bims-supasi 2025-08-24 papers

Curr Opin Biotechnol. 2025 Aug 14. pii: S0958-1669(25)00084-9. [Epub ahead of print]95 103340

From animal tissue to engineered cells: biotechnological advances in sulfated glycosaminoglycan production.

Aditi Dey Tithi, Yuefan Song, Hana Zeghal, Mattheos Koffas.

Biotechnological strategies are rapidly advancing the production of sulfated glycosaminoglycans (GAGs), such as chondroitin sulfate and heparin, offering animal-free alternatives with greater safety and structural control. This article examines key developments across microbial, enzymatic, and synthetic platforms, highlighting innovations in metabolic engineering, sulfotransferase optimization, and cofactor regeneration. Case studies in both chondroitin and heparin biosynthesis illustrate how systems biology and protein design are addressing long-standing bottlenecks. We also discuss current limitations and future directions needed to realize scalable, clinically relevant GAG bioproduction.

DOI: https://doi.org/10.1016/j.copbio.2025.103340

Nephrology (Carlton). 2025 Aug;30(8): e70109

Chondroitin Sulfate N-Acetylgalactosaminyltransferase 1 Promotes the Progression of Renal Fibrosis Mediated by Versican 1 in Mouse Remnant Kidney.

Yoshikatsu Kaneko, Yuya Suzuki, Kaho Sato, Kosei Takeuchi, Michihiro Igarashi, Ichiei Narita.

AIM: Renal fibrosis is a final common pathway for progressive chronic kidney diseases. Immune cell infiltration and production of tumour growth factor-β (TGF-β) are essential factors for fibrosis development. We examined the role of chondroitin sulfate (CS) proteoglycan, which is one of the main extracellular matrix components induced by TGF-β signalling. We also examined CS N-acetylgalactosaminyltransferase 1 (T1), an enzyme that catalyses the first step of CS-specific synthesis.
METHODS: T1-/- mice, genetically lacking T1, and T1+/+ mice underwent 5/6 nephrectomy (Nx) or sham operation. Kidney function, urine marker, mRNA expression, and TGF-β signalling were evaluated 1 month after Nx or sham operation. Renal fibrotic area was quantified 3 months later.
RESULTS: Both T1+/+ and T1-/- mice with Nx showed equivalent loss of kidney function; however, a tubular damage marker, upregulation of TGF-β and collagen expression, and renal fibrosis were suppressed in T1-/- mice with Nx. Versican, one of the core proteins of CS proteoglycan, was exclusively upregulated in T1+/+ mice with Nx. Among the versican splicing variants, versican 1 (V1) was expressed in the medullary interstitium of the remnant kidney in T1+/+ mice. V1 was produced in the interstitial macrophages, fibroblasts/myofibroblasts, and endothelial cells, whereas TGF-β was expressed in fibroblasts/myofibroblasts. Phosphorylation of the TGF-β signalling molecules Smad2/3 was not induced in T1-/- mice with Nx. In vivo administration of TGF-β inhibitor into Nx mice reduced V1 and Tgfb expression.
CONCLUSION: T1 was essential for effective TGF-β signalling, V1 upregulation, and subsequent renal fibrosis.

Keywords: Smad; TGF‐beta; chondroitin sulfate proteoglycan; collagen; nephrectomy

DOI: https://doi.org/10.1111/nep.70109

J Agric Food Chem. 2025 Aug 18.

Molecular Insight into the Inhibitory Effect of Sulfated Polysaccharide Fucoidan on Hyaluronidase Activity.

Zeyuan Feng, Jinwen Li, Shu Jie Li.

Hyaluronic acid in vivo serves a multitude of functions, including water retention and osmoregulation. Inhibition of hyaluronidase activity prevents the degradation of hyaluronic acid, thereby preserving its normal physiological functions. Fucoidan is a natural sulfated polysaccharide extracted from brown algae. Here, bovine testicular hyaluronidase was separated and purified as a basis for investigating the inhibitory effect of fucoidan on hyaluronidase activity. The experimental results showed that fucoidan exhibited strong competitive inhibition of hyaluronidase activity, with an IC50 value of 4.137 μM. Molecular docking demonstrated that fucoidan binds to the active site of hyaluronidase, with its sulfate groups forming hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations suggested that the complex formed by the binding of fucoidan to hyaluronidase was highly stable, with a binding energy of -24.59 kcal/mol, indicating a high affinity between fucoidan and hyaluronidase. The Ramachandran plot indicated that the binding of fucoidan to hyaluronidase results in a structural change in the active site of the enzyme, making its structure more inert and compact.

Keywords: activity; fucoidan; hyaluronidase; inhibition; interaction; molecular mechanism

DOI: https://doi.org/10.1021/acs.jafc.5c04257

Front Mol Biosci. 2025 ;12 1595173

Immunoglobulin A carries sulfated and O-acetylated N-glycans primarily at the tailpiece site - strategies for site-specific N-glycan identification.

Frania J Zuniga-Banuelos, Greta Lemke, Marcus Hoffmann, Udo Reichl, Erdmann Rapp.

Sulfated N-glycans from human immunoglobulin A (IgA) were recently discovered via glycomic approaches. However, their site-specific description is still pending. Certain N-glycan structures at specific N-glycosylation sites in IgA are crucial for microbial neutralization and effector functions. For instance, sialylated N-glycans on the C-terminal tailpiece mediate anti-viral activity by interfering with sialic-acid-binding viruses. Sulfated N-glycan epitopes can be ligands for viral proteins and thus play a role in the immune response. In this study, we performed a site-specific screening for sulfated and other rare N-glycans in two commercially available human serum IgA samples employing an in-depth N-glycoproteomic approach, previously developed by us. We found evidence of complex-type and hybrid-type N-glycans containing sulfated N-acetylhexosamine (sulfated HexNAc) attached to the N-glycosylation sites in the tailpiece and the CH2 domain of both IgA subclasses. Also, complex-type N-glycan compositions bearing O-acetylated sialic acid were identified primarily at the tailpiece site. Surprisingly, N-glycans bearing glucuronic acid were identified in the commercial IgA samples, but from peptides of "contaminant" glycoproteins. A detailed comparison of the N-glycosylation profiles of human serum IgA samples from two suppliers showed such N-glycans with sulfated HexNAc consistently in higher abundance in the tailpiece region. These findings have not been described before for a site-specific glycopeptide analysis. Overall, our work provides strategies for performing a dedicated site-specific search for sulfated and O-acetylated N-glycans that can be easily transferred, e.g., to human IgA derived from mucosal tissues, milk, or saliva. We expect that a wider and deeper micro-heterogeneity description of clinically relevant glycoproteins, such as immunoglobulins, can expand the screening for biomarkers or treatment options.

Keywords: N-glycosylation; O-acetylated N-glycans; glycoproteomics; immunoglobulin A (IgA); mass spectrometry; oxonium marker ions; rare N-glycans; sulfated N-glycans

DOI: https://doi.org/10.3389/fmolb.2025.1595173

Int J Biol Macromol. 2025 Aug 17. pii: S0141-8130(25)07421-5. [Epub ahead of print]322(Pt 3): 146864

Dextran sulfate-containing thermosensitive hydrogel improves tendon healing by modulating macrophage polarization.

Shih-Heng Chen, Po-Hao Lien, Chuan-Yan Sun, Pang-Yun Chou, Zhi-Yu Chen, Shih-Hsien Chen, Hsu-Wei Fang, Feng-Huei Lin.

Direct tendon repair is a prevailing management strategy for tendon rupture. However, healing is impeded by the relatively low metabolic activity of tendon cells and chronic inflammation following the initial injury and subsequent surgery. To address this challenge, we developed a thermosensitive Pluronic-dextran sulfate (PDS) hydrogel to mitigate chronic inflammation by modulating macrophage phenotypes and facilitating extracellular matrix deposition through the sulfated residue of the hydrogel. Rheometer test results revealed that the PDS hydrogel exhibited a phase transition at approximately 13 °C, facilitating rapid solidification upon contact with live tissue during intraoperative use. Additionally, the material complied with ISO-10993 standards, demonstrating non-cytotoxic properties. In vitro, the PDS hydrogel significantly increased tenocyte proliferation and migration by 33 % and 408 %, respectively, compared to those of the controls (p < 0.05). Gene expression analysis revealed a 4.1-fold increase (p < 0.05) in anti-inflammatory M2 marker expression (EGR-2) with a significant reduction (75 %) in IL-1β levels (p < 0.05). In vivo studies demonstrated the biocompatibility of the material, as evidenced by the absence of liver and kidney toxicity. In vivo rabbit Achilles tendon repair models showed that the PDS group exhibited a significantly higher tendon-breaking force (179.8 ± 50.3 N) than the control group (52.6 ± 20.0 N) (p < 0.05). Data from mechanical tests of the repaired tendons, as well as reverse transcription-polymerase chain reaction analysis, further validated that the PDS hydrogel promoted tendon healing and that it has potential for modulating macrophage polarization.

Keywords: Hydrogel; Macrophage; Pluronic-dextran sulfate; Tendon healing

DOI: https://doi.org/10.1016/j.ijbiomac.2025.146864

Front Endocrinol (Lausanne). 2025 ;16 1606949

A cross-sectional study of testosterone deficiency and inflammatory markers in older men.

Iwona Rotter, Żaneta Ciosek, Anna Syroka, Aleksandra Ryl.

Background: This cross-sectional study aimed to examine the relationship between total testosterone (TT) levels, the diagnosis of testosterone deficiency syndrome (TDS), and high-sensitivity C-reactive protein (hsCRP) concentrations in aging men. The analysis also included selected hormonal and anthropometric parameters.
Methods: Serum hsCRP levels were measured. Additionally, serum levels of TT, estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), insulin (I), and sex hormone-binding protein (SHBG) were assessed using ELISA. Patients were divided based on the presence or absence of a TDS diagnosis.
Results: In patients without TDS, no significant correlation was observed between hsCRP levels and other measured variables. However, higher hsCRP levels were associated with an increased BMI, larger waist and hip circumferences, and elevated triglyceride (TAG) levels compared to patients with lower hsCRP concentrations.
Conclusions: The co-occurrence of testosterone deficiency and elevated inflammatory markers such as hsCRP was associated with less favorable metabolic and anthropometric profiles. While causality cannot be inferred from this observational study, the findings suggest a possible link between systemic inflammation and testosterone deficiency in aging men. These associations merit further investigation in longitudinal and mechanistic studies to clarify directionality and underlying biological pathways.

Keywords: Hs-CRP; aging men; deficiency; hormonal; testosterone

DOI: https://doi.org/10.3389/fendo.2025.1606949