bims-supasi 2026-04-19 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–04–19
eighteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Synthesis of sulfated α-(1→4)-ʟ-idose oligosaccharides as heparan sulfate mimetics and their interactions with fibroblast growth factors.
Impact of CSGALNACT1-mediated structural changes in chondroitin sulfate on tau seed uptake and pathological progression.
MESH1 regulates sulfation through the hydrolysis of PAPS.
Synthesis of and characterization of differentially sulfated disaccharide repeating units of keratan sulfate.
Development of a sensitive and specific method to measure heparanase activity in complex biological matrices.
Evaluation of the antifungal efficacy of microbial chondroitin sulfate against candida species in an experimental rat model of vulvovaginal candidiasis.
Chemically Engineered Sulfates of Lasiodiplodan: Antioxidant, Antimicrobial, and Antirespiratory Syncytial Virus (RSV) Activities.
Low serum dehydroepiandrosterone sulfate is related to diabetic retinopathy in males with type 2 diabetes mellitus.
6-O-Sulfated glycopolymer promotes osteogenesis by amplifying BMP-2 signaling via specific upregulation of BMP receptors.
Diagnostic Utility of ACTH, Cortisol, DHEAS, and Their Derived Ratios in Cushing's Syndrome Subtypes.
Evolutionary and Transcriptomic Analyses of the Plant TPST-Sulfated Peptides System, with Insights from Woody Liriodendron chinense.
Dynamic structures of dengue virus serotype 2 secreted NS1 and their interactions with heparan sulfate.
A low-cost disposable label-free immunosensor for high-performance detection of indoxyl sulfate using chitosan based tertiary nanocomposite.
Quantification of glycosaminoglycans in dried blood spots, and evaluation of its usefulness as a secondary newborn screening test for mucopolysaccharidoses.
Severe hyperandrogenism and mild autonomous cortisol secretion from a functional lipid-poor adrenal cortical adenoma.
Fully Synthetic Non-Carbohydrate Heparin Mimetics-Perspectives for Therapeutic Anticoagulation and Beyond?
miR-4516-Loaded Engineered Milk Extracellular Vesicles Attenuate Indoxyl Sulfate-Induced Mitochondrial Dysfunction and Improve Renal Function in a CKD Mouse Model.
Effect of androgens on retinal microvasculature in prepubertal girls with isolated premature pubarche.

Bioorg Chem. 2026 Apr 06. pii: S0045-2068(26)00376-7. [Epub ahead of print]176 109840

Synthesis of sulfated α-(1→4)-ʟ-idose oligosaccharides as heparan sulfate mimetics and their interactions with fibroblast growth factors.

Yi-Chen Liao, Jasper S Dumalaog, Cheng-Hsiu Chang, Shang-Cheng Hung.

  Heparan sulfate (HS) is an essential glycosaminoglycan involved in key physiological processes, including cell signaling, coagulation, and growth factor regulation. Its specific sulfonation patterns and conformational flexibility enable interactions with various proteins. However, the structural complexity of natural HS poses significant challenges for detailed study and therapeutic applications. In this study, we present a chemical synthesis approach for α-1→4-linked ʟ-idose (ʟ-Ido) homooligosaccharides designed to mimic the structure and function of HS. The synthesized oligosaccharides, ranging from mono- to tetrasaccharides, incorporate 2-O- and 6-O- sulfation, reflecting native HS sulfation patterns. A series of protection, stereoselective glycosylation, and functional group transformations yielded well-defined structures for structure-activity relationship (SAR) studies. Binding interactions with fibroblast growth factors 1 and 2 (FGF-1 and FGF-2) were evaluated using isothermal titration calorimetry (ITC), revealing that the trisaccharide and tetrasaccharide analogues bind to both growth factors. Furthermore, in silico molecular docking analysis indicated that the 2,6-di-O-sulfate groups form key electrostatic interactions with basic residues in the binding sites of both FGFs. These results highlight the potential of ʟ-Ido oligosaccharides as well-defined HS mimetics for probing and modulating FGF-HS interactions.

Keywords:  Carbohydrate binding; Growth factors; Heparan sulfate; Mimetics; Oligosaccharides

DOI:  https://doi.org/10.1016/j.bioorg.2026.109840
Biochim Biophys Acta Gen Subj. 2026 Apr 16. pii: S0304-4165(26)00051-6. [Epub ahead of print]1870(7): 130951

Impact of CSGALNACT1-mediated structural changes in chondroitin sulfate on tau seed uptake and pathological progression.

Satomi Nadanaka, Jun-Ichi Tamura, Hiroshi Kitagawa.

  Chondroitin sulfate (CS) plays essential roles in neurodevelopment and brain aging. Alterations in glycosaminoglycan composition on the neuronal cell surface and within the extracellular matrix (ECM) contribute to the progression of tauopathies, including Alzheimer's disease (AD). Disease-associated changes in CS sulfation patterns have been linked to tau pathology, and administration of CS-specific antibodies has been shown to improve cognitive function in AD model mice. CSGALNACT1 catalyzes the initial step of CS chain elongation by transferring N-acetylgalactosamine residues to the linkage tetrasaccharide. Although csgalnact1-deficient mice exhibit structural alterations in perineuronal nets-specialized ECM structures surrounding neurons-as well as suppression of inflammatory diseases, the relevance of CSGALNACT1 to human neurodegenerative disorders remains unclear. Here, we investigated the role of CSGALNACT1 in AD by integrating human brain transcriptomic analyses with cell-based assays. We found that CSGALNACT1 expression decreased during healthy aging but was maintained or upregulated in AD brains in association with pathological progression. In Neuro2a cells, we observed CS-dependent tau seed uptake, which was significantly enhanced by CSGALNACT1 overexpression. Disaccharide analysis further revealed that CSGALNACT1 expression increased the abundance of non-sulfated CS disaccharide units (O units). Moreover, CS synthesized by CSGALNACT1 exhibited high affinity for both tau seeds and wild-type tau monomers and promoted tau aggregation in vitro. Together, these findings demonstrate that O unit-enriched CS chains generated by CSGALNACT1 facilitate extracellular tau capture, cellular uptake, and aggregation, thereby promoting tau pathology progression. This study identified CS structural regulation as a critical determinant of AD onset and progression.

Keywords:  Alzheimer's disease; CSGALNACT1; Chondroitin sulfate; Extracellular matrix; Glycosaminoglycans; Tau aggregation; Tauopathy

DOI:  https://doi.org/10.1016/j.bbagen.2026.130951
Nat Chem Biol. 2026 Apr 16.

MESH1 regulates sulfation through the hydrolysis of PAPS.

DOI: https://doi.org/10.1038/s41589-026-02191-4
Glycosci Ther. 2026 Mar;pii: 100023. [Epub ahead of print]2(1):

Synthesis of and characterization of differentially sulfated disaccharide repeating units of keratan sulfate.

Anupama Das, Gustavo A Kashiwagi, Qi Gan, Melanie L Shadrick, Adriana M Montaño, Alexei V Demchenko.

  Keratan sulfate (KS) is a member of a broad family of sulfated polysaccharides known as glycosaminoglycans. Synthetic KS derivatives can lead to the advancement in early detection of mucopolysaccharidoses disorders using mass spectrometry. Reported herein is the synthesis of all four differentially sulfated keratan sulfate disaccharide repeat units. The efficient synthetic strategies to obtain non-sulfated, two different monosulfated, and disulfated derivatives has been developed. In accordance with our retrosynthetic analysis, all backbone disaccharide intermediates were synthesized from unique glycosyl donors and the universal glycosyl acceptor. Final purification of target compounds was accomplished by size exclusion chromatography, and all compounds were thoroughly characterized.

Keywords:  Carbohydrates; Characterization; Protection groups; Synthesis

DOI:  https://doi.org/10.1016/j.glycos.2025.100023
Glycobiology. 2026 Apr 14. pii: cwag028. [Epub ahead of print]

Development of a sensitive and specific method to measure heparanase activity in complex biological matrices.

Zhangjie Wang, Robert Richter, Guowei Su, Yongmei Xu, Yannic Becker, Hermann Haller, Jian Liu.

  Heparanase-1 (HPSE) is the only mammalian endo-β-D-glucuronidase that cleaves heparan sulfate (HS) polysaccharides on cell surfaces and in extracellular matrices. HPSE contributes to diverse pathological conditions, particularly in the processes driving injury to the luminal glycocalyx overlying vascular endothelial cells. Existing methods for assaying the activity of HPSE are insensitive and lack specificity. Here, we present a new method, Single Heparan Sulfate Substrate-Based Isotope Dilution Mass Spectrometry (SHS-IDMS), that permits the quantitative measurement of HPSE activity in complex biological matrices like plasma. The method involves the use of a structurally defined-HS 12-mer substrate that yields a consistent disaccharide product upon HPSE digestion. The disaccharide product is quantified using LC-MS/MS and a 13C-labeled disaccharide calibrant. The method demonstrates strong linearity, high sensitivity, and resistance to interference by heparanase-2 (HPSE-2). Using this method, we detected significant, quantitative differences in HPSE activity using 20 μL plasma samples from children with sepsis compared to samples from healthy children. Moreover, we found that plasma HPSE activity correlated with circulating levels of syndecan-1 and angiopoietin-2, supporting the hypothesis that HPSE may contribute to endothelial glycocalyx injury and pathological endothelial activation under septic conditions. The new method will advance research in the biology of this important enzyme.

Keywords:  Heparan sulfate; Heparanase; SHS-IDMS; sepsis

DOI:  https://doi.org/10.1093/glycob/cwag028
Sci Rep. 2026 Apr 17.

Evaluation of the antifungal efficacy of microbial chondroitin sulfate against candida species in an experimental rat model of vulvovaginal candidiasis.

Rauf Melekoglu, Ayse Sebnem Erenler, Mustafa Huz, Tuba Unver, Feyza Inceoglu, Suleyman Koytepe, Hikmet Geckil, Nusret Akpolat.

  Chondroitin sulfate (CS) is a glycosaminoglycan with various biological functions including antioxidant and anti-inflammatory effects. Candida species, particularly Candida albicans, are major pathogens involved in vulvovaginal candidiasis (VVC), which affects a majority of women, and novel antifungal agents are needed due to the limitations of current treatments. This study evaluated the antifungal efficacy of microbial chondroitin sulfate (MCS), produced via recombinant Escherichia coli (C2987), in a rat model of VVC. MCS was biosynthesized via the pETM6-PACF-vgb+ plasmid harboring the kfoA, kfoC, kfoF, and vgb genes, and its structural integrity and composition were confirmed via NMR, HPLC, and FT-IR. VVC was induced in immunosuppressed, estrogen-treated Wistar albino rats, which were randomized into eight groups: uninoculated control, infected untreated control, cream base, nystatin, fenticonazole, and MCS at 0.1%, 0.5%, and 1.0%, respectively. Topical treatments were applied for seven days, and the vaginal fungal burden [colony-forming units (CFU)], the levels of cytokines (IL-4, IL-8, and IL-17), the levels of oxidative stress markers in rat serum [malondialdehyde (MDA) and superoxide dismutase (SOD)], and histopathology were assessed. MCS was associated with a dose-dependent reduction in fungal burden, with 1.0% MCS achieving CFU reductions comparable to those of nystatin and fenticonazole. Significant decreases in IL-8 and IL-17 and a moderate reduction in IL-4 were detected in rat vaginal lavage fluid, indicating an anti-inflammatory shift. Histopathological examination indicated qualitative differences in epithelial architecture and inflammatory cell distribution in the 0.5% and 1.0% MCS groups; however, inflammation scores did not reach statistical significance. Serum oxidative stress analysis revealed trends toward lower MDA levels and higher SOD activity, but the differences were not statistically significant. These findings suggest that MCS is a promising nonanimal-derived topical antifungal agent with both antifungal and immunomodulatory potential, warranting further clinical investigation.

Keywords:   Candida spp.; Antifungal activity; Microbial chondroitin sulfate; Vaginal candidiasis

DOI:  https://doi.org/10.1038/s41598-026-49469-0
ACS Omega. 2026 Apr 07. 11(13): 20509-20519

Chemically Engineered Sulfates of Lasiodiplodan: Antioxidant, Antimicrobial, and Antirespiratory Syncytial Virus (RSV) Activities.

Alaor Martins da Silva, André Luiz Dyna, Tamires Pereira Rosa, Gabrielle Cristina Calegari, Alexandre Orsato, Aneli M Barbosa-Dekker, Robert F H Dekker, Ligia Carla Faccin-Galhardi, Mário Antônio Alves da Cunha.

β-Glucans are carbohydrate macromolecules with significant clinical and biotechnological applications, whose biological properties are enhanced through chemical modifications, such as sulfation. This study aimed to chemically engineer sulfated derivatives of the (1→6)-β-d-glucan lasiodiplodan and to evaluate how different degrees of sulfation influence its antioxidant, antimicrobial, and antiviral activities. The chemically engineered sulfated derivatives LAS-S1 (DS 0.11) and LAS-S2 (DS 0.51) were synthesized using the sulfating agent chlorosulfonic acid, with different solvents: N,N-dimethylformamide (solvent/stabilizer) and pyridine (proton-neutralizing agent). Sulfation improved the solubility and enhanced the biological activities of both derivatives. LAS-S2 demonstrated better antimicrobial and antiviral activity than LAS-S1. Sulfation was shown to contribute to ·OH and H2O2 scavenging activity, with a dose-dependent effect related to both the concentration of the sulfated compound and its degree of sulfation. The fungistatic and bacteriostatic effects were demonstrated against Escherichia coli, Listeria monocytogenes, Salmonella enterica Typhimurium, Candida albicans, and Candida tropicalis. LAS-S2 exhibited potent inhibition of respiratory syncytial virus (RSV) in vitro, with a high selectivity index (>724.63), and interfered with multiple stages of viral replication. These findings highlight sulfation as an effective strategy to enhance the biological functions of lasiodiplodan. LAS-S2 emerges as a safe (noncytotoxic) and promising candidate for biotechnological and pharmaceutical applications, including novel antimicrobial and antiviral treatments. Future studies should focus on elucidating structure-activity relationships, optimizing sulfation patterns, and evaluating the in vivo efficacy and pharmacological properties of sulfated lasiodiplodan derivatives.

DOI: https://doi.org/10.1021/acsomega.5c11984
J Transl Med. 2026 Apr 16.

Low serum dehydroepiandrosterone sulfate is related to diabetic retinopathy in males with type 2 diabetes mellitus.

Shouxia Li, Chaoyu Zhu, Fusong Jiang, Yuanyuan Xiao, Qianqian Wang, Wenjing Song, Qingge Gao, Xinyi Wang, Li Wei.

   OBJECTIVE: Androgens are increasingly recognized as important regulators of metabolic balance and vascular integrity. However, their relationship with diabetic retinopathy (DR) remains incompletely defined and appears to differ by sex. The present study aimed to examine the associations between circulating levels of total testosterone (TT), dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ASD) and DR risk among individuals with type 2 diabetes mellitus (T2DM), with particular emphasis on gender-stratified analyses.
METHODS: This cross-sectional investigation analyzed 796 hospitalized T2DM cases. Serum concentrations of TT, DHEAS, and ASD were quantified using chemiluminescence immunoassays. Multivariable logistic regression was utilized to assess the associations between androgen levels and the presence of DR, with analyses conducted separately for men and women to account for sex-specific differences.
RESULTS: Among male participants, after comprehensive adjustment for potential confounding variables, serum DHEAS levels were independently and inversely linked with DR risk (tertile 3 vs. tertile 1: OR = 0.43, 95% CI: 0.23-0.82; P for trend = 0.007). Restricted cubic spline modeling demonstrated an approximately linear inverse dose-response relationship between DHEAS concentrations and DR risk (overall P < 0.001; nonlinear P = 0.193). No correlations were found between serum TT or ASD levels and DR in men. In female patients, an inverse relationship between TT and DR was attenuated and rendered nonsignificant after full multivariable adjustment, and neither DHEAS nor ASD showed a statistically significant association with DR risk.
CONCLUSIONS: Lower serum DHEAS concentrations are independently linked with elevated DR risk in males with T2DM, suggesting a potential role for DHEAS in the pathophysiology of DR in males.

Keywords:  Androgen; Androstenedione; Dehydroepiandrosterone sulfate; Total testosterone; Type 2 diabetic retinopathy

DOI:  https://doi.org/10.1186/s12967-026-08121-1
3 Biotech. 2026 May;16(5): 161

6-O-Sulfated glycopolymer promotes osteogenesis by amplifying BMP-2 signaling via specific upregulation of BMP receptors.

Zhujie Xu, Yi Liu, Jingxiao Chen, Aiguo Gao, Youjia Xu.

  Bone defect healing failure and osteoporosis pose significant challenges to clinical orthopedics and geriatric medicine, while the structural heterogeneity of natural heparan sulfate (HS) hinders the clarification of the functional role of 6-O-sulfation patterns in osteogenesis and its translational application. To address this gap, we developed a structurally defined 6-O-sulfated heparan sulfate glycopolymer (6-O-HS) via reversible addition-fragmentation chain transfer (RAFT) polymerization and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry, establishing an engineering-based synthesis strategy with controllable molecular weight and uniform structure. In vitro experiments showed that 6-O-HS (5 µg/mL) significantly enhanced alkaline phosphatase (ALP) activity, osteocalcin (OC) expression, and extracellular matrix mineralization in murine bone marrow mesenchymal stem cells (BMSCs), outperforming conventional HS. RNA sequencing and functional validation revealed that 6-O-HS specifically activated the TGF-β/BMP signaling pathway by upregulating the gene and protein levels of BMP receptors (BMPR1A, BMPR1B, BMPR2) without altering BMP-2 ligand expression. In an ovariectomized (OVX) mouse model, 6-O-HS administration significantly improved bone microarchitecture, increased cortical thickness (Ct.Th) and bone volume fraction (BV/TV), and reduced trabecular separation (Tb.Sp). This study presents a reproducible glycopolymer synthesis and application framework, integrating precision chemical engineering, in vitro mechanistic verification, and in vivo efficacy validation. The framework provides a low-cost, scalable engineering tool for targeted regulation of BMSC osteogenic differentiation, offering novel solutions for bone tissue engineering scaffold development and osteoporosis treatment with broad translational potential in regenerative medicine.
Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-026-04787-y.

Keywords:  BMP-2; Heparan sulfate; Osteogenesis; Receptor; Sulfation

DOI:  https://doi.org/10.1007/s13205-026-04787-y
J Clin Med. 2026 Apr 07. pii: 2772. [Epub ahead of print]15(7):

Diagnostic Utility of ACTH, Cortisol, DHEAS, and Their Derived Ratios in Cushing's Syndrome Subtypes.

Ekin Yiğit Köroğlu, Abbas Ali Tam, Sevgül Faki, Pervin Demir, Fatma Neslihan Çuhaci Seyrek, Didem Özdemir, Oya Topaloğlu, Reyhan Ersoy, Bekir Çakir.

  Background/Objectives: Differentiating Cushing's disease (CD) from adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (AICS) remains challenging in patients with equivocal ACTH levels. While dynamic testing is frequently required, baseline hormonal measurements may offer a simpler diagnostic approach. We aim to evaluate the diagnostic value of baseline plasma ACTH, cortisol, and dehydroepiandrosterone sulfate (DHEAS) levels and their derived ratios for differentiation between ACTH-dependent and ACTH-independent Cushing's syndrome, and to propose a diagnostic algorithm based on these parameters. Methods: This retrospective single-centre study included adult patients with endogenous Cushing's syndrome aged 18-75 years who were followed at our institution. Patients with ectopic/paraneoplastic Cushing's syndrome were excluded. The AICS group comprised overt adrenal CS and mild autonomous cortisol secretion cases. Morning baseline plasma ACTH (pg/mL), serum cortisol (µg/dL), and serum DHEAS (µg/dL) levels were measured and ratios calculated: cortisol-to-ACTH ratio (CAR), DHEAS-to-cortisol ratio (DCR), and CAR-to-DHEAS ratio (CAR/D). ROC analysis assessed diagnostic performance with age and sex adjustments. Results: A total of 100 patients were included, comprising 43 patients with CD and 57 with AICS. Plasma ACTH demonstrated high diagnostic accuracy for identifying CD with a cut-off of ≥14.65 pg/mL (sensitivity 100%, specificity 98.25%, AUC 0.998). Serum DHEAS showed strong discriminative power with a cut-off of ≥67.15 µg/dL (sensitivity 88.37%, specificity 91.23%, AUC 0.925), achieving high discriminative power after age-sex adjustment at ≥85.59 µg/dL (sensitivity 100%, specificity 100%, AUC 0.999). CAR showed good performance in identifying CD with a cut-off of ≤0.75 µg/dL per pg/mL (sensitivity 93.02%, specificity 98.25%, AUC 0.980). CAR/D demonstrated high diagnostic power with a cut-off of ≤1.54 (sensitivity 95.35%, specificity 98.25%, AUC 0.974), improving after age-sex adjustment to ≤2.36 (sensitivity 97.87%, specificity 96.23%, AUC 0.992). Conclusions: Baseline plasma ACTH, serum cortisol, and serum DHEAS measurements, along with derived ratios-especially CAR and CAR/D-provide highly accurate differentiation between ACTH-dependent and ACTH-independent Cushing's syndrome. These widely available measurements may reduce dependence on dynamic testing and improve diagnostic accuracy in patients with equivocal findings.

Keywords:  Cushing’s disease; Cushing’s syndrome; adrenocorticotropic hormone; cortisol; dehydroepiandrosterone sulfate; mild autonomous cortisol secretion

DOI:  https://doi.org/10.3390/jcm15072772
Plants (Basel). 2026 Apr 04. pii: 1115. [Epub ahead of print]15(7):

Evolutionary and Transcriptomic Analyses of the Plant TPST-Sulfated Peptides System, with Insights from Woody Liriodendron chinense.

Yu Liu, Kaiyue Hong, Teja Manda, Xiangyang Hu, Liming Yang.

  Sulfated peptides, such as PSK, PSY, CIF, and RGF, are crucial regulators of plant growth, development, and stress responses, with their activity dependent on post-translational tyrosine sulfation by tyrosylprotein sulfotransferase (TPST). This study explores the evolutionary history and the interaction mechanisms between TPST and sulfated peptides in plants. Systematic analyses of multi-species genomes show that TPST can be traced back to the chlorophyte lineage, whereas PSK, a sulfated peptide, appears to have emerged in gymnosperms. TPST is evolutionarily conserved, typically present in low copy numbers across plant lineages, while its peptide substrates have expanded in angiosperms. In Liriodendron chinense, TPST-sulfated peptide gene promoters are enriched with cis-regulatory elements linked to abscisic acid, gibberellin responsiveness, and anaerobic induction. Synteny analyses revealed collinearity between sulfated peptide genes in L. chinense, Magnolia biondii, Arabidopsis thaliana, and Populus trichocarpa, but not with Oryza sativa. Molecular docking identified key TPST-PSK interaction sites in the sulfotransferase domain, with several critical residues facilitating binding. Transcriptomic and co-expression network analyses revealed that LcTPST was expressed at lower levels than its peptide precursor genes, while LcPSK2 remained highly expressed after the torpedo stage of somatic embryogenesis. Stress conditions significantly increased PSK-associated module connectivity, enriched in transcription factors such as WRKY, bHLH, bZIP, and MADS. This study provides insights into the evolutionary, structural, and regulatory aspects of the TPST-sulfated peptide system in plants.

Keywords:  molecular docking; phylogenetic analysis; sulfated peptides; transcriptional regulation; tyrosylprotein sulfotransferase (TPST)

DOI:  https://doi.org/10.3390/plants15071115
Nat Commun. 2026 Apr 15.

Dynamic structures of dengue virus serotype 2 secreted NS1 and their interactions with heparan sulfate.

Qunfei Zhou, Thiam-Seng Ng, G Suthershinii, Aaron Wai Kit Tan, Victor A Kostyuchenko, Guntur Fibriansah, Shee-Mei Lok.

Dengue secreted non-structural protein 1 (sNS1) contributes to the vascular permeability symptom of severe dengue hemorrhagic fever. Previous flavivirus sNS1 structures suggest that they predominantly exist as loose tetramers. Here, we report two stable tetramer structures (3.1-3.6 Å) together with loose tetramers. Formation of the stable tetramers involves a dramatic rearrangement of their N-terminal regions compared to the loose tetramers. We observe a higher molecular weight complex (HMWC) comprising dimeric sNS1 and heat shock proteins, which exhibits much lower endothelial hyperpermeability activity than the tetramer-enriched samples. We also determine high-resolution structures of the sNS1 complex with heparin, an analogue of the attachment factor heparan sulfate, showing that heparin binds to a conserved basic groove on the outer surface of the dimer, at the intra-dimer interface. Pre-incubation of sNS1 with heparin reduces its endothelial hyperpermeability activity. Our findings provide important structural information for future sNS1-based drug or vaccine design.

DOI: https://doi.org/10.1038/s41467-026-71970-3
Int J Biol Macromol. 2026 Apr 14. pii: S0141-8130(26)01950-1. [Epub ahead of print] 152024

A low-cost disposable label-free immunosensor for high-performance detection of indoxyl sulfate using chitosan based tertiary nanocomposite.

Archana, Payal Rana, Anupam Teotia, Rajeev Singh, Saran Kumar, Pratima R Solanki, Anil Kumar.

  Indoxyl sulfate (IS) is a gut microbiota derived metabolite having various adverse implications in chronic kidney disease, cardiovascular disease, uremic syndrome. IS is also known as protein bound uremic toxin. Due to the serious issues caused by IS its timely quantification is important for the diagnosis and prevention of several diseases. Several traditional methods are available for detecting IS, including mass spectrometry and liquid chromatography. However, as these techniques are both time-consuming and costly our work represents the first demonstration of an electrochemical immunosensor for detecting IS using an anti-IS monoclonal antibody. The screen-printed carbon electrode (SPCE) was modified with a tertiary nanocomposite of chitosan-Au nanoparticles-CeO2 nanoparticles to provide abundant chemical groups through chitosan for the immobilization of antibodies and to deliver the synergistic effects of the Au-CeO2 nanocomposite such as improved surface area to volume ratio, electrical conductivity, and biocompatibility. The detection of IS using the fabricated label-free sensor was performed using the cyclic voltammetry technique. The fabricated sensor showed the sensitivity of 22.8 μA log10 (μM) cm-2 and LOD of 0.06 μM in the linear range of 1 nM to 1000 μM. The selectivity test was also performed on this immunosensor in the presence of various possible interference molecules found in human urine. The performance of the fabricated sensor was also assessed using a spiked urine sample, showing an acceptable recovery rate of 92.54-107.27%.

Keywords:  Chitosan; Immunosensor; Indoxyl sulfate

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.152024
Biochem Biophys Rep. 2026 Jun;46 102569

Quantification of glycosaminoglycans in dried blood spots, and evaluation of its usefulness as a secondary newborn screening test for mucopolysaccharidoses.

Wataru Oboshi, Asami Hirakiyama, Masahiro Miura, Hikaru Omachi, Misa Tanaka, Joo-Hyun Seo, Akira Ohtake, Yoshimitsu Osawa, Mika Ishige, Motomichi Kosuga, Takeshi Munenaga, Ohsuke Migita, Hiromi Nyuzuki, Hideo Sasai, Tokiko Fukuda, Shinichiro Sano, Tetsuya Ito, Ryosuke Bo, Yasuhiro Takeshima, Hiroyuki Esaki, Takahito Inoue, Shinichiro Nagamitsu, Yoriko Watanabe, Kimitoshi Nakamura, Hirotake Sawada, Shinsuke Maruyama, Kei Murayama, Torayuki Okuyama.

  Mucopolysaccharidoses (MPS) are a group of lysosomal disorders characterized by pathological accumulation of glycosaminoglycans (GAGs). Enzyme-based newborn screening (NBS) for MPS often yields high false-positive rates because of carriers and pseudodeficient newborns. To improve screening specificity, we developed an LC-MS/MS-based enzymatic method to quantify GAG-derived disaccharides in dried blood spots (DBSs) and evaluated its utility as a second-tier test. Using DBS samples MPS-positive newborns, we quantified dermatan sulfate- (DS), heparan sulfate- (HS), and keratan sulfate-derived disaccharides. Under the primary positivity rule (DS or HS ≥ the 95th percentile cutoff), the method achieved 100% sensitivity and specificity for MPS I, completely eliminating false-positive results among MPS I carriers. For MPS II, the same rule yielded 100% sensitivity and 84.3% specificity. Reanalysis using a stricter rule requiring both DS and HS to exceed the cutoff improved specificity for MPS II to 100% without loss of sensitivity (100%). All confirmed MPS I and II patients exceeded both DS and HS cutoffs, whereas HS-only values above the cutoff occurred exclusively in MPS II pseudodeficiency, reflecting analytical and cutoff-related overlap rather than pathological GAG accumulation. Based on these findings, we recommend the stricter dual-marker rule for laboratory implementation, particularly for improving specificity in MPS II. Implementation of this approach as a second-tier test may substantially reduce false-positive referrals, eliminating all false positives for MPS I carriers and improving specificity for MPS II pseudodeficiency from 84.3% to 100%. This method may serve as a practical complementary screening tool within expanded NBS programs.

Keywords:  Dermatan sulfate; Glycosaminoglycan; Heparan sulfate; Keratan sulfate; Mucopolysaccharidosis; Newborn screening

DOI:  https://doi.org/10.1016/j.bbrep.2026.102569
JCEM Case Rep. 2026 Apr;4(4): luag059

Severe hyperandrogenism and mild autonomous cortisol secretion from a functional lipid-poor adrenal cortical adenoma.

Elio Monsour, Prerna Dogra, Stephanie Giparas, William H Westra, Rachel Voss, Colleen Veloski.

  A 44-year-old woman presented with progressive hirsutism, deepening of voice, irregular menses, and left flank discomfort. Laboratory evaluation revealed markedly elevated serum testosterone and androstenedione levels, along with unsuppressed cortisol following an overnight 1 mg dexamethasone test. Notably, dehydroepiandrosterone sulfate (DHEA-S) levels remained within normal limits. Imaging identified a 4.2-cm heterogeneously enhancing left adrenal mass with a precontrast attenuation of 15 Hounsfield units, consistent with a lipid-poor lesion. 18F-fluorodeoxyglucose positron emission tomography-computed tomography demonstrated intensely avid uptake. Open adrenalectomy was performed, and final pathology confirmed a benign adrenocortical adenoma. Postoperatively, both testosterone and androstenedione levels normalized. The patient received temporary hydrocortisone replacement per our institution's protocol for treatment of presumed postoperative adrenal insufficiency, which was discontinued after biochemical recovery of endogenous cortisol production. This case highlights that not all androgen and cortisol co-secreting adrenal masses are malignant, and that preoperative normal DHEA-S levels do not exclude an underlying adrenal source of hyperandrogenism.

Keywords:  adrenal mass; adrenalectomy; cortisol secretion; hyperandrogenism; lipid-poor adrenal adenoma

DOI:  https://doi.org/10.1210/jcemcr/luag059
Arch Pharm (Weinheim). 2026 Apr;359(4): e70239

Fully Synthetic Non-Carbohydrate Heparin Mimetics-Perspectives for Therapeutic Anticoagulation and Beyond?

Katrin Nekipelov, Vito Ferro, Gerd Bendas.

  Heparin is one of the oldest drugs on the market. Although clinically well established as an anticoagulant for decades, owing to its natural origin and heterogeneous glycosaminoglycan polysaccharide structure, ensuring consistent quality and reproducible biological activity remains challenging. While these facts argue against future applications of heparin in clinical routine, an increasing number of studies reveal additional potential therapeutic applications of heparin beyond its anticoagulant efficacy, that is, as an antiviral strategy or as a multi-targeted approach in oncology. Therefore, heparin appears to be a structural template for pleiotropic compounds. To combine the beneficial pleiotropic properties of heparin with improved reproducibility and safety, fully synthetic heparin mimetic substances have increasingly become a focus of scientific research. These studies enable more detailed structure-activity relationships of heparin in its interaction with proteins or diseases to be elucidated, thereby facilitating the development of novel compounds for potential therapeutic use. This review focuses in particular on fully synthetic non-carbohydrate heparin mimetic polymers with anticoagulant activities, as well as their properties beyond anticoagulation. Advances in the development of such mimetics, especially over the past decade, allow increasingly robust conclusions to be drawn regarding their efficacy and contribute to a deeper understanding of this class of compounds.

Keywords:  Heparin; Heparin mimetics; anticoagulation; synthetic polymers

DOI:  https://doi.org/10.1002/ardp.70239
Int J Mol Sci. 2026 Mar 25. pii: 2997. [Epub ahead of print]27(7):

miR-4516-Loaded Engineered Milk Extracellular Vesicles Attenuate Indoxyl Sulfate-Induced Mitochondrial Dysfunction and Improve Renal Function in a CKD Mouse Model.

Jeongkun Lee, Jun Young Yoon, Jae Young Lee, Sang Hun Lee.

  Chronic kidney disease (CKD) involves uremic toxin-driven tubular injury and systemic vascular dysfunction, in which mitochondrial impairment and apoptotic cell loss contribute to progressive tissue deterioration. Accordingly, a targeted EV platform is required to enable efficient miRNA delivery to the toxin-stressed tubular-endothelial compartment. Based on our previous study showing that melatonin restores miR-4516 levels under CKD-related stress, we directly loaded miR-4516 into engineered extracellular vesicles (EVs) to evaluate its effects on mitochondrial function and cell survival. Here, we engineered EVs with a G3-C12/RGD surface modification and established a miR-4516 loading strategy to enhance delivery to kidney proximal tubule cells and vascular endothelial cells. miR-4516 loading increased EV-associated miR-4516 levels without major changes in particle size distribution, and EV identity was supported by CD9 and CD81 expression. Confocal microscopy and flow cytometry demonstrated increased cellular uptake of miR-4516-loaded G3-C12/RGD-EVs compared with control EVs in TH1 proximal tubule cells and HUVECs. Under indoxyl sulfate stress, engineered EV treatment restored intracellular miR-4516 and improved mitochondrial function, as indicated by recovery of respiratory Complex I and Complex IV activities and improved Seahorse bioenergetic parameters (OCR/ECAR, basal and maximal respiration, ATP-linked respiration, and spare respiratory capacity). Annexin V staining further indicated reduced toxin-induced apoptosis. In an adenine diet-induced CKD mouse model, intravenous administration of miR-4516-loaded G3-C12/RGD-EVs improved urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine. These findings indicate that miR-4516-loaded, targeting-engineered EVs may mitigate uremic toxin-associated mitochondrial dysfunction and renal impairment in CKD.

Keywords:  chronic kidney disease; indoxyl sulfate; miR-4516; milk-derived extracellular vesicles; mitochondrial dysfunction

DOI:  https://doi.org/10.3390/ijms27072997
J Pediatr Endocrinol Metab. 2026 Apr 14.

Effect of androgens on retinal microvasculature in prepubertal girls with isolated premature pubarche.

Gamze Karataş, Derya Çepni Çakır, Aslı Kırmacı Kabakcı, Mehmet Egemen Karataş, Diğdem Bezen, Dilan Yıldız, Akın Çakır.

   OBJECTIVES: To evaluate the effect of androgens on retinal microvasculature in prepubertal girls with isolated premature pubarche (PP) with optical coherence tomography (OCT) and OCT angiography (OCTA).
METHODS: Eighty-six prepubertal, non-obese girls with isolated PP with normal birth weight and 86 age-matched control girls were evaluated. Retinal microvascular structures in the macular and optic disc regions were examined using OCT and OCTA. Data from subjects with isolated PP were compared with data from healthy controls. Correlations between dehydroepiandrosterone sulfate (DHEA-S), androstenedione (AS), testosterone, 17-hydroxyprogesterone (17-OHP) levels, bone age, pubertal stage as well as OCT and OCTA parameters were evaluated.
RESULTS: The inferior retinal nerve fiber layer (RNFL) thickness in the isolated PP group was significantly higher than the control group (p=0.007). A statistically significant increase in the vessel density (VD) was observed in temporal quadrant of the superficial capillary plexus (SCP) and inferior quadrant of the deep capillary plexus (DCP) in the isolated PP group compared with the control group (p<0.05). There were significant positive correlations between DHEAS, AS, testosterone levels and RNFL, macula-disk regions's OCTA parameters (p<0.05).
CONCLUSIONS: In the isolated PP patients, thickening of RNFL and increased VD in the macula and optic disc region were recognized under the effect of androgens compared to the control group. In these patients, early microvascular changes can be detected noninvasively by means of OCT and OCTA. These findings suggest a potential link between androgen exposure and retinal microvascular alterations; however, further studies are needed to explore their clinical implications.

Keywords:  androgen; deep capillary plexus; retinal nerve fiber layer; superficial capillary plexus; vessel density

DOI:  https://doi.org/10.1515/jpem-2025-0685