bims-supasi 2025-04-13 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2025–04–13
eight papers selected by
Jonathan Wolf Mueller, University of Birmingham

Astrocyte Extracellular Matrix Modulates Neuronal Dendritic Development.
Synthesis and Characterization of Phase-Separated Extracellular Condensates in Interactions with Cells.
A Case-Control Study of the Association of Novel Androgens (11-KT and DHT), Classical Androgens (Testosterone and DHEAS), Hormones (LH, FSH, 17-OHP, Insulin, and SHBG), Insulin Resistance (HOMA-IR), and Dyslipidemia in Polycystic Ovarian Syndrome (PCOS).
Evaluating serum S-Equol, indoxyl sulfate, and TMAO in predicting urinary stones in children: a prospective study.
Vascular inflammation in chronic kidney disease: the role of uremic toxins in macrophage activation.
The effects of sulfate on the physiology, biochemistry, and intestinal transcriptome of Scylla paramamosain under low-salinity conditions.
Recent advances of edible marine algae-derived sulfated polysaccharides in antiviral treatments: challenges vs. opportunities.
Sulfonated and sulfated lignans/neolignans from an aqueous extract of Isatis indigotica roots.

Glia. 2025 Apr 07.

Astrocyte Extracellular Matrix Modulates Neuronal Dendritic Development.

Joel G Hashimoto, Nicholas Margolies, Xiaolu Zhang, Joshua Karpf, Yuefan Song, Natalie Gorham, Brett A Davis, Fuming Zhang, Robert J Linhardt, Lucia Carbone, Marina Guizzetti.

  Major developmental events occurring in the hippocampus during the third trimester of human gestation and neonatally in altricial rodents include rapid and synchronized dendritic arborization and astrocyte proliferation and maturation. We tested the hypothesis that signals sent by developing astrocytes to developing neurons modulate dendritic development in vivo. First, we altered neuronal development by exposing neonatal (third trimester-equivalent) mice to ethanol, which increased dendritic arborization in hippocampal pyramidal neurons. We next assessed concurrent changes in the mouse astrocyte translatome by translating ribosomal affinity purification (TRAP)-seq. We followed up on ethanol-inhibition of astrocyte Chpf2 and Chsy1 gene translation because these genes encode biosynthetic enzymes of chondroitin sulfate glycosaminoglycan (CS-GAG) chains (extracellular matrix components that inhibit neuronal development and plasticity) and have not been explored before for their roles in dendritic arborization. We report that Chpf2 and Chsy1 are enriched in astrocytes, and their translation is inhibited by ethanol, which also reduces the levels of CS-GAGs measured by Liquid Chromatography/Mass Spectrometry. Finally, astrocyte-conditioned medium derived from Chfp2-silenced astrocytes increased neurite length and branching of hippocampal neurons in vitro, mechanistically linking changes in CS-GAG biosynthetic enzymes in astrocytes to altered neuronal development. These results demonstrate that CS-GAG biosynthetic enzymes in astrocytes regulate dendritic arborization in developing neurons and are involved in ethanol-induced altered neuronal development.

Keywords:  astrocyte translatome; chondroitin sulfate glycosaminoglycans (CS‐GAGs); dendrite development; ethanol; fetal alcohol Spectrum disorders (FASD); hippocampus

DOI:  https://doi.org/10.1002/glia.70020
bioRxiv. 2025 Mar 26. pii: 2025.03.24.644961. [Epub ahead of print]

Synthesis and Characterization of Phase-Separated Extracellular Condensates in Interactions with Cells.

Aida Naghilou, Tom M J Evers, Oskar Armbruster, Vahid Satarifard, Alireza Mashaghi.

Biomolecular condensates formed through liquid-liquid phase separation play key roles in intracellular organization and signaling, yet their function in extracellular environments remains largely unexplored. Here, we establish a model using heparan sulfate, a key component of the extracellular matrix, to study extracellular condensate-cell interactions. We demonstrate that heparan sulfate can form condensates with a positively charged counterpart in serum-containing solutions, mimicking the complexity of extracellular fluid, and supporting cell viability. We observe that these condensates adhere to cell membranes and remain stable, enabling a versatile platform for examining extracellular condensate dynamics and quantifying their rheological properties as well as their adhesion forces with cellular surfaces. Our findings and methodology open new avenues for understanding the organizational roles of condensates beyond cellular boundaries.

DOI: https://doi.org/10.1101/2025.03.24.644961
Adv Biomed Res. 2025 ;14 2

A Case-Control Study of the Association of Novel Androgens (11-KT and DHT), Classical Androgens (Testosterone and DHEAS), Hormones (LH, FSH, 17-OHP, Insulin, and SHBG), Insulin Resistance (HOMA-IR), and Dyslipidemia in Polycystic Ovarian Syndrome (PCOS).

Nirmal Kumar, Neera Sharma, Smita Roy, Indu Chawla, Lokesh Kumar Sharma.

   Background: The measurement of androgens (testosterone and dehydroepiandrosterone sulfate (DHEAS)) remains standard for the evaluation of polycystic ovarian syndrome (PCOS) women. However, other early novel androgen markers, 5 alpha-dihydrotestosterone (DHT) and 11-ketotestosterone (11-KT), may open a separate path of measurement, which may be more potent. The study was conducted with the objectives to analyze the association of 11-KT and DHT with established markers and with the clinical profile of PCOS patients.
Materials and Methods: A case-control study was conducted on 30 newly diagnosed cases of PCOS as per the Rotterdam criteria and 30 age-matched controls. The estimation of testosterone, DHEAS, 11-KT, and DHT was performed by the enzyme-linked immunoassay (ELISA) method. The assessment of biochemical and hormonal parameters was compared and correlated with 11-KT and DHT.
Results: Compared to the controls, cases had significantly higher 11-KT (20.81 ± 3.53 vs. 15.83 ± 2.67 nmol/L, P < 0.0001) and DHT (154.39 vs. 71.02 pg/mL, P < 0.0001). 11-KT showed a significant positive correlation with total testosterone (TT) (r = 0.555) and DHEAS (r = 0.501). DHT also showed a significant positive correlation with TT (r = 0.487) and DHEAS (r = 0.52).
Conclusion: In conclusion, novel androgen derivatives (11-KT and DHT) hold equivalent evidence for the evaluation of women with PCOS as they are raised in women with PCOS as compared to controls. Moreover, they show a good correlation with the standard markers currently used for PCOS.

Keywords:  Androgens; dehydroepiandrosterone; diagnosis; dihydrotestosterone; insulin; ovary; sex hormone-binding globulin; testosterone

DOI:  https://doi.org/10.4103/abr.abr_262_23
Urolithiasis. 2025 Apr 05. 53(1): 68

Evaluating serum S-Equol, indoxyl sulfate, and TMAO in predicting urinary stones in children: a prospective study.

Aylin Gencler, Hakim Celik, Abit Demir.

  Gut microbiota is vital in maintaining health and has been implicated in urinary stone disease. Patients with and without stones have different microbial compositions. In this context, we assessed serum levels of S-equol, indoxyl sulfate (IS), and trimethylamine N-oxide (TMAO), which are metabolites thought to be associated with gut microbiota, and their prognostic values in predicting stone formation in children with urinary stone disease. The study population consisted of children aged between one month and 18 years with urinary stone disease. The patient group consisted of 44 children with urinary stone disease, and the control group consisted of 44 healthy children who were matched with the patient group in terms of age and gender. The study's primary outcomes were the differences between the groups in serum metabolite levels. Serum S-equol and TMAO levels were significantly lower in the patient group than in the control group. There was no significant difference between the groups in serum IS levels. There were also no significant correlations between serum metabolite levels and age in either group. Children with urinary stone disease had significantly lower serum S-equol and TMAO levels than healthy control subjects, suggesting a possible link between these metabolites and stone formation.

Keywords:  Gut microbiota; Indoxyl sulfate; Metabolites; Pediatric nephrolithiasis; S-equol; Trimethylamine N-oxide; Urinary stone disease

DOI:  https://doi.org/10.1007/s00240-025-01737-w
Front Cardiovasc Med. 2025 ;12 1574489

Vascular inflammation in chronic kidney disease: the role of uremic toxins in macrophage activation.

Prabhash Kumar Jha, Toshiaki Nakano, Lucas Yuji Umesaki Itto, Miguel Cantadori Barbeiro, Adrien Lupieri, Elena Aikawa, Masanori Aikawa.

  Chronic kidney disease (CKD) is a progressive condition characterized by the gradual loss of kidney function, leading to the accumulation of uremic toxins in the bloodstream. These toxins play a pivotal role in mediating vascular inflammation, a key contributor to the high cardiovascular morbidity and mortality observed in CKD patients. This review article explores the intricate mechanisms by which uremic toxins accelerate vascular inflammation. Macrophages, as versatile immune cells, are central to the inflammatory response. Evidence suggests that the uremic milieu influences macrophage biology. In this review article, we focus on the signaling through which uremic toxins, particularly indoxyl sulfate-an independent risk factor for cardiovascular complications in CKD patients, modulate macrophage activation and function, and how these changes contribute to vascular inflammation, leading to the increased cardiovascular risk. Investigation of such mechanisms provide molecular bases for the development of new therapies that retard the development of cardiovascular disorders in CKD patients.

Keywords:  cardiovascular risk; chronic kidney disease (CKD); end-stage renal disease (ESRD); indoxyl sulfate; inflammation; macrophages; uremic toxins; vascular disease

DOI:  https://doi.org/10.3389/fcvm.2025.1574489
Comp Biochem Physiol Part D Genomics Proteomics. 2025 Mar 30. pii: S1744-117X(25)00090-5. [Epub ahead of print]55 101502

The effects of sulfate on the physiology, biochemistry, and intestinal transcriptome of Scylla paramamosain under low-salinity conditions.

Gao Gao, Yun Hu, Kangxiang Qin, Ziwei Fan, Chunlin Wang, Huan Wang.

  Sulfate, a key component of seawater and sulfate-saline-alkali soil, critically impacts aquatic species' physiology. The aim of this experiment was to investigate the effects of sulfate concentration on the growth, survival, microstructure of gills and hepatopancreas, as well as the intestinal immune response and molecular mechanisms of Scylla paramamosain. The experimental groups were categorized as S1 (0 g/L sulfate, sulfate-free), S2 (1 g/L sulfate, optimal concentration), and S3 (2 g/L sulfate, high sulfate concentration). The results showed that with the increase of sulfate concentration in the experimental water, Survival and weight growth rates initially increased but declined at higher sulfate concentrations (P < 0.05), while molting rates progressively decreased. The intestinal ACP and AKP levels in S2 were significantly higher than those in S1 and S3 (P < 0.05). AST and ALT in the S2 group showed no significant difference from those in the S3 group (P > 0.05) but were significantly lower than those in the S1 group (P < 0.05). Sulfotransferases in the S2 group were significantly lower than those in the S1 and S3 groups (P < 0.05). Short-term (72 h) microscopic observations of the gills and hepatopancreas revealed that the gills in both the S1 and S3 groups exhibited thickening of the gill filaments and rupture of the cuticle layer, while the hepatopancreatic tissue in the S3 group also showed enlargement of intercellular spaces, fracture of the basement membrane, and blurred boundaries. Transcriptome sequencing of the S. paramamosain intestine revealed significant upregulation of sulfotransferases in both S1 and S3 groups. GO annotation of DEGs indicated similar responses of S. paramamosain to sulfate-free and high-sulfate environments, maintaining physiological stability by activating protein processing pathways, enhancing blood-lymph coagulation, and regulating redox balance. KEGG analysis revealed that sulfate-free environments predominantly enriched lipid metabolism and secondary metabolism pathways. While those enriched in high-sulfate environments were mainly related to amino acid metabolism and secondary metabolism. The results indicate that both sulfate-free and high-sulfate concentrations affect the growth, survival, and molting rates of S. paramamosain, as well as inducing immune responses in the intestine. In the short term, they can cause structural changes in the gills and hepatopancreas. The intestinal transcriptome expression shows a similar response pattern, but the metabolic pathways differ. This study provides theoretical support and technical guidance for the cultivation of S. paramamosain under low-salinity conditions with sulfate-type saline-alkali water.

Keywords:  Growth and survival; Immune responses; Molecular mechanisms; Sulfate; scylla paramamosain

DOI:  https://doi.org/10.1016/j.cbd.2025.101502
Front Nutr. 2025 ;12 1561119

Recent advances of edible marine algae-derived sulfated polysaccharides in antiviral treatments: challenges vs. opportunities.

Xiaoying Dong, Yusong Qiu, Nan Jia, Yinfeng Wu, Qing Nie, Jiahui Wen, Chao Zhao, Yongzhen Zhai.

  Marine polysaccharides, particularly those derived from red, brown, and green algae, have shown promising antiviral activity. Among them, sulfated polysaccharides are particularly notable due to their broad-spectrum antiviral properties. These include direct viral destruction, inhibition of virus adsorption, disruption of viral transcription and replication, and the stimulation of the host's antiviral immunity. With low toxicity, minimal drug resistance, and excellent biocompatibility, these polysaccharides represent promising candidates for the development of antiviral medications. For instance, carrageenan, a polysaccharide from red algae, and fucoidan, a polymer from brown algae, have both been proven to effectively inhibit viral infections. Sulfated polysaccharides from green algae, such as those found in Ulva species, also exhibit antiviral properties, including activity against the Japanese encephalitis virus. These polysaccharides function by blocking the attachment of viruses to host cells or interfering with various stages of the viral life cycle. Moreover, marine polysaccharides have been shown to enhance host immune responses, thereby aiding in viral clearance. Although these findings highlight the antiviral potential of marine polysaccharides, most studies have been conducted in vitro or in animal models. Further clinical trials are necessary to validate their effectiveness and safety for therapeutic use.

Keywords:  algae; antiviral mechanisms; marine polysaccharides; sulfated polysaccharides; virus

DOI:  https://doi.org/10.3389/fnut.2025.1561119
J Asian Nat Prod Res. 2025 Apr 11. 1-10

Sulfonated and sulfated lignans/neolignans from an aqueous extract of Isatis indigotica roots.

Jia-Yi Feng, Yu-Feng Liu, Xiao-Qiang Lei, Qing-Lan Guo, Jian-Gong Shi.

  Five sulfonated and sulfated lignans/neolignans (1-5), together with a neolignan analogue (6), were isolated from an aqueous extract of the Isatis indigotica roots (ban lan gen). Their structures were determined by spectral data analysis in combination with electronic circular dichroism (ECD) and NMR calculations. Among the isolates, 1 and 2 are sulfonated 7,9'-epoxylignans, while 3-5 are either sulfated or sulfonated 4',7-epoxy-8,3'-neolignans. In the preliminary bioassay, 2 and 3 exhibited moderate inhibitory activities against TGF-β induced HSC-T6 cell activation.

Keywords:  4′,7-epoxy-8,3′-neolignan-8′-sulfonic acid; 7,9′-epoxylignan-7′-sulfonic acid; 8′,9′-dinor-4′,7-epoxy-8,3′-neolignan-9-ol sulfate; Cruciferae; Isatis indigotica; inhibition against TGF-β induced HSC-T6 cell activation

DOI:  https://doi.org/10.1080/10286020.2025.2483810