bims-supasi 2026-03-29 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–03–29
twelve papers selected by
Jonathan Wolf Mueller, University of Birmingham

Marine sulfated glycan inhibits tau-heparan sulfate interaction and tau cellular uptake.
Carbohydrate sulfotransferases in humans: Repertoire and regulation of glycan-lectin interactions.
Change in the chondroitin/dermatan structure in distal lung tissue from COPD patients.
Influence of Propolis-Containing Nonwoven PLGA Dressings on Dermatan and Chondroitin Sulfate Dynamics During Burn-Wound Healing.
Green synthesis of chitosan sulfate using deep eutectic solvent and its application in wound healing.
Functional dissection of the prototype foamy virus glycoprotein heparan sulfate binding site.
Heparin-Based Biomaterials for Sustained Release of Growth Factors for Bone Tissue Engineering and Regeneration.
Delivery growth factors by layer-by-layer assembly in nanofibers for enhancing bone defect repairment along with neurogenesis.
Non-clinical safety of novel cross-linked chondroitin sulfate (SI-449) as an anti-adhesion barrier for abdominal and pelvic surgeries.
Serum dehydroepiandrosterone sulfate and asthma in a nationwide study of U.S. adults.
Synthesis of Sulfated Glycomimetics with Micromolar Affinity for Midkine.
Steroid/thyroid hormones and inflammatory markers in adolescents with ADHD: comparisons with healthy controls and modifications by methylphenidate.

Int J Biol Macromol. 2026 Mar 23. pii: S0141-8130(26)01518-7. [Epub ahead of print] 151592

Marine sulfated glycan inhibits tau-heparan sulfate interaction and tau cellular uptake.

Kristina Jones, Alexandre Pennell, Peng He, James Gibson, Fuming Zhang, Vitor H Pomin, Chunyu Wang.

  Heparan sulfate (HS) proteoglycans mediate the cellular uptake of tau, a critical step in the prion-like spread of tau pathology in Alzheimer's disease. In this study, we tested if several marine sulfated glycan of diverse structures can inhibit the tau-HS interaction. Through experiments of SPR we found that marine-derived sulfated fucans bind tau with similar affinity to heparin, whereas fucosylated chondroitin sulfates (FucCS) from several holothurian species bind tau with substantially higher affinity. Using solution NMR, we further characterized FucCS-tau interactions with residue-level resolution, revealing complex binding behavior distinct from heparin-tau binding. A high-affinity site is observed as peak intensity loss spanning the middle of PRR2 through R' of tau at low FucCS concentration, whereas another weaker binding site is characterized by both chemical shift perturbation and gradual peak intensity attenuation from the end of N2 through the middle of PRR2. Finally, we demonstrated that FucCSs inhibit tau uptake in SH-SY5Y cells with an IC50 of 130 μg/mL, shown by both confocal microscopy and flow cytometry. Together, these findings have identified marine-derived polysaccharides as promising candidates for therapeutic development targeting tau-HS interactions.

Keywords:  Alzheimer's disease; Fucosylated chondroitin sulfate; Heparan sulfate; Marine sulfated glycans; Sulfated fucans; Tau

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.151592
Biochim Biophys Acta Gen Subj. 2026 Mar 21. pii: S0304-4165(26)00035-8. [Epub ahead of print]1870(6): 130935

Carbohydrate sulfotransferases in humans: Repertoire and regulation of glycan-lectin interactions.

Kim Wai Parn, Takashi Angata.

   BACKGROUND: Sulfate in glycans often serves as a determinant of glycan-protein interactions underlying mammalian physiology. Sulfated glycoconjugates in mammals encompass proteoglycans, glycoproteins, and glycolipids, and more than 30 sulfotransferases catalyze carbohydrate sulfation.
SCOPE OF REVIEW: We summarize the repertoire of carbohydrate sulfotransferases in humans and their relevance to human physiology, focusing on those that modify N- and O-glycans on glycoproteins and modulate glycan-protein interactions.
MAJOR CONCLUSIONS: Sulfate is indispensable in some glycan-protein interactions, whereas sialic acid can replace it in some others. The presence of both sulfate and sialic acid enhances some interactions. Regulation of glycan-protein interactions by the combination of sulfate and sialic acid has been actively investigated, while in vivo proof of such interactions may still be limited, particularly for those discovered recently.
GENERAL SIGNIFICANCE: A deeper understanding of glycan-protein interactions regulated by sulfation will advance our understanding of human physiology and contribute to improving human health.

Keywords:  Biomarkers; Carbohydrate sulfotransferase; Lectins; Sialic acid; Sulfate

DOI:  https://doi.org/10.1016/j.bbagen.2026.130935
Sci Rep. 2026 Mar 23. pii: 9721. [Epub ahead of print]16(1):

Change in the chondroitin/dermatan structure in distal lung tissue from COPD patients.

Hani N Alsafadi, Annika Nybom, Darcy Wagner, Anders Malmström, Sandra Lindstedt, Leif Bjermer, Göran Dellgren, Johan Malmström, Emil Tykesson, Gunilla Westergren-Thorsson, Oskar Hallgren.

  Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airway remodeling, including emphysema and fibrosis. Proteoglycans and their glycosaminoglycan (GAG) chains are key components of the extracellular matrix and may be altered as the disease advances. This study analyzed lung tissue from COPD patients (GOLD stages II-III and IV), non-COPD smokers, and non-smokers to assess proteoglycan and GAG changes. While LC-MS revealed no alterations in chondroitin/dermatan sulfate (CS/DS) or heparan sulfate (HS) proteoglycan core proteins, the total GAG level increased in GOLD II-IV patients. HS displayed increased N- and 2-O-sulfation in GOLD IV, while CS/DS levels and 4-O-sulfation were enhanced across GOLD II-IV. These findings were supported by transcriptomic data indicating upregulation of CHST11, the main CS/DS 4-O-sulfotransferase. In line with previous findings, TGF-β signaling was shown to be enriched in COPD patients and to regulate the CHST11 expression. These results were confirmed by TGF-β stimulation of lung fibroblasts showing increased CS/DS levels, 4-O-sulfation, and CHST11 expression. In conclusion, COPD is associated with disease-stage-specific changes in GAG sulfation, particularly enhanced CS/DS 4-O-sulfation that is likely to be driven by TGF-β. These alterations may contribute to extracellular matrix remodeling and represent potential targets for therapeutic intervention to mitigate disease progression.

Keywords:  Chondroitin/dermatan sulfate; Chronic obstructive pulmonary disease; Glycosaminoglycans; Heparan sulfate; Proteoglycans; Transforming growth factor-β

DOI:  https://doi.org/10.1038/s41598-026-44120-4
Pharmaceuticals (Basel). 2026 Feb 27. pii: 383. [Epub ahead of print]19(3):

Influence of Propolis-Containing Nonwoven PLGA Dressings on Dermatan and Chondroitin Sulfate Dynamics During Burn-Wound Healing.

Kinga Orlińska, Mateusz Stojko, Jakub Włodarczyk, Janusz Kasperczyk, Oskan Tasinov, Diana Ivanova, Mladena Nikolaeva Radeva, Paweł Janik, Katarzyna Komosińska-Vassev, Krystyna Olczyk, Jerzy Stojko, Paweł Olczyk.

  Background/Objectives: Burn wounds are complex injuries associated with extensive inflammation, extracellular matrix (ECM) damage, and a high risk of impaired tissue remodeling and scarring. Modern wound dressings are expected not only to protect the wound bed but also to actively support the healing process. Biodegradable polymer-based nonwoven dressings incorporating natural bioactive compounds, such as propolis, may favorably influence wound repair. The aim of this study was to evaluate the effect of propolis-containing biodegradable, nonwoven poly(lactide-co-glycolide) (PLGA) dressings on the dynamics of dermatan sulfate and chondroitin sulfate content during burn-wound healing. Methods: The present study investigated temporal alterations in sulfated glycosaminoglycans (GAGs), including dermatan and chondroitin sulfates, during the healing of experimentally induced burn wounds in white domestic pigs treated with biodegradable, nonwoven poly(lactide-co-glycolide) (PLGA) dressings containing 5 wt% or 10 wt% of propolis. Control tissue samples were obtained from wounds treated with physiological saline or nonwoven PLGA dressings without propolis. Quantitative analysis of GAG content was performed on days 0, 3, 5, 10, 15, and 21 of the healing process using enzyme-linked immunosorbent assay (ELISA). Statistical differences between groups were assessed by one-way multivariate analysis of variance (MANOVA) followed by Tukey's post hoc test. Results: Propolis-containing biodegradable nonwoven PLGA dressings significantly increased dermatan sulfate and chondroitin sulfate content in the burn wound bed compared to control treatments. The effect was observed at multiple time points and was more pronounced for dressings containing 10 wt% of propolis than for those containing 5 wt%. Conclusions: Biodegradable nonwoven PLGA dressings incorporating propolis modulate glycosaminoglycan dynamics during burn-wound healing, indicating enhanced extracellular matrix remodeling and supporting their potential use as bioactive burn wound dressings.

Keywords:  burns; chondroitin sulfates; dermatan sulfates; glycosaminoglycans; nonwoven PLGA; propolis; wound healing

DOI:  https://doi.org/10.3390/ph19030383
Int J Biol Macromol. 2026 Mar 23. pii: S0141-8130(26)01525-4. [Epub ahead of print]357 151599

Green synthesis of chitosan sulfate using deep eutectic solvent and its application in wound healing.

Jing Zhang, Yiming Chen, Wenya Meng, Huifang Liu, Jing Li, Long Yu, Ping Dong.

  The biomedical potential of chitosan (CS) in wound healing is constrained by poor solubility and processability. Herein, we report a green and efficient route to synthesize water-soluble sulfated chitosan (SCS) with controlled sulfation patterns, using a sulfamic acid-urea deep eutectic solvent (DES). Comprehensive characterization (FTIR, 13C and HSQC NMR, HPSEC-MALLS-RI, and elemental analysis) verified tunable sulfation and molecular weights, with zeta potential further delineating the corresponding surface properties. Biological evaluations demonstrated that SCS possesses excellent biocompatibility, promotes cell migration, enhances TGF-β1/VEGF secretion, and facilitates angiogenesis, collagen deposition, and extracellular matrix remodeling. Structure-activity analysis revealed sulfation patterns determined bioactivity, with 6-O-sulfated SCS demonstrating superior wound closure rates (96.2% in 6-O-SCS vs. 88.6% in control group on 12 day post-treatment). This study provides a sustainable approach to SCS production and highlights its therapeutic potential in wound management.

Keywords:  Chitosan sulfate; Deep eutectic solvent; Wound healing

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.151599
Retrovirology. 2026 Mar 21.

Functional dissection of the prototype foamy virus glycoprotein heparan sulfate binding site.

Max Büttrich, Nicole Stanke-Scheffler, Thomas Calcraft, Peter B Rosenthal, Dirk Lindemann.

   BACKGROUND: The foamy virus (FV) glycoprotein complex (GPC) facilitates exceptionally broad species and tissue tropism. While cell surface heparan sulfate (HS) serves as a known attachment factor, it is not essential for viral entry. Recent high-resolution structures of GPCs from various FV species identified an evolutionarily conserved, positively charged surface patch (PCSP) on the receptor-binding domain (RBD) as a putative HS-binding site (HSBS). To date, only the gorilla FV (SFVggo) HSBS has been functionally characterized, demonstrating the role of basic PCSP residues in HS-dependent attachment. Experimental evidence supporting a universal role for the GPC PCSP across other FV species is currently lacking.
RESULTS: The prototype FV (PFV) GPC PCSP consists of four central residues surrounded by five peripheral, positively charged residues. Using charge-switch mutagenesis, we investigated the functional role of eight PCSP residues. The central residues-K343, K355, R357, and K368-proved essential for HS-dependent attachment and infection across various target cells. Individual mutations of these residues reduced attachment and infectivity in HT1080 cells by 50- to 100-fold. Among peripheral residues, only K356 contributed significantly to these processes on different HS-expressing target cells. Notably, all mutant PFV GPCs maintained levels of attachment and infectivity in HS-deficient cells similar to those of the wild-type, though these levels were 10- to 30-fold lower than in HS-expressing parental cells but well above background.
CONCLUSIONS: The minimal HSBS of the PFV GPC is defined by four central, evolutionarily conserved positively charged residues. Substituting these with negatively charged amino acids abolishes HS-dependent attachment and severely reduces specific infectivity. The minor impact of the peripheral residue mutation K356E, combined with the lack of evolutionary conservation among most peripheral positively charged residues in primate FV species, suggests these residues play only a secondary role in HS interaction. Furthermore, the residual infectivity of PCSP mutants in HS-deficient cells confirms that HS is an important attachment factor but not an essential entry receptor. The functional homology between PFV and SFVggo GPCs strongly suggests that this conserved PCSP constitutes a universal HS-binding site across all FV species.

Keywords:  Attachment factor; Binding site; Foamy virus; Glycoprotein; Heparan sulfate

DOI:  https://doi.org/10.1186/s12977-026-00676-7
J Funct Biomater. 2026 Mar 22. pii: 156. [Epub ahead of print]17(3):

Heparin-Based Biomaterials for Sustained Release of Growth Factors for Bone Tissue Engineering and Regeneration.

Keisuke Nakayama, Xueqin Gao, Britney S Force, Marc J Philippon, Johnny Huard.

  Large bone defects resulting from trauma, tumor resection, infection, or degenerative diseases pose a major clinical challenge in orthopedic surgery and regenerative medicine. Despite advances in biomaterials and surgical techniques, successful outcomes are often compromised by poor vascularization, limited osteoinduction, and donor-site morbidity associated with autografts or allografts. However, conventional delivery systems suffer from burst release, rapid clearance, off-target effects, and supraphysiologic dosing, which can lead to undesirable complications such as ectopic ossification and inflammation, with some reports raising concerns about the long-term tumorigenic risk. Heparin, a naturally highly sulfated glycosaminoglycan structurally related to heparan sulfate, has emerged as a particularly attractive candidate for affinity-based biomaterial systems. It naturally binds over 300 growth factors, including bone morphogenetic proteins. By protecting these proteins from enzymatic degradation, enhancing their bioavailability, and mediating receptor clustering, heparin provides both biochemical stability and biofunctional modulation. This review provides a comprehensive overview of heparin-based delivery strategies in bone tissue engineering. We begin by describing the biological functions of heparin in modulating growth factor activity. We then discuss in detail the different heparin-based biomaterials designed to sustain the release of growth factors for bone tissue engineering, including the heparin-polycation coacervate system; heparin-based supramolecules; and heparin-based hydrogels, nanoparticles, and microspheres for sustained release of bone morphogenic proteins and other growth factors for bone tissue engineering. Finally, we assess the clinical and translational relevance of heparin-based systems, identify key challenges, and outline future perspectives, highlighting the potential of these biomaterials for providing safer and more effective therapies for bone regeneration.

Keywords:  bone morphogenetic proteins; bone tissue engineering; heparin; heparin modified hydrogel; heparin modified microsphere; heparin modified nanoparticle; heparin/poly(ethylene argininylaspartate diglyceride) (PEAD) coacervate

DOI:  https://doi.org/10.3390/jfb17030156
Int J Biol Macromol. 2026 Mar 25. pii: S0141-8130(26)01590-4. [Epub ahead of print] 151664

Delivery growth factors by layer-by-layer assembly in nanofibers for enhancing bone defect repairment along with neurogenesis.

Xiaoyan Wang, Shan Huang, Ying Yang, Kunlu Lin, Long Liu, Haoming Liu, Zhenzu Bai, Weijia Zheng, Kai Jiang.

  In our daily life, bone defects with sensory losing caused by limb trauma, degenerative diseases, or tumor resection are very common. When the bone defect size exceeds the critical size, it cannot spontaneously heal. Therefore, clinical intervention and artificial bone materials are needed to repair damaged bone tissue and restore sensation. Here, we reported that Collagen (Col) and Chondroitin sulfate (CS) adsorbed into hydroxyapatite (HA) for long-time sustained release was used to prepare nanofibrous scaffolds (Col+CS)@HA through electrospining, fibroblast growth factor (FGF) and CS + Col as two layers were used to prepare (Col+CS)@HA-(FGF/CS + Col)5 nanofiber scaffold through Layer-by-Layer (LBL) self-assembly technology. Interestingly, we found that neurogenesis could accelerate osteogenesis from RNA sequencing result. To confirm this result, we found that (Col+CS)@HA-(FGF/CS + Col)5 scaffold could promote osteogenesis process in bone mesenchymal stem cells (BMSCs) regulated through extracellular regulated protein kinases 1/2 (Erk1/2) activated runt-related transcription factor 2 (Runx2) pathway. Furthermore, the transcriptional levels of downstream genes associated with osteogenesis were significantly elevated. Intriguingly, we also found that (Col+CS)@HA-(FGF/CS + Col)5 scaffold could boost the differentiation of BMSCs into neurons and promote the transcriptional levels of neuron specific genes. As a result, we observed that new neuron was formed in Haversian canal in mice cranial defects area, which means (Col+CS)@HA-(FGF/CS + Col)5 scaffold could not only promote osteogenesis, but also could enhance neurogenesis. Therefore, we believe this study is promising, as it provides new insights towards the process of bone defect repairment along with sensation restorement.

Keywords:  Layer-by-layer; Nanofibrous scaffolds; Neurogenesis; Osteogenesis

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.151664
J Biomater Appl. 2026 Mar 27. 8853282261432825

Non-clinical safety of novel cross-linked chondroitin sulfate (SI-449) as an anti-adhesion barrier for abdominal and pelvic surgeries.

Ayako Shiraki, Shino Ito, Dai Muramatsu, Tomoki Sasaki, Akira Otsuka, Tomomi Miyahara, Katsuya Takahashi, Keiji Yoshioka, Miki Suehiro.

  Postoperative adhesions result from abnormal tissue repair and most frequently occur in patients following abdominal and pelvic surgeries. Prevention of adhesion formation, including the use of anti-adhesion barriers during surgery, is considered the most effective clinical strategy for postoperative adhesions. However, no commercial product is commonly used worldwide because of its insufficient efficacy, complexity, and difficulty of use. We developed a new anti-adhesion barrier using novel biomaterial (SI-449), a cross-linked chondroitin sulfate, in an easy-to-apply powder form. Our previous study using animal models showed that the anti-adhesion efficacy of SI-449 was superior to that of an existing product. In this study, the safety of SI-449 was evaluated based on the results of systemic toxicity tests in rats after intraperitoneal application and a wound healing test in laparotomized rats to mimic its clinical use in abdominal and pelvic surgeries. In the systemic toxicity test, minimal and transient hematological changes and muscular regeneration in the abdominal wall and ileum were observed and were considered to be related to systemic toxicity or local irritation due to SI-449. However, these findings were within the safety margin and not associated with serious toxicity. Other changes were considered physiological reactions to SI-449 or its degradants. In the wound healing test, SI-449 was found to have no effect on the healing of the incisional abdominal wall. In conclusion, the non-clinical safety of SI-449 was confirmed, and this novel biomaterial is expected to be used as an anti-adhesion barrier in abdominal and pelvic surgeries.

Keywords:  anti-adhesion barrier; chondroitin sulfate; cross-linking technology; medical device; postoperative adhesion

DOI:  https://doi.org/10.1177/08853282261432825
Ann Am Thorac Soc. 2026 Mar 23. pii: aaoag075. [Epub ahead of print]

Serum dehydroepiandrosterone sulfate and asthma in a nationwide study of U.S. adults.

Yueh-Ying Han, Franziska J Rosser, Juan C Celedón.

BACKGROUND: Dehydroepiandrosterone sulfate (DHEA-S) has anti-inflammatory and immune-modulating properties but its role in asthma is unclear.
OBJECTIVE: To examine serum DHEA-S levels and asthma or asthma exacerbations in a nationwide study of U.S. adults.
METHODS: Cross-sectional study of serum DHEA-S and asthma in 4,212 adults (2,334 females and 1,878 males) aged 18-79 years who participated in the 2021-2023 U.S. National Health and Nutrition Examination Survey. Eosinophilic and non-eosinophilic asthma were defined by absolute blood eosinophil counts ≥ 300 and < 300 cells/uL, respectively. An asthma exacerbation was defined as an asthma attack or an emergency room or urgent care visit due to asthma in the previous year. Logistic regression was used for the multivariable analysis of DHEA-S and asthma or asthma exacerbations, which was conducted separately in females and males.
RESULTS: Serum DHEA-S levels decreased with age in male and female participants. In an analysis adjusting for other sex hormones and other covariates, serum DHEA-S levels in the fourth quartile were associated with lower odds of asthma in females (odds ratio [OR] for quartile [Q]4 vs. Q1 = 0.55, 95% confidence interval [CI]=0.30-0.98) and in males (OR for Q4 to Q1 = 0.42 [95% CI = 0.20-0.87]). Similar associations were found for non-eosinophilic asthma but not for eosinophilic asthma. There was a non-significant trend for an association between higher DHEA-S levels and reduced odds of asthma exacerbations in females with asthma (OR for Q4 to Q1 = 0.45 (95% CI = 0.20, 1.01).
CONCLUSIONS: Higher serum DHEA-S levels are associated with lower odds of asthma in a representative sample of U.S. adults.

DOI: https://doi.org/10.1093/annalsats/aaoag075
J Org Chem. 2026 Mar 27.

Synthesis of Sulfated Glycomimetics with Micromolar Affinity for Midkine.

Rocío Pereira-Jaramillo, José L de Paz, Pedro M Nieto.

A series of sulfated oligosaccharides (one tetra- and ten disaccharides) have been synthesized to study their interactions with midkine, a heparin-binding growth factor involved in cancer and inflammation. These compounds were prepared as glycosaminoglycan (GAG) mimetics and displayed hydrophobic groups at specific positions to enhance midkine binding. For the synthesis of the tetrasaccharide, a fluoro-assisted strategy was adopted. The use of an N-phenyltrifluoroacetimidate donor, instead of the analogous trichloroacetimidate, proved to be crucial in obtaining the desired tetramer with good yield. On the other hand, the synthesized disaccharides differed in the number of sulfates present and in the substituent at position 2 of the glucosamine unit. Fluorescence polarization competition experiments provided relative binding affinities for each glycomimetic expressed as IC50 values. Our results indicated that all the mimetics interacted with midkine in the micromolar range, highlighting the affinity of the 4,6-di-O-sulfated disaccharides with aromatic rings on the 2-amide group (IC50's from 3.4 ± 0.8 to 4.3 ± 1.1 μM). Overall, this study offers valuable data for the design and synthesis of high-affinity midkine ligands with potential biological applications.

DOI: https://doi.org/10.1021/acs.joc.6c00064
Psychiatry Res. 2026 Mar 20. pii: S0165-1781(26)00172-1. [Epub ahead of print]360 117111

Steroid/thyroid hormones and inflammatory markers in adolescents with ADHD: comparisons with healthy controls and modifications by methylphenidate.

Raquel Aguado-Rivas, Ana Checa-Ros, Luisa Fernández-López, Pilar Tortosa-Pinto, Raquel González-Villén, Francisco Contreras-Chova, Ana Fernández-Ibañez, Antonio Molina-Carballo.

   BACKGROUND: Increasing evidence suggests that neuroendocrine and inflammatory mechanisms may contribute to attention-deficit/hyperactivity disorder (ADHD) pathophysiology, although findings in adolescents and the effects of methylphenidate (MPH) remain limited.
OBJECTIVE: To quantify the baseline profile of activating hormones and levels of pro- and anti-inflammatory cytokines and their changes after treatment with methylphenidate (MPH) in adolescents with ADHD, in comparison with controls.
METHODS: Eighty-one adolescents (40 with ADHD and 41 healthy controls) were evaluated. Morning serum concentrations of cortisol, thyroid-stimulating hormone (TSH), dehydroepiandrosterone sulfate (DHEAS), S100B, and seven cytokines were measured. Patients with ADHD were reassessed after approximately four months of MPH treatment. Analyses considered ADHD presentation and oppositional defiant disorder (ODD) symptoms. Multivariable regression models were used to adjust biomarker associations for demographic and clinical variables.
RESULTS: Adolescents with ADHD showed significantly lower morning cortisol concentrations than controls. Several pro- and anti-inflammatory cytokines (IL-1β, IL-4, IL-5, IL-6, IL-10, and IL-13) were increased, particularly in males, whereas TNF-α and S100B did not differ between groups. Multivariable analyses confirmed independent associations between lower cortisol and higher cytokine levels with ADHD. TSH and DHEAS showed minor variations related to ODD symptoms but no consistent differences between ADHD presentations. MPH treatment improved clinical symptoms but produced no significant overall changes in hormonal or cytokine profiles CONCLUSION: Adolescents with ADHD exhibit an altered immune-hormonal profile characterized by reduced cortisol and increased circulating cytokines. These alterations appear largely independent of demographic and clinical confounders and only minimally influenced by short-term MPH treatment, suggesting persistent neuroendocrine-immune dysregulation during adolescence.

Keywords:  ADHD; Adolescents; Cortisol; Inflammation; Methylphenidate; Oppositional defiant conduct disorder

DOI:  https://doi.org/10.1016/j.psychres.2026.117111