahead of print]17(4):

Amphiphilic Celecoxib-Polysaccharide Delivery System for Enhanced Colon-Targeted Colitis Therapy.

Qiao Qiao, Xian Wan, Jie Li, Weijun Chen, Enxuan Li, Lipeng Qiu, Huiming Tu.

  Background: Ulcerative colitis (UC), a subtype of chronic inflammatory bowel disease (IBD), is primarily treated with oral medications to reduce inflammation and alleviate symptoms. Celecoxib (CXB) is an attractive candidate for UC; however, its limited solubility and low bioavailability pose significant challenges to its clinical application. Methods: We reported a novel chondroitin sulfate A-Celecoxib (CSA-CXB) polymeric nanoprodrug to address the limited solubility and low bioavailability of CXB. CXB was conjugated to chondroitin sulfate A (CSA) via succinic anhydride (SA) and ethylenediamine to prepare CSA-CXB polymers, which can self-assemble into nanoparticle structural prodrugs in aqueous condition. We investigated the stability, blood compatibility, and responsiveness of the nanoparticles. The ability of the nanoparticles to treat UC in vitro and in vivo was then evaluated. Results: The CSA-CXB nanoprodrug was spherical with a mean particle size of 188.4 ± 2.2 nm, a zeta potential of -22.9 ± 0.1 mV, and sustained drug release behavior. Furthermore, CSA-CXB exhibited remarkable antioxidant and anti-inflammatory effects, as it can significantly increase the free radical scavenging rate and reduce the expression level of ROS, TNF-α, IL-6, nitric oxide (NO), and COX-2 protein in vitro. In vivo results demonstrated that CSA-CXB targeted the mice's colon efficiently mitigate UC symptoms by inhibiting the expression of inflammatory cytokine. Conclusions: The CSA-CXB nanoprodrug can improve the therapeutic impact of CXB, and has potential as a new preparation for a clinical UC treatment nanoprodrug.

Keywords:  celecoxib; chondroitin sulfate; drug delivery; ulcerative colitis

DOI:  https://doi.org/10.3390/pharmaceutics17040511
Life Sci. 2025 Apr 23. pii: S0024-3205(25)00297-8. [Epub ahead of print] 123662

Co-therapy with S1P and heparan sulfate derivatives to restore endothelial glycocalyx and combat pro-atherosclerotic endothelial dysfunction.

Ronodeep Mitra, Kaleigh Pentland, Svilen Kolev, Matthew Eden, Erel Levine, Jessica M Oakes, Eno E Ebong.

   AIMS: Endothelial cell (EC) glycocalyx (GCX) shedding from disturbed blood flow and chemical factors leads to low-density lipoprotein infiltration, reduced nitric oxide synthesis, vascular dysfunction and atherosclerosis. This study evaluates a therapy combining sphingosine-1-phosphate (S1P) and heparin (heparan sulfate derivative). We hypothesized that heparin/S1P co-treatment repairs mechanically damaged EC GCX in disturbed flow (DF) regions and restores anti-atherosclerotic mechanotransduction to treat cardiovascular disease.
MATERIALS AND METHODS: We used a parallel-plate flow chamber to simulate flow conditions in vitro and a partial carotid ligation mouse model to mimic DF in vivo. Heparin and albumin-bound S1P were administered to assess their reparative effects on the endothelial GCX. Fluorescent staining, confocal microscopy, and ultrasound evaluated endothelial cell function and endothelial-dependent vascular function. Barrier functionality was assessed via macrophage uptake. Heparin/S1P mechanism-of-action insights were gained through fluid dynamics simulations and staining of GCX synthesis enzyme and S1P receptor. Statistical analyses validated the results.
KEY FINDINGS: The in vitro data showed that heparin/S1P therapy improves DF-conditioned ECs by restoring GCX and elevating vasodilator eNOS (endothelial-type nitric oxide synthase) expression. In vivo studies confirmed GCX degradation, vessel inflammation, hyperpermeability, and wall thickening in the mouse model's partially ligated left carotid artery. Heparin/S1P treatment restored GCX thickness and coverage, reduced inflammation and hyperpermeability, and inhibited vessel wall thickening.
SIGNIFICANCE: This work introduces a new approach to regenerating the EC GCX and restoring its function in ECs under DF conditions, offering a groundbreaking solution for preventing cardiovascular diseases like atherosclerosis.

Keywords:  Cardiovascular disease treatment; Endothelial dysfunction; Endothelial glycocalyx; Glycocalyx regeneration; Heparin; Sphingosine-1-phosphate

DOI:  https://doi.org/10.1016/j.lfs.2025.123662
Biochem Biophys Res Commun. 2025 Jun 08. pii: S0006-291X(25)00575-3. [Epub ahead of print]765 151861

Glycosaminoglycans: Mechanisms and therapeutic potential in neurological diseases: A mini-review.

Tahir Ali, Iram Murtaza, Hongling Guo, Shupeng Li.

  Glycosaminoglycans (GAGs) are vital polysaccharides that constitute key elements of the extracellular matrix (ECM), particularly within chondroitin sulfate proteoglycans (CSPGs). GAGs exhibit a dual role in neural tissue: they facilitate synaptic plasticity and cellular adhesion, essential for neural function, while posing as barriers to axonal regeneration following injury. Through interactions with diverse proteins, including enzymes, cytokines, and growth factors, GAGs critically influence neural development, repair, and homeostasis. Recent advancements have underscored the therapeutic potential of modulating GAG synthesis, degradation, and receptor interactions to address neuroinflammation, promote neural repair, and counteract inhibitory signals in the injured CNS. Furthermore, combining GAG-targeted therapies with complementary approaches, such as gene therapy or nanoparticle-based delivery systems, holds promise for achieving synergistic effects and enhancing treatment outcomes. This mini-review explores the multifaceted roles of GAGs in neural physiology and pathology, highlighting their emerging potential as therapeutic targets for neurological disorders.

Keywords:  CSPG; ECM; GAG; Neurological diseases

DOI:  https://doi.org/10.1016/j.bbrc.2025.151861
Sci Rep. 2025 Apr 29. 15(1): 14987

Surrogate analyte approach for the determination of endogenous cortisol, cortisone, DHEA, DHEAS in horse hair and sheep wool by LC-HRMS/MS.

Federica Castellani, Matteo Ricci, Roberta Rosato, Alessia Manucci, Vanessa Di Simone, Francesco Cerasoli, Amelia Calandrini, Emanuela Dalla Costa, Michele Podaliri Vulpiani, Giampiero Scortichini, Giorgio Saluti.

Two new quantitative methods for the determination of four stress-related hormones (cortisol, cortisone, dehydroepiandrosterone and dehydroepiandrosterone sulfate) in horse hair and sheep wool by liquid chromatography coupled with hybrid high resolution mass spectrometry were developed and validated. Hormones were extracted overnight from ground samples with methanol after a washing step with the same solvent to remove external contamination. The extract was evaporated and dry residue was solubilized in an acid mixture of methanol and water. The methods were validated according to ICH guidelines for bioanalytical method validation within 5-100 pg/mg with LC-Q Exactive platform (except for DHEA: 100-2000 pg/mg for both matrices and 1-100 pg/mg for DHEAS in mane hair). The validated concentration range was 5-100 pg/mg for wool and 1-100 pg/mg (except for DHEA: 5-100 pg/mg) for mane hair samples with LC-Exploris 120 system. Satisfactory quantitative performances were obtained using isotopic dilution and surrogate analyte approach. After successful validation, the applicability of the methods were tested. The detected concentrations of investigated analytes in real samples collected from animals living in marginal areas were encompassing the interval 1.1-13 and 5.0-30.5 pg/mg in mane hair and wool samples, respectively.

DOI: https://doi.org/10.1038/s41598-025-99470-2
Mol Genet Metab. 2025 Apr 19. pii: S1096-7192(25)00103-9. [Epub ahead of print]145(2): 109112

Substrate reduction using a glucosamine analogue in Drosophila melanogaster and mouse models of Sanfilippo syndrome.

Sher Li Tan, Daniel Neumann, Paul J Trim, Laura J Hewson, Nooramirah Farhana Mustaffar, Qi Qi He, Norbert Wimmer, Marten F Snel, Vito Ferro, Louise V O'Keefe, Kim M Hemsley, Adeline A Lau.

  Mucopolysaccharidosis (MPS) types III A and C are inherited neurodegenerative disorders resulting from the lack of a specific enzyme involved in heparan sulfate (HS) catabolism, leading to the accumulation of partially-degraded HS fragments. At present, there are no approved treatments and death is commonly in the second decade of life. Several therapies have undergone pre-clinical evaluation for these conditions, including substrate reduction therapy, with the most studied compound of this class being the isoflavone genistein. However, findings from a Phase III clinical trial demonstrated that high dose oral genistein did not significantly improve neurodevelopmental outcomes in patients with MPS III (Sanfilippo syndrome). Here, we have tested an N-acetylglucosamine analogue, 4-deoxy-N-acetylglucosamine peracetate, as a novel substrate reduction therapy for HS-storing lysosomal storage disorders such as MPS III. Treatment with this compound significantly reduced HS levels in cultured MPS IIIA patient and mouse fibroblasts in a time- and dose-dependent manner. MPS IIIC Drosophila fed 4-deoxy-N-acetylglucosamine peracetate contained significantly less HS relative to those raised on control diets. Likewise, improvements in HS load within the MPS IIIA mouse brain suggests that the compound crossed the blood-brain barrier after oral administration. Although long-term studies are needed, these findings indicate that 4-deoxy-GlcNAc peracetate may be beneficial in slowing the accumulation of HS and may represent a novel substrate reduction therapeutic for MPS III and potentially other HS-storing disorders.

Keywords:  Drosophila; Heparan sulfate; Mouse; Mucopolysaccharidosis; Sanfilippo; Substrate reduction therapy

DOI:  https://doi.org/10.1016/j.ymgme.2025.109112
Int J Biol Macromol. 2025 Apr 30. pii: S0141-8130(25)04226-6. [Epub ahead of print] 143674

Formation of low environment-sensitive whey protein isolate-dextran/chondroitin sulfate nanoparticles for cinnamaldehyde encapsulation and food preservation.

Qian Liu, Bertrand Muhoza, Shiqing Song, Xiaoming Zhang.

  Cinnamaldehyde is regarded as a secure antibacterial agent for various food matrices, but the volatility and insolubility restrict its application. Biopolymer nanoencapsulation was emerging as an effective tool to address these drawbacks. However, current nanoparticle fabrication methods enabled cinnamaldehyde protection and sustained release only under narrow pH ranges and low ionic strength, failing to provide simultaneous compatibility with the diverse pH and ionic strength variations encountered in complex food systems. Herein, whey protein isolates-dextran/ chondroitin sulfate (WPI-dextran/ChS) nanoparticles applicable to most of the food systems with varied pH (1-10) and salt level (0-2 mol/L) were obtained based on Maillard reaction and heat-induced gelation. Dynamic light scattering, encapsulation efficiency and loading capacity indicated that the nanoparticles prepared from WPI-dextran conjugates with 3-day incubation exhibited relatively better dispersity and loading ability for cinnamaldehyde. Better antioxidant and antibacterial ability were also observed, with DPPH and ABTS radical scavenging rates of 55.08 % and 47.42 %, lipid peroxidation inhibiting activity of 48.24 %, and the antibacterial efficiency of 83 % and 89 % against E. coli and S. aureus, respectively. The excellent performance of cinnamaldehyde-loaded nanoparticles in preservation of sauced pork was corroborated by multiparametric analysis, which showed that the deterioration of sauced pork was significantly retarded.

Keywords:  Antibacterial activity; Antioxidant ability; Cinnamaldehyde; Food preservation; Low environment-sensitive nanoparticle; Maillard conjugation

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143674
Int J Biol Macromol. 2025 Apr 29. pii: S0141-8130(25)04238-2. [Epub ahead of print] 143686

Redox-responsive chondroitin sulfate-based micelle system for enhanced chemotherapy and inflammation suppression to synergistically antitumor therapy.

Miaomiao Long, Weijun Chen, Jie Li, Weibo Kong, Min Su, Lipeng Qiu, Xian Cheng, Liangwu Bi.

  According to the close association between cancer and inflammation demonstrated in clinical data, the strategy of synergistic anti-tumor and anti-inflammatory therapy shows promising potential. However, challenges remain in the synthesis and development of co-delivery systems for synergistic therapy. Herein, an amphiphilic chondroitin sulfate-rosmarinic acid polymeric prodrug was synthesized, and then combined with DSPE-PEG to encapsulate doxorubicin, forming a redox-responsive nanomicelle (PRSC/DOX) delivery system. PRSC/DOX exhibited a particle size of 188.6 nm and remained stable in PBS for at least 7 days. PRSC/DOX was internalized into tumor cells via CD44 receptor-mediated endocytosis, and degraded by intracellular glutathione to release the drugs. The released doxorubicin killed tumor cells through chemotherapy, and rosmarinic acid inhibited tumor cell growth by suppressing inflammation levels in the tumor microenvironment. In vivo experiments showed a statistically significant decrease in the inflammation levels in mice, along with a considerable reduction in tumor volume. Consequently, the PRSC/DOX significantly enhanced antitumor efficacy through a synergistic therapy of chemotherapy and inflammation suppression.

Keywords:  Chondroitin sulfate; Doxorubicin; Micelles; Rosmarinic acid; Synergistic therapy

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143686
Int J Artif Organs. 2025 May 01. 3913988251334878

The role of serum indoxyl sulfate and Klotho protein in cardiovascular complications among chronic kidney disease patients.

Qiang Liu, Qian Wang, Weina Zhang, Tiantian Jin, Beining Wang, Jie Liang, Ye Li, Si Zhang, Li Zhang, Yan Gao.

   OBJECTIVE: This study aimed to investigate the relationship between the changes of serum indoxyl sulfate (IS) concentration, Klotho protein level, and cardiovascular complications in patients with chronic kidney disease (CKD) stage 3-5.
METHODS: A total of 108 patients with CKD stage 3-5 were selected. They were divided into three groups: CKD stage 3-4 group, CKD stage 5 non-dialysis group, and CKD stage 5 dialysis group. Echocardiography was used to measure left ventricular diameter (LVD), interventricular septal thickness (IVS), left ventricular posterior wall thickness (LVPW), and calcification.
RESULTS: there was no significant difference in age between the healthy control group and the patients with CKD stage 3-5 (p > 0.05). Compared to healthy controls, serum creatinine, serum phosphorus, iPTH, serum IS, left ventricular diameter, interventricular septum thickness, left ventricular septal wall thickness, and the proportion of valve calcification increased gradually, while serum calcium and Klotho protein decreased The level of serum IS was positively correlated with the level of LVD, IVS, and valve calcification in CKD patients, while the level of serum Klotho protein was negatively correlated with the level of IVS and valve calcification in CKD patients.
CONCLUSION: In patients with chronic kidney disease (CKD), the incidence of cardiovascular complications is significantly higher than in the general population. The increase of serum IS level and the decrease of serum Klotho protein level are closely related to cardiac injury, it IS suggested that serum IS level and Klotho protein level may be a good index for monitoring cardiovascular injury in CKD patients.

Keywords:  Chronic kidney disease; Klotho; cardiac injury; indoxyl sulfate

DOI:  https://doi.org/10.1177/03913988251334878
J Chromatogr Sci. 2025 Mar 27. pii: bmaf023. [Epub ahead of print]63(4):

A New Method for the Quantification of Ethyl Sulfate and Isopropyl Sulfate Contents in Abacavir Sulfate by Ion Chromatography.

Venkata Ramana Reddy Junuthula, Surendra Babu Manabolu Surya, Naresh Kumar Katari, Chandrasekhar Reddy Kandati, Narendra Kumar Masani, Hemant Kumar Sharma.

A predictable new method was developed and validated for the determination of ethyl sulfate (EtS) and isopropyl sulfate (IprS) contents in abacavir sulfate (ABS) drug substance by ion chromatography (IC). Ethyl alcohol, isopropyl alcohol and sulfuric acids were used in the manufacturing process of ABS. Therefore, there is a possibility to form respective sulfate impurities, i.e., EtSs and IprSs. Hence, a control strategy is required for EtS and IprS contents in ABS. Chromatographic separation of EtS and IprS contents in Abacavir sulfate was achieved on Metrosep A Supp 10 (250 mm × 4.0 mm) column and particles of 4.6 μm size. The mobile phase consists of buffer (3.2 mM Sodium carbonate and 1.0 mM of sodium bicarbonate) and acetonitrile in the ratio of 90:10 (v/v) with the flow rate of 0.6 mL min-1 by applying 30°C column oven temperature. The analytes were monitored by conductometric detector. The performance of the method was assessed by evaluating the specificity, linearity, sensitivity, precision, robustness and accuracy experiments. The limit of detection and limit of quantification values for EtS were 0.3 and 0.8 μg mL-1 and for IprS were 0.3 and 0.8 μg mL-1, respectively. The correlation co-efficient value of linearity experiment was 0.9999 for EtS, 0.9998 for IprS. The average recovery for EtS was 98.7% and for IprS was 100.9%. The method is robust for EtS and IprS contents and also specific from other common anions, i.e., chloride, bromide, nitrate, sulfate, methyl sulfate and methanesulfonic acids. The results proved that the validated method was simple and cost-effective for controlling EtS and IprS contents in ABS drug substance, and the method can be successfully applied in the quality control analysis.

DOI: https://doi.org/10.1093/chromsci/bmaf023
Plants (Basel). 2025 Apr 09. pii: 1171. [Epub ahead of print]14(8):

SnRK2s: Kinases or Substrates?

Yunmin Wei, Linzhu Peng, Xiangui Zhou.

  Throughout their life cycle, plants persistent through environmental adversities that activate sophisticated stress-signaling networks, with protein kinases serving as pivotal regulators of these responses. The sucrose non-fermenting-1-related protein kinase 2 (SnRK2), a plant-specific serine/threonine kinase, orchestrates stress adaptation by phosphorylating downstream targets to modulate gene expression and physiological adjustments. While SnRK2 substrates have been extensively identified, the existing literature lacks a systematic classification of these components and their functional implications. This review synthesizes recent advances in characterizing SnRK2-phosphorylated substrates in Arabidopsis thaliana, providing a mechanistic framework for their roles in stress signaling and developmental regulation. Furthermore, we explore the understudied paradigm of SnRK2 undergoing multilayered post-translational modifications (PTMs), including phosphorylation, ubiquitination, SUMOylation, S-nitrosylation, sulfation (S-sulfination and tyrosine sulfation), and N-glycosylation. These PTMs collectively fine-tune SnRK2 stability, activity, and subcellular dynamics, revealing an intricate feedback system that balances kinase activation and attenuation. By integrating substrate networks with regulatory modifications, this work highlights SnRK2's dual role as both a phosphorylation executor and a PTM-regulated scaffold, offering new perspectives for engineering stress-resilient crops through targeted manipulation of SnRK2 signaling modules.

Keywords:  SnRK2; phosphorylation; post-translational modification; substrates

DOI:  https://doi.org/10.3390/plants14081171
Steroids. 2025 Apr 23. pii: S0039-128X(25)00059-5. [Epub ahead of print] 109618

Dehydroepiandrosterone sulphate (DHEAS) supplementation impacts adrenal cortex morphophysiology of aged female gerbils.

Carolina Marques Bedolo, Isabella Carolina Cozim, Vitor Grigio, Gabriel Ribeiro Bernussi, Stella Bicalho Silva, Luiz Henrique Alves Guerra, Silvana Gisele Pegorin de Campos, Patrícia Simone Leite Vilamaior, Ellen Cristina Rivas Leonel, Sebastião Roberto Taboga.

  During the process of aging, it is common for women to take dehydroepiandrosterone sulphate (DHEAS) supplements to prevent adrenopause. However, the potential effects of this supplementation on the adrenal cortex have not yet been fully elucidated. Therefore, the present study aimed to analyze the effects of DHEAS supplementation on the adrenal cortex of female Mongolian gerbils during the aging process. The experiment was conducted by dividing the aged female gerbils (18 months of age) into two groups (n = 5). The control group received no treatment, while the experimental group received 60 mg/kg of DHEAS for 5 weeks. The adrenal glands of both groups were then subjected to morphological, hormonal and immunohistochemistry analyses. The results showed that DHEAS supplementation led to a significant increase in the accumulation of lipofuscin granules in the adrenal cells. Furthermore, decreases in ERα and ERβ and the enzymes CYP17 and 17βHSD, and an increase in the 5α-reductase enzyme in the adrenal cortex were also observed. The results suggest that DHEAS supplementation has a negative feedback effect on the adrenal cortex, affecting its morphophysiology and, consequently, the gland's functionality. In addition, DHEAS supplementation does not reverse all aspects of the effects of aging on adrenal gland homeostasis.

Keywords:  Adrenopause; Androgens; Female adrenal; Hormone; Steroidogenesis; Supplementation

DOI:  https://doi.org/10.1016/j.steroids.2025.109618