bims-supasi 2025-07-27 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2025–07–27
fifteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

The Role of Heparan Sulfate in Bone Repair and Regeneration.
Sulfated polysaccharide from Phyllophorella kohkutiensis: Extraction, purification, and bioactivity assessment.
Shear Stress-Dependent Modulation of Endothelin B Receptor: The Role of Endothelial Glycocalyx Heparan Sulfate.
Visual Ratiometric Fluorescent Capsule for Ultralow Detection of Indoxyl Sulfate: A Paradigm Shift in Point-of-Care Chronic Kidney Disease Diagnostics.
A Novel Sprayable Fibrinogen/Glycosaminoglycans/Collagen-Based Bioink for Skin Wound Healing Applied by a Handheld Dual-Head Airbrush.
Development of an ophthalmic solution combining allogenic plasma with protective excipients for enhanced therapeutic role in the management of ocular surface diseases.
Brassinosteroid signaling promotes sulfate uptake under sulfur deficiency in Arabidopsis.
Sulfation and carboxymethylation of Citrus medica 'Fingered' polysaccharides: Physicochemical properties and protective effects against LPS-induced intestinal barrier injury in Caco-2 cells.
The GTE7-IES2B-GTE2 complex epigenetically regulates sulfur homeostasis in Arabidopsis thaliana.
Enhanced diagnostic potential of CSPG4 in melanoma and nevi: a comparative study with PRAME, CDC7 and Ki67.
Raider of the lost N-glycans - Localizing rare and frequently overlooked IgG N-glycans with sulfation or bisecting LacNAc.
Bioactive Polysulfate-Based Nano-Assemblies Against Virus Infection.
Cladolosides of Groups S and T: Triterpene Glycosides from the Sea Cucumber Cladolabes schmeltzii with Unique Sulfation; Human Breast Cancer Cytotoxicity and QSAR.
Associations Between Uraemic Toxins and Gut Microbiota in Adults Initiating Peritoneal Dialysis.
The influence of gut microbiota on the gut-brain-kidney axis and its implications for chronic kidney disease.

Calcif Tissue Int. 2025 Jul 24. 116(1): 102

The Role of Heparan Sulfate in Bone Repair and Regeneration.

Yuehua Li, Lei Zheng, Wenjie Cheng, Bozhi Hou, Raymond Chung Wen Wong.

  Heparan sulfate (HS) is synthesized in majority of cells in the human body and is typically released as an extension of polysaccharide chains, which then covalently bind to the protein core of proteoglycans to form heparan sulfate proteoglycans (HSPG). Research has shown that HS plays a crucial role in various cellular pathways of bone repair and regeneration and this review aims to summarize the role of HS in the above process. We found that the specific role of HS in bone repair and regeneration may depend on its location by analyzing the published research. Compared to cell surface HS, research on extracellular matrix (ECM) HS is limited. The current research suggests that HS can prevent the formation of blood clots after bone fracture and has a dual role in inflammation. ECM HS promotes soft callus formation and mineralization, while cell surface HS has inhibitory effects.

Keywords:  Bone deficiency; Bone repair and regeneration; Bone tissue engineering; Heparan sulfate; Heparan sulfate proteoglycan

DOI:  https://doi.org/10.1007/s00223-025-01413-6
Food Chem X. 2025 Jul;29 102772

Sulfated polysaccharide from Phyllophorella kohkutiensis: Extraction, purification, and bioactivity assessment.

Pornpun Aramsangtienchai, Thanchanok Sirirak, Patchaporn Seesan, Wirunyupha Singrakphon, Jongkonnee Padungkasem, Klaokwan Srisook, Janjarus Watanachote.

  Sulfated polysaccharides from marine sources exhibit diverse biological activities influenced by species and extraction methods. Herein, a sulfated polysaccharide (Pk-P1) was isolated and purified from the edible sea cucumber Phyllophorella kohkutiensis Heding & Panning, 1954. Structural characterization revealed that Pk-P1 is primarily composed of chondroitin sulfate. Thermogravimetric analysis demonstrated its thermal stability up to 231 °C, supporting its suitability for food processing applications. Both crude and purified polysaccharides significantly inhibited nitric oxide production in LPS-induced RAW264.7 macrophages, with IC50 values of 128.90 ± 12.03 and 105.12 ± 16.57 μg/mL, respectively, without cytotoxicity at tested concentrations. Antioxidant assays also confirmed their free radical scavenging activity and ferric-reducing power. These results highlight the dual anti-inflammatory and antioxidant properties of Pk-P1, supporting its potential as a functional food ingredient or nutraceutical. This work underscores the value of marine-derived sulfated polysaccharides for promoting health and reducing oxidative stress.

Keywords:  Anti-inflammation; Antioxidant; Heding & Panning, 1954; Marine resources; Phyllophorella kohkutiensis; Sulfated polysaccharide

DOI:  https://doi.org/10.1016/j.fochx.2025.102772
Cells. 2025 Jul 16. pii: 1088. [Epub ahead of print]14(14):

Shear Stress-Dependent Modulation of Endothelin B Receptor: The Role of Endothelial Glycocalyx Heparan Sulfate.

Camden Holm, Son Nam Nguyen, Solomon A Mensah.

  The endothelial glycocalyx (GCX) plays a crucial role in vascular health and integrity and influences many biochemical activities through mechanotransduction, in which heparan sulfate (HS) plays a major role. Endothelin-1 (ET-1) is a potent vasoregulator that binds to the endothelin B receptor (ETB) on endothelial cells (ECs), stimulating vasodilation, and to the endothelin A receptor on smooth muscle cells, stimulating vasoconstriction. While the shear stress (SS) dependence of ET-1 and HS is well documented, there is limited research documenting the SS dependence of the ETB. Understanding the SS dependence of the ETB is crucial for clarifying the role of hemodynamic forces in the endothelin system. We hypothesize that GCX HS regulates the expression of the ETB on the EC surface in an SS-dependent manner. Human lung microvascular ECs were exposed to SS in a parallel-plate flow chamber for 12 h. Damage to the GCX was simulated by treatment with 15 mU/mL heparinase-III during SS exposure. Immunostaining and qPCR were used to evaluate changes in ET-1, ETB, and HS expression. Results indicate that ETB expression is SS sensitive, with at least a 1.3-fold increase in ETB protein expression and a 0.6 to 0.4-fold-change decrease in ETB mRNA expression under SS. This discrepancy suggests post-translational regulation. In some cases, enzymatic degradation of HS attenuated the SS-induced increase in ETB protein, reducing the fold-change difference to 1.1 relative to static controls. This implies that ETB expression may be partially dependent on HS-mediated mechanotransduction, though inconclusively. Furthermore, ET-1 mRNA levels were elevated two-fold under SS without a corresponding rise in ET-1 protein expression or significant impact from HS degradation, implying that post-translational regulation of ET-1 occurs independently of HS.

Keywords:  endothelial glycocalyx; endothelin B receptor; endothelin-1; heparan sulfate; mechanotransduction; shear stress; vascular disease

DOI:  https://doi.org/10.3390/cells14141088
ACS Appl Mater Interfaces. 2025 Jul 22.

Visual Ratiometric Fluorescent Capsule for Ultralow Detection of Indoxyl Sulfate: A Paradigm Shift in Point-of-Care Chronic Kidney Disease Diagnostics.

Lian Xiao, Hu Di, Zhang Ruilong, Niu Helin.

  Indoxyl sulfate (IS), a protein-bound uremic toxin implicated in chronic kidney disease (CKD) progression and extrarenal pathologies, necessitates the development of accessible monitoring tools for point-of-care diagnostics. To address this challenge, we engineered a portable fluorescent capsule device by encapsulating an antenna-effect-enhanced europium metal-organic gel (EuMOG) within a biocompatible alginate matrix. This innovative sensor exhibits specific ratiometric fluorescence modulation toward IS via a photoinduced electron transfer (PET) mechanism, wherein IS binding triggers a distinct emission shift: quenching of Eu3+ red emission (619 nm) with concurrent 29-fold enhancement of ligand-centered blue emission (393 nm). Significantly, the capsule achieves ultrasensitive detection with record-low detection limits of 1.9 ppb in urine and 43.61 ppm in serum─surpassing conventional methods by orders of magnitude─while maintaining selectivity against structurally similar metabolites (e.g., uric acid, creatinine) and physiological interferents in complex matrices. The visually discernible pink-to-blue transition under UV light enables instrument-free, real-time semiquantification within 16 min, as validated by linear ratiometric responses across clinically relevant IS concentrations (1-900 μM, R2 = 0.996). The integration of room-temperature synthesis, dynamic capsule dissolution kinetics, and PET-driven specificity establishes a paradigm shift toward deployable CKD diagnostics, particularly for resource-limited settings.

Keywords:  indoxyl sulfate monitoring; lanthanide luminescent gel; metal−organic gels; point-of-care diagnostics; ratiometric fluorescence

DOI:  https://doi.org/10.1021/acsami.5c11830
Adv Healthc Mater. 2025 Jul 25. e00702

A Novel Sprayable Fibrinogen/Glycosaminoglycans/Collagen-Based Bioink for Skin Wound Healing Applied by a Handheld Dual-Head Airbrush.

Paula Pleguezuelos-Beltrán, Daniel Nieto-García, Carlos Chocarro-Wrona, Juan de Vicente, Patricia Gálvez-Martín, José Manuel Entrena, Elena López-Ruiz, Juan Antonio Marchal.

  In the last years, different biofabrication methods have gained special attention for the production of skin substitutes that overcome the limitations of conventional skin grafting. Skin sprays represent a promising technology for treating cutaneous wounds as they can deliver both cells and biomaterials to the wound bed in a fast and easy approach, covering extensive wound surfaces. The aim of this study is to develop a novel bioink based on fibrinogen supplemented with a glycosaminoglycans (GAGs)/collagen (Col)-based matrix, containing hyaluronic acid, dermatan sulfate, chondroitin sulfate, and Col, in combination with an innovative dual-head airbrush-based spraying device. The fibrinogen/GAGs/Col-based bioink is loaded with human mesenchymal stromal cells or human dermal fibroblasts, and its physicochemical and mechanical properties are analyzed, as well as cell viability, metabolic activity, and in vitro wound healing. Finally, its skin wound healing properties are studied in an in vivo excisional wound healing murine model. The bioink forms hydrogels with satisfactory physicochemical, mechanical, and biological properties, capable of promoting wound healing and tissue regeneration in vivo with outcomes comparable to those of autografts. The novel spray system and bioink show the potential to serve as a therapeutic tool for the clinical treatment of cutaneous wounds.

Keywords:  biofabrication; bioinks; fibrin; skin; sprays

DOI:  https://doi.org/10.1002/adhm.202500702
Eur J Pharm Biopharm. 2025 Jul 20. pii: S0939-6411(25)00190-0. [Epub ahead of print] 114813

Development of an ophthalmic solution combining allogenic plasma with protective excipients for enhanced therapeutic role in the management of ocular surface diseases.

Agnès Roche, Philip Chennell, Frédéric Chiambaretta, Anne Françoise Serre-Sapin, Mathieu Wasiak, Yassine Bouattour, Valentin Bailly-De-France, Anne Fogli, Julie Durif, Régine Quinard, Mireille Jouannet, Vincent Sapin, Valérie Sautou.

  Ocular surface diseases (OSDs) are characterised by an instability of the tear film. In severe cases, these disorders have been improved by using human serum or plasma formulated into eye drops. These blood-derived-products present a biological composition similar to that of tears and contain beneficial factors that modulate inflammation and tissue regeneration. However, the supply of blood derivatives remains a challenge due to the potential microbiological risk, the quality and inter-individual heterogeneity of the biological samples used, and logistical difficulties. Thus, the idea behind this work was to use a standardised blood-derived product produced and checked industrially from a pool of donors, and to combine it with protective excipients known for their lubricating, anti-inflammatory, and regenerative properties offering new treatment opportunities for OSDs. Attention was also given to the non-bioaccumulative nature of the excipients. In order to select the concentrations of different compounds of interest in the ophthalmic solution, a design of experiment was used to establish a formulation with physicochemical properties (pH, osmolality, turbidity, viscosity) compatible with good ocular tolerance. Once defined, a physicochemical stability study testing pH, osmolality and dosage of biological factors, was carried out using the storage conditions usually used in clinical practice. A comparator without the additional compounds was also tested. The final formulation consisted of 20 % allogenic plasma, 0.5 % sodium hyaluronate (HS), 3 % trehalose (TH), 0.2 % chondroitin sulfate (CS) and 0.5 % sodium chloride (NaCl) (m/v). Its physicochemical properties should allow for good ocular tolerance. The data from the preliminary stability study favours storage at -20 °C for some of the biological factors measured.

Keywords:  Chondroitin; Formulation; Ocular surface disease; Ophthalmic solution; Plasma; Protective excipients; Sodium hyaluronate; Trehalose

DOI:  https://doi.org/10.1016/j.ejpb.2025.114813
New Phytol. 2025 Jul 24.

Brassinosteroid signaling promotes sulfate uptake under sulfur deficiency in Arabidopsis.

Xuanyi Chen, Zhenghao Yu, Wendi Guo, Yuting Zhou, Cun Wang, Tian Wang.

  Sulfur (S) is a crucial macronutrient for plant growth, development, and stress tolerance. It serves as an essential component of amino acids (cysteine and methionine), vitamins, sulfatides, and coenzymes. S deficiency impairs plant productivity; yet, the molecular mechanisms regulating sulfate uptake remain poorly understood. In this study, brassinosteroid (BR) signaling was found to be activated under S deficiency, leading to the nuclear accumulation of BZR1, a central transcription factor in the BR signaling. BZR1 expression increased at both the mRNA and protein levels under S deficiency conditions. SULTR1;2, a high-affinity sulfate transporter, was identified as a direct downstream target of BZR1 through in vitro and in vivo analyses. Genetic and physiological evidence demonstrated that BZR1 promotes sulfate uptake via SULTR1;2 in a BR-dependent manner. These findings uncover a molecular mechanism by which BR signaling regulates the S deficiency response through BZR1-mediated activation of SULTR1;2. This work enhances our understanding of nutrient signaling in Arabidopsis and provides potential targets for improving S use efficiency in crops.

Keywords:  Arabidopsis; BZR1; SULTR1;2; brassinosteroid signaling; sulfate transport

DOI:  https://doi.org/10.1111/nph.70390
Int J Biol Macromol. 2025 Jul 21. pii: S0141-8130(25)06768-6. [Epub ahead of print] 146211

Sulfation and carboxymethylation of Citrus medica 'Fingered' polysaccharides: Physicochemical properties and protective effects against LPS-induced intestinal barrier injury in Caco-2 cells.

Feng Xiong, Hong-Liang Yao, Yong-Hua Wu, Wen-Hao Hu, Yang-Hui Ou, Hou-Jin Li, Wen-Jian Lan.

  It is well known that Citrus medica 'Fingered' is an important industrial crop resource. Our previous study found that Citrus medica 'Fingered' polysaccharides via hot water extraction (HWE-CP) can alleviate ulcerative colitis by enhancing intestinal barrier and regulating intestinal flora. However, the large molecular weight of HWE-CP (35.15 kDa) limits its absorption by intestinal cells, thereby restricting its protective effects on the intestinal barrier. In this study, HWE-CP was chemically modified to obtain sulfated derivatives (S-HWE-CP) and carboxymethylated derivatives (C-HWE-CP). Subsequently, we investigated the physicochemical, structural characteristics, and protective abilities of these derivatives on the intestinal barrier. The results indicated that chemical modification led to significant changes in the molecular weight, monosaccharide composition and molar ratio, proportion of HG domains, Zeta potential, and thermal stability of HWE-CP. C-HWE-CP, with a degree of substitution of 1.12, most effectively promoted Occludin protein expression and enhanced the integrity of the cell barrier. Further analysis using RNA-seq revealed that C-HWE-CP may alleviate damage to Caco-2 cells through pentose and glucuronate interconversion pathways. These findings provide a theoretical basis for the role of HWE-CP functional group derivatives of HWE-CP in preventing chronic diseases associated with the intestinal barrier and facilitating the development of related functional foods.

Keywords:  Chemical modification; Citrus medica ‘fingered’; Intestinal barrier; Polysaccharides; RNA-seq

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.146211
New Phytol. 2025 Jul 23.

The GTE7-IES2B-GTE2 complex epigenetically regulates sulfur homeostasis in Arabidopsis thaliana.

Rong-Jian Luo, Chen-Jin Zhuo, Min Liang, Huan Liu, Xiao Gu, Fang-Jie Zhao, Xin-Yuan Huang.

  Maintaining sulfur (S) homeostasis is critical for plant growth and development, yet mechanisms regulating sulfate uptake remain poorly understood. We identify Global Transcription Factor Group E proteins, GTE7 and GTE2, along with the chromatin remodeling factor INO80 Subunit 2B (IES2B), as key regulators of S homeostasis in Arabidopsis thaliana. GTE7 directly binds to the Sulfur Response Element (SURE) in the promoter of the sulfate transporter gene SULTR1;1. The SURE flanking sequence undergoes dynamic DNA methylation in response to S status, with hypermethylation under S-sufficient conditions and hypomethylation under S-deficient conditions. GTE7 and its homolog GTE2 exhibit functional redundancy in suppressing sulfate accumulation in shoots. The gte7 gte2 double mutants displayed increased sulfate accumulation in shoots and impaired root growth. IES2B, a subunit of the INO80 chromatin remodeling complex, interacts with both GTE7 and GTE2, forming a regulatory complex that modulates dynamic DNA methylation at the SULTR1;1 promoter. Disruption of IES2B abolished S-resupply-induced DNA remethylation and elevated sulfate accumulation in shoots. Our findings reveal a GTE7-IES2B-GTE2 module that likely integrates transcriptional regulation and dynamic DNA methylation to fine-tune sulfate homeostasis, providing insights into the complex network of transcriptional and epigenetic regulation in response to S availability.

Keywords:  GTE2; GTE7; IES2B; epigenetic regulation; sulfate transporter; sulfur

DOI:  https://doi.org/10.1111/nph.70398
J Pathol. 2025 Jul 23.

Enhanced diagnostic potential of CSPG4 in melanoma and nevi: a comparative study with PRAME, CDC7 and Ki67.

Elias At Koch, Christina Seidel, Ramona Erber, Michael Erdmann, Markus V Heppt, Stefan Schliep, Carola Berking, Jan Dörrie, Niels Schaft.

  Chondroitin sulfate proteoglycan 4 (CSPG4) is a promising target for melanoma immunotherapy, but its expression in benign melanocytic lesions and its diagnostic value remain unexplored. This study assessed CSPG4 expression in benign nevi (BN), dysplastic nevi (DN), and superficial spreading melanomas (SSM), comparing it with PRAME (PReferentially expressed Antigen in MElanoma) and evaluating the cell division cycle 7-related protein kinase (CDC7) and the proliferation marker Ki67. Histological sections were stained using automated instruments, digitized, and analyzed using QuPath. Cohorts of BN, DN, and SSM were created, and positive cells/mm2 and H-scores were determined. A total of 336 IHC stainings from 84 specimens were analyzed. CSPG4 expression was readily detected in SSM and was significantly stronger in DN (p = 0.005), with the highest intensity observed in BN (p < 0.001). PRAME showed the highest density of positive cells/mm2 in SSM, was significantly reduced in DN (p < 0.001), and was lowest in BN (p < 0.001). Ki67 expression was strong in SSM, moderate in DN (p = 0.62), and low in BN (p = 0.008). CDC7 expression was most intense in DN, less in SSM (p = 0.39), and weakest in BN (p = 0.002). ROC AUC values for SSM versus DN and SSM versus BN were 0.764 and 0.921 for CSPG4, 0.85 and 0.889 for PRAME, 0.735 and 0.742 for Ki67, and 0.425 and 0.767 for CDC7. While PRAME was the most reliable marker for differentiating DN and SSM, CSPG4 was superior for distinguishing BN from SSM due to its high expression in BN. However, CSPG4-targeting therapies may trigger on-target/off-tumor effects due to its high expression in melanocytic nevi. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Keywords:  CDC7; CSPG4; Ki67; PRAME; benign nevus; dysplastic nevus; immunohistochemistry; melanoma

DOI:  https://doi.org/10.1002/path.6450
Front Mol Biosci. 2025 ;12 1593708

Raider of the lost N-glycans - Localizing rare and frequently overlooked IgG N-glycans with sulfation or bisecting LacNAc.

Robert Burock, Léa Chuzel, Thilo Kähne, Udo Reichl, Erdmann Rapp, René Hennig.

  Immunoglobulin G (IgG) is the most abundant immunoglobulin in human blood. Here it plays a central role in the immune system by recognizing antigens and mediating effector functions of the humoral immune defense. The role of IgG N-glycosylation in many of these processes is well known. However, low-abundant N-glycans with special features, like sulfation or galactosylated bisecting N-acetylglucosamine (GlcNAc), are rarely accounted for due to their challenging detection. These structures are frequently overlooked and their presence on IgG is disputed mainly because specialized enrichment and analysis strategies are required for their detection. Consequently, they are disregarded in studies of IgG N-glycosylation, which in general is well understood. But functional knowledge is mainly based on N-glycans found in IgGs Fc region that contains a conserved N-glycosylation site. In contrast, the influence of N-glycosylation within the Fab region is less well understood, partly because it is present at non-conserved glycosylation sites found on only 10%-25% of IgG. Here, we performed an in-depth analysis of released N-glycans derived from intact IgG, its Fab and its Fc regions. For this we combined proteolytic fragmentation of IgG obtained by affinity chromatography and exoglycosidase sequencing based on multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF). By using these simple and readily available methods, we localized N-glycans bearing sulfation or galactosylated bisecting GlcNAc on IgG, and found them on IgA, too. Further, we proved sulfation of N-glycans using an apo-sulfatase in an epitope-directed glycan enrichment (EDGE-) profiling workflow. With our novel findings, we provide insights into hypothetical biological implications of these low-abundant N-glycan features and advocate for their inclusion in future studies of IgG N-glycosylation.

Keywords:  Fab N-glycosylation; Fc N-glycosylation; IgG N-glycosylation; bisecting LacNAc; sulfatase; sulfated N-glycans; sulfation; xCGE-LIF

DOI:  https://doi.org/10.3389/fmolb.2025.1593708
Small. 2025 Jul 20. e04384

Bioactive Polysulfate-Based Nano-Assemblies Against Virus Infection.

Guoxin Ma, Mathias Dimde, Kai Ludwig, Latifa Abidal, Julia M Adler, Ricardo Martin Vidal, Benedikt B Kaufer, Jakob Trimpert, Chuanxiong Nie, Rainer Haag.

  3D nanosystems equipped with polysulfates as binding sites are effective virus inhibitors due to their ability to dynamically deform while adhering to a virus. Here, a new supramolecular nanosystem assembled from a block copolymer consisting of sulfated linear polyglycerol and polytrimethylene carbonate is presented. It exhibits a unique morphology, 100 nm sized spheres with a distinct brush-like corona. The negatively charged sulfates are distributed on the outer shell and enable exceptional homogeneity of the particles, thereby enhancing the efficiency of multivalent interactions. Various sulfation levels are tested and demonstrated extremely low half-maximal inhibition concentration (IC50) values in plaque reduction assays tested on herpes simplex virus type-1 (HSV-1): 0.43, 0.16, and 0.037 µg mL-1 of the 45%, 76% and 100% sulfated assemblies, respectively. Using cryo electron microscopy (cryo-EM), viruses trapped are observed by multiple layers of the nano-assemblies. Both 76% and 100% sulfated assemblies show therapeutic potential in the post-infection model. The inhibitory behavior of the 76% and 100% sulfated assemblies is further confirmed against Omicron infection. This work demonstrates that the presented 3D flexible nano-assemblies can block the virus entry into the host cells with superior morphology and efficiency, establishing them as a promising candidate for antiviral applications.

Keywords:  antiviral nanoassembly; multivalent nanosystems; polysulfates; virus inhibition

DOI:  https://doi.org/10.1002/smll.202504384
Mar Drugs. 2025 Jun 25. pii: 265. [Epub ahead of print]23(7):

Cladolosides of Groups S and T: Triterpene Glycosides from the Sea Cucumber Cladolabes schmeltzii with Unique Sulfation; Human Breast Cancer Cytotoxicity and QSAR.

Alexandra S Silchenko, Elena A Zelepuga, Ekaterina A Chingizova, Ekaterina S Menchinskaya, Kseniya M Tabakmakher, Anatoly I Kalinovsky, Sergey A Avilov, Roman S Popov, Pavel S Dmitrenok, Vladimir I Kalinin.

  Four new minor monosulfated triterpene penta- and hexaosides, cladolosides S (1), S1 (2), T (3), and T1 (4), were isolated from the Vietnamese sea cucumber Cladolabes schmeltzii (Sclerodactylidae, Dendrochirotida). The structures of the compounds were established based on extensive analysis of 1D and 2D NMR spectra as well as HR-ESI-MS data. Cladodosides S (1), S1 (2) and T (3), T1 (4) are two pairs of dehydrogenated/hydrogenated compounds that share identical carbohydrate chains. The oligosaccharide chain of cladolosides of the group S is new for the sea cucumber glycosides due to the presence of xylose residue attached to C-4 Xyl1 in combination with a sulfate group at C-6 MeGlc4. The oligosaccharide moiety of cladolosides of the group T is unique because of the position of the sulfate group at C-3 of the terminal sugar residue instead of the 3-O-Me group. This suggests that the enzymatic processes of sulfation and O-methylation that occur during the biosynthesis of glycosides can compete with each other. This can presumably occur due to the high level of expression or activity of the enzymes that biosynthesize glycosides. The mosaicism of glycoside biosynthesis (time shifting or dropping out of some biosynthetic stages) may indicate a lack of compartmentalization inside the cells of organism producers, leading to a certain degree of randomness in enzymatic reactions; however, this also offers the advantage of providing chemical diversity of the glycosides. Analysis of the hemolytic activity of a series of 26 glycosides from C. schmeltzii revealed some patterns of structure-activity relationships: the presence or absence of 3-O-methyl groups has no significant impact, hexaosides, which are the final products of biosynthesis and predominant compounds of the glycosidic fraction of C. schmeltzii, are more active than their precursors, pentaosides, and the minor tetraosides, cladolosides of the group A, are weak membranolytics and therefore are not synthesized in large quantities. Two glycosides from C. schmeltzii, cladolosides D (18) and H1 (26), display selectivity of cytotoxic action toward triple-negative breast cancer cells MDA-MB-231, while remaining non-toxic in relation to normal mammary cells MCF-10A. Quantitative structure-activity relationships (QSAR) were calculated based on the correlational analysis of the physicochemical properties and structural features of the glycosides and their hemolytic and cytotoxic activities against healthy MCF-10A cells and cancer MCF-7 and MDA-MB-231 cell lines. QSAR highlighted the complexity of the relationships as the cumulative effect of many minor contributions from individual descriptors can have a significant impact. Furthermore, many structural elements were found to have different effects on the activity of the glycosides against different cell lines. The opposing effects were especially pronounced in relation to hormone-dependent breast cancer cells MCF-7 and triple-negative MDA-MB-231 cells.

Keywords:  Cladolabes schmeltzii; Dendrochirotida; QSAR; Sclerodactylidae; hemolytic and cytotoxic activity; human breast cancer; sea cucumber; triterpene glycosides

DOI:  https://doi.org/10.3390/md23070265
Toxins (Basel). 2025 Jul 01. pii: 334. [Epub ahead of print]17(7):

Associations Between Uraemic Toxins and Gut Microbiota in Adults Initiating Peritoneal Dialysis.

Philippa James, Jordan Stanford, Ojas V A Dixit, Mary Ann Nicdao, Brett McWhinney, Kamal Sud, Michele Ryan, Scott Read, Golo Ahlenstiel, Kelly Lambert, Claire O'Brien, Katrina Chau.

  Declining kidney function contributes to the accumulation of uraemic toxins produced by gut microbiota, leading to the uraemic syndrome. This study aimed to identify associations between uraemic toxins, diet quality, symptoms and the gut microbiota in individuals initiating peritoneal dialysis. A cross-sectional analysis of baseline data from participants in a longitudinal study was conducted. Symptom scores using the Integrated Palliative Care Outcomes Scale-Renal were recorded. Plasma p-Cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide were measured using liquid chromatography-mass spectrometry. Gut microbiota was determined using 16S rRNA sequencing. Multivariate linear models examined associations across the cohort. Data from 43 participants (mean age 61 ± 13 years; 70% male; median eGFR 7 mL/min/1.73 m2) were analysed. Diabetes was the primary cause of kidney disease (51.2%). Patients were classified into 'high' (n = 18) and 'low' (n = 26) uraemic toxin groups using K-means clustering. The 'high' group had a lower eGFR (p < 0.05) but no differences in diet quality or symptom scores. Significant differences in alpha and beta diversity were observed between the groups (p = 0.01). The 'high' group had increased Catenibacterium, Prevotella, Clostridia, and decreased Ruminococcus gnavus abundances. Multivariate models identified 32 genera associated with uraemic toxins, including positive associations of Oscillospiraceae UCG-002 and UCG-005 with p-cresyl sulfate, and negative associations with Actinomyces and Enterococcus. Patients with kidney failure initiating peritoneal dialysis have distinct uraemic toxin profiles, associated with differences in microbial diversity. This phenotype was also associated with differences in residual kidney function but not with diet or symptom severity. Longitudinal studies are required to determine causality and guide therapeutic interventions.

Keywords:  chronic kidney disease; diet therapy; gut microbiome; kidney failure; peritoneal dialysis; uraemic toxin

DOI:  https://doi.org/10.3390/toxins17070334
Front Microbiol. 2025 ;16 1535356

The influence of gut microbiota on the gut-brain-kidney axis and its implications for chronic kidney disease.

Jue Zhu, Yutong Fu, Chinasa Valerie Olovo, Jianguo Xu, Qian Wu, Wei Wei, Ke Jiang, Xueming Zheng.

  The gut-brain-kidney axis represents a dynamic interplay among the gut microbiota, renal function, and neurological processes, emerging as a critical factor in chronic kidney disease (CKD) pathophysiology. This paper reviews recent data on the mechanisms and pathways that integrate gut-brain-kidney signaling and communication, advances in our understanding of this axis, and potential diagnostic and prognostic biomarkers and interventions for CKD. Literature search was conducted on PubMed, Scopus, Web of Science, and Embase using a combination of the keywords gut microbiota, gut microbiome, gut-brain axis, gut-kidney axis, gut-brain-kidney axis, chronic kidney disease, dysbiosis, therapy, metabolites, and neuroinflammation." Relevant studies were selected and synthesized in this narrative review. Gut dysbiosis, characterized by microbial composition and function alterations, contributes to systemic inflammation and metabolic imbalances, exacerbating CKD progression. Uremic toxins such as indoxyl sulfate and p-cresyl sulfate, derived from microbial metabolism, impair kidney function and disrupt neurocognitive health via oxidative stress and neuroinflammation, highlighting the interconnectedness of these systems. Recent advances in high-throughput sequencing and metabolomics have elucidated mechanisms linking gut microbiota and associated metabolites to kidney and brain health, revealing the role of microbial diversity and metabolite profiles in disease outcomes. Studies demonstrate that probiotics, prebiotics, and dietary interventions targeting the gut microbiota can modulate systemic inflammation and reduce uremic toxin levels, offering therapeutic potential. Understanding the bidirectional signaling within the gut-brain-kidney axis opens avenues for novel biomarkers and interventions in CKD management.

Keywords:  chronic kidney disease; gut microbiota; gut-brain-kidney axis; metabolites; therapy

DOI:  https://doi.org/10.3389/fmicb.2025.1535356