bims-supasi 2026-01-18 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–01–18
twelve papers selected by
Jonathan Wolf Mueller, University of Birmingham

Structural and mechanistic characterization of heparin interactions with tau fibrils.
Chondroitin sulfate E activates IL-6/STAT3 signaling to drive androgen-independent growth in castration-resistant prostate cancer.
Marine-derived polysaccharides enhance the drug delivery mechanism in the management of ocular diseases: A review.
Chondrocyte-Targeted Nanoparticles Loaded with N-Acetylcysteine Protect Articular Cartilage and Attenuate Osteoarthritis by Inhibiting Ferroptosis via Glutathione Maintenance.
Long-Term Use of Proton Pump Inhibitors Affects Blood Levels of Indoxyl Sulfate in Japanese Patients with Chronic Kidney Disease.
New insights in the chronic kidney disease-associated osteoarthritis progression: Role of uremic toxin indoxyl sulfate-induced chondrocyte senescence and ferroptosis.
The Microbiome Modulates Corneal Wound Healing via the Induction of Cholesterol Sulfotransferase Pathway.
Filamentous virions act as non-infectious interfering particles to modulate papillomavirus infection.
Serum Steroid Profiling by LC-MS/MS in Distinguishing Adrenocortical Carcinoma from Other Indeterminate Adrenal Masses.
High sulfate exacerbates heavy metal toxicity in Chinese cabbage (Brassica chinensis L.) by impairing plant ROS scavenging in heavy metals contaminated soil.
Python metabolomics uncovers a conserved postprandial metabolite and gut-brain feeding pathway.
Sulfated polysaccharides from sea cucumber mitigate acetaminophen-induced acute liver injury in mice via citraconic acid-mediated inhibition of oxidative stress.

J Biol Chem. 2026 Jan 12. pii: S0021-9258(26)00023-2. [Epub ahead of print] 111153

Structural and mechanistic characterization of heparin interactions with tau fibrils.

Fiona Mon, John E Straub.

Soluble microtubule-associated tau protein can misfold and assemble into stable, insoluble amyloid fibrils. The accumulation of tau amyloid fibrils within neurons is a primary feature in the progression of neurodegenerative diseases including Alzheimer's disease. Tau fibrils have been observed to colocalize with glycosaminoglycans such as heparan sulfate in vivo. Heparin is a highly sulfated analogue of heparan sulfate that has been commonly used in vitro to accelerate tau aggregation. Binding of heparin to tau fibrils inhibits fibril uptake by neighboring cells, whereas heparan sulfate on the cell surface modulates this uptake. Understanding the molecular interactions of heparin and heparan sulfate with tau fibrils is important in developing therapeutic targets that can slow the progression of neurodegeneration. In this multiscale computational study, we employ a combination of Brownian dynamics and molecular dynamics to simulate heparin binding to two tau fibril polymorphic structures. Our simulations lead to the de novo prediction of heparin binding to basic residue ladders organized along the tau fibril axis. The mechanism of binding is facilitated by long-range electrostatic steering of the polyanionic heparin to the tau fibril surface, followed by the refinement of favorable short-range heparin-tau interactions. The identified binding sites are located in regions of excess densities in cryo-EM maps of the tau fibrils, providing support for the computational predictions. Our findings provide a structural and mechanistic framework for a better understanding of fibril-glycan interactions and how they influence the overall mechanism of tau fibril propagation.

DOI: https://doi.org/10.1016/j.jbc.2026.111153
Cell Commun Signal. 2026 Jan 13.

Chondroitin sulfate E activates IL-6/STAT3 signaling to drive androgen-independent growth in castration-resistant prostate cancer.

Hayato Ota, Kazuo Yamamoto, Shoko Nishihara.

   BACKGROUND: Castration-resistant prostate cancer (CRPC) remains a major clinical challenge, as tumor growth persists despite androgen receptor (AR) pathway inhibition. Glycosaminoglycans, particularly chondroitin sulfate (CS), are increasingly recognized as modulators of oncogenic signaling. However, the contribution of distinct sulfation motifs to therapeutic resistance is poorly understood. Here, we identify the CS-E motif as a critical regulator of IL-6/STAT3 signaling and a driver of hormone-independent growth in CRPC.
METHODS: Transcriptomic profiling (RNA-seq), real-time PCR, and flow cytometry were employed to assess CS sulfation changes in C4-2 prostate cancer cells under androgen-deprived conditions. Because reliable tools to detect CS-E have been lacking, we engineered a novel mutant lectin (Cochlin B8) with selective affinity for CS-E. This innovation enabled precise monitoring and functional characterization of CS-E on the surface of cancer cells. Functional studies combined GALNAC4S-6ST knockdown, pharmacological inhibition with Chst15-IN-1, and signaling assays to examine effects on IL-6/STAT3 activation and cell proliferation.
RESULTS: Androgen deprivation induced upregulation of GALNAC4S-6ST and enhanced CS-E biosynthesis on the cell surface. Elevated CS-E facilitated IL-6 binding to the cell surface, potentiated STAT3 phosphorylation, and sustained androgen-independent proliferation. Genetic or pharmacological inhibition of GALNAC4S-6ST significantly reduced CS-E levels, impaired IL-6 binding, attenuated STAT3 activation, and selectively suppressed proliferation under hormone-depleted conditions (IC₅₀ = 1.39 µM under androgen-deprived conditions vs. 4.46 µM under androgen-replete conditions). These effects were specific to IL-6/STAT3, with no detectable impact on AR-independent EGFR or WNT signaling pathways.
CONCLUSIONS: This study reveals a previously unrecognized mechanism whereby CS-E sustains CRPC progression by selectively enhancing IL-6/STAT3 signaling when AR signaling is suppressed. Importantly, the development of Cochlin B8 overcomes a major technical barrier in CS-E research, providing a novel tool for its specific detection and functional analysis. Targeting CS-E biosynthesis represents a promising therapeutic strategy to counter resistance and improve prostate cancer treatment.

Keywords:  Castration-resistant prostate cancer; Chondroitin sulfate E; GALNAC4S-6ST; Glycosaminoglycan; IL-6/STAT3 signaling

DOI:  https://doi.org/10.1186/s12964-026-02657-x
Int J Biol Macromol. 2026 Jan 11. pii: S0141-8130(26)00125-X. [Epub ahead of print]340(Pt 2): 150199

Marine-derived polysaccharides enhance the drug delivery mechanism in the management of ocular diseases: A review.

Mariadoss Arokia Vijaya Anand, Chia-Jung Yang, Wen-Ling Wang, Chun-Hsu Yao, Jui-Yang Lai.

  Ocular drug delivery remains significantly challenging due to complex anatomical and physiological barriers, poor bioavailability, and inefficient drug absorption. These limitations highlight the requirement for advanced delivery systems to overcome the ocular barrier and enable efficacious therapeutic outcomes. This review explores the potential of marine-derived polysaccharides as innovative carriers for ocular applications, emphasizing their potential as drug-delivery mechanisms to enhance drug retention, permeation, and bioavailability through advanced nanoplatforms. Polysaccharides such as κ-carrageenan, agarose, alginate, chitosan, hyaluronic acid, heparan sulfate, and chondroitin sulfate possess physicochemical, biocompatible, biodegradable, and mucoadhesive properties, making them ideal materials for ocular drug delivery. Notably, marine-derived polysaccharides have been reported to significantly improve ocular delivery performance, achieving up to a 3-fold increase in corneal permeability, higher drug accumulation in the aqueous humor (>47% vs. ∼20%), and approximately 3.6-3.8-fold enhancement in precorneal retention, while also enabling intelligent systems such as pH- and light-responsive drug release. These polymers have been engineered into various delivery platforms, including nanoparticles, micelles, dendrimers, nanosuspensions, hydrogels, and implants. Such systems promote sustained (long-acting), targeted (site-specific), and intelligent (stimuli-responsive) drug release, thereby significantly enhancing precorneal retention and therapeutic efficacy. These approaches are particularly relevant for treating various corneal diseases, including glaucoma, diabetic retinopathy, ocular inflammation, and age-related macular degeneration. The article also emphasizes the potential of emerging strategies to transform ocular drug delivery by offering customizable, stimuli-responsive, and patient-friendly therapeutic options. However, further in-depth research is crucial to optimize formulations, evaluate long-term safety, and address regulatory challenges for successful clinical translation.

Keywords:  Marine-derived polysaccharides; Ocular disorders; Pharmaceutical delivery technologies

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.150199
Small Sci. 2026 Jan;6(1): e202500440

Chondrocyte-Targeted Nanoparticles Loaded with N-Acetylcysteine Protect Articular Cartilage and Attenuate Osteoarthritis by Inhibiting Ferroptosis via Glutathione Maintenance.

Shaoyi Wang, Fujian Zhang, Xiaocong Zhou, Jie Yang, Zhe Li, Songlin Li, Qunshan Lu, Houyi Sun, Peilai Liu.

  Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation. Abnormal mechanical loading exacerbates intracellular ROS accumulation and glutathione (GSH) depletion. While N-acetylcysteine (NAC) has potent antioxidant properties, its therapeutic potential in OA is limited by rapid degradation and poor intraarticular retention. In this study, chondrocyte-targeted, chondroitin sulfate (CS)-modified PLGA nanoparticles (CS-NAC-NPs) is developed for sustained and localized delivery of NAC. These nanoparticles exhibit excellent physical and chemical properties, biocompatibility, and chondrocyte targeting capabilities. In vitro, CS-NAC-NPs attenuated mechanical stress-induced ROS accumulation, preserved mitochondrial integrity, restored GSH levels, and suppressed ferroptosis, as evidenced by increased GPX4 expression and improved chondrocyte viability. In a murine model of OA, intraarticular injection of CS-NAC-NPs significantly reduced cartilage degradation and osteophyte formation, improved histological scores, and maintained extracellular matrix homeostasis more effectively than free NAC or nontargeted NAC-NPs. Notably, the therapeutic effect is abolished in GPX4-deficient mice, confirming that CS-NAC-NPs act via GPX4-mediated ferroptosis inhibition. Furthermore, in vivo tracking demonstrated excellent joint retention and no off-target toxicity, underscoring their translational safety. This study introduces a novel nanotherapeutic platform that couples biomechanical targeting with redox-responsive delivery to modulate ferroptosis, offering a promising disease-modifying approach for OA treatment.

Keywords:  N‐acetylcysteine; ferroptosis; glutathione; nanoparticle; osteoarthritis

DOI:  https://doi.org/10.1002/smsc.202500440
Biol Pharm Bull. 2026 ;49(1): 84-89

Long-Term Use of Proton Pump Inhibitors Affects Blood Levels of Indoxyl Sulfate in Japanese Patients with Chronic Kidney Disease.

Kotaro Kawamoto, Shota Kadomura, Maki Nabeki, Hiroaki Sasaki, Kanji Yamada, Manabu Noda, Hajime Masuda, Shirou Tsuchida, Tatsuya Itoh, Michiya Kobayashi.

  Proton pump inhibitors (PPIs) are implicated in the progression of chronic kidney disease (CKD), but the mechanism behind this is unclear. PPIs are known to inhibit organic anion transporters (OATs) and affect intestinal microbiota. PPI use may influence serum concentrations of indoxyl sulfate (IS), a uremic toxin that contributes to CKD. This study compares serum IS concentrations between Japanese patients receiving long-term PPI prescriptions and those receiving non-PPIs, evaluating the effect of long-term PPI therapies on serum IS concentrations. This single-center, cross-sectional study included patients with an estimated glomerular filtration rate (eGFR) of 15 to 44 mL/min/1.73 m,2 who attended an outpatient visit at a nephrology and/or diabetes department between October 2022 and December 2023. Serum IS concentrations were measured by HPLC. The analysis included 29 patients in the PPI group and 28 in the non-PPI group; serum IS concentrations were significantly higher in the PPI group [median (interquartile range) 15.37 (9.69-19.80) µM] and non-PPI group [median (interquartile range) 10.66 (6.97-14.19) µM], p = 0.03. Multiple regression analysis was performed, linking prescription of PPIs and lower eGFR to higher serum IS levels. This study highlights an apparent association of long-term prescriptions of PPIs with high serum IS concentrations. However, more detailed studies are required to evaluate the contribution of intestinal microbiota and diet to this phenomenon.

Keywords:  chronic kidney disease; indoxyl sulfate; proton pump inhibitor; uremic toxin

DOI:  https://doi.org/10.1248/bpb.b25-00465
Life Sci. 2026 Jan 12. pii: S0024-3205(26)00019-6. [Epub ahead of print]388 124211

New insights in the chronic kidney disease-associated osteoarthritis progression: Role of uremic toxin indoxyl sulfate-induced chondrocyte senescence and ferroptosis.

Yao-Pang Chung, Ya-Wen Chen, Chun-Fa Huang, Te-I Weng, Rong-Sen Yang, Shing-Hwa Liu.

   AIMS: Epidemiological data have shown a notably high co-occurrence of osteoarthritis (OA) and chronic kidney disease (CKD). The pathological mechanisms for CKD-associated OA still remain to be clarified. Uremic toxin Indoxyl Sulfate (IS), accumulated in CKD, may play a role in OA pathology. This study aimed to clarify the role of IS in CKD-associated OA and investigated the involvement of chondrocyte senescence and ferroptosis through the crosstalk between calcium and iron metabolism.
MATERIALS AND METHODS: Human chondrocytes were treated with IS and co-treated with either calcium chelator BAPTA or iron chelator Deferoxamine (DFO). Cellular senescence and ferroptosis were assessed. An adenine-induced CKD mouse model was utilized to evaluate OA features and molecular mechanisms with or without oral adsorbent AST-120 (reducing IS levels) or DFO treatment.
KEY FINDINGS: IS exposure elevated intracellular iron and calcium, triggering chondrocyte lipid peroxidation, senescence and ferroptosis via the calpain-1/interleukin-1α signaling axis, which could be reversed by both BAPTA and DFO treatment. IS-increased intracellular iron levels could be reversed by DFO, but not BAPTA. In vivo, reducing IS levels with AST-120 or iron chelation with DFO alleviated cartilage degradation and iron accumulation. Protein expression patterns in the joint tissues mirrored those observed in cell culture.
SIGNIFICANCE: Our findings demonstrate for the first time that IS promotes both calcium influx and iron accumulation, leading to enhanced chondrocyte lipid peroxidation, senescence and ferroptosis. These effects may underlie the mechanistic link between CKD and OA comorbidity. IS may thus represent a critical bridge between kidney dysfunction and joint degeneration.

Keywords:  Chronic kidney disease-associated osteoarthritis (CKD-OA); Ferroptosis; Senescence; Uremic toxin

DOI:  https://doi.org/10.1016/j.lfs.2026.124211
FASEB J. 2026 Jan 31. 40(2): e71429

The Microbiome Modulates Corneal Wound Healing via the Induction of Cholesterol Sulfotransferase Pathway.

Mamoru Ogawa, Yosuke Isobe, Haruki Uchino, Masatoshi Hirayama, Tamotsu Kato, Kazuno Negishi, Makoto Arita.

  The ocular surface is in direct contact with the external environment and is susceptible to injury from dust, dryness, or other foreign objects. Once corneal injury occurs, a local inflammatory response is triggered, followed by effective repair of the epithelial layer. In this study, we demonstrated that antibiotic treatment delayed corneal wound healing in mice. LC-MS/MS-based untargeted lipidomics and qPCR analyses revealed that the levels of cholesterol sulfate (CS) and the CS-synthesizing enzyme SULT2B1 were significantly upregulated by antibiotic treatment, and SULT2B1 knockout mice exhibited accelerated corneal wound healing along with increased recruitment of neutrophils and eosinophils. Topical application of CS delayed corneal wound healing. In vitro scratch assays revealed that CS delayed the wound healing of human corneal epithelial cells, potentially by inhibiting the DOCK2-Rac pathway. These results highlight the role of commensal bacteria in controlling corneal wound healing via the cholesterol-sulfotransferase pathway.

Keywords:  cholesterol sulfate; commensal bacteria; corneal wound healing; lipid mediators; lipidomics; metabolomics; microbiota; ocular surface; sulfotransferase (SULT); sulfuryltransferase

DOI:  https://doi.org/10.1096/fj.202503669R
J Virol. 2026 Jan 13. e0203925

Filamentous virions act as non-infectious interfering particles to modulate papillomavirus infection.

Dominik van Bodegraven, Sreedeepa Saha, Lilo Greune, Reinhard Kirnbauer, Petra Dersch, Mario Schelhaas.

  Genus beta (β) human papillomaviruses (HPVs) potentially contribute to the development of non-melanoma skin cancer. Yet, comparatively little is known about their biology. In particular, details about initial infection, i.e., host cell entry, remain mostly elusive. During initial characterization of β HPV5 pseudovirion (PsV) preparations, surprisingly large amounts of filamentous particles were found besides the prototypical icosahedral (T = 7) virions. Whether these filamentous particles actively contribute to or interfere with infectivity of the spherical viruses is unknown. Using a combination of morphological, biochemical, and virological methods, we showed that the filamentous particles are non-infectious. Moreover, they interfered with the initial step of infection, i.e., binding to cellular heparan sulfate proteoglycans (HSPGs), and served as a decoy for soluble glycosaminoglycans, thereby modulating infectivity by enhancing infectious PsV binding. This explains previous seemingly contradictory findings on HPV5 binding to HSPGs. Importantly, in HPV5 skin warts from an immunocompromised patient, no filamentous particles were observable highlighting differences in the assembly of pseudovirions and native viruses.IMPORTANCEPapillomaviruses contribute to numerous cancer incidents and significant mortality despite available vaccinations. Hence, high-risk α HPVs have been the focus of most research in the past. However, there are indications that less well-studied β HPVs may also contribute to certain malignancies. Little is known about their mode of cell invasion, and available data appear partially contradictory. Our work demonstrated that HPV5 as a model β HPVs yielded high amounts of non-infectious filamentous particles during PsV production. These acted as modulators of infection by the infectious spherical particles. Removing these filamentous particles showed that HPV5 engaged HSPGs as the primary receptor for cell binding, similar to high-risk α HPV, indicating a conserved feature not only among α, but also among β HPVs, thereby explaining previous contradictions.

Keywords:  defective interfering particles; human papillomavirus; virus entry; virus structure; virus-host interaction

DOI:  https://doi.org/10.1128/jvi.02039-25
J Steroid Biochem Mol Biol. 2026 Jan 14. pii: S0960-0760(26)00003-8. [Epub ahead of print] 106937

Serum Steroid Profiling by LC-MS/MS in Distinguishing Adrenocortical Carcinoma from Other Indeterminate Adrenal Masses.

Archana Rao, Aditya Phadte, Anuj Ban, Saba Samad Memon, Manjiri Karlekar, Anurag Ranjan Lila, Vijaya Sarathi, Nimmi Kansal, Rohit Barnabas, Padma Vikram Badhe, Gwendolyn Fernandes, Sameer Rege, Gagan Prakash, Santosh Menon, Nalini Shah, Tushar Bandgar.

  For an adrenal incidentaloma with indeterminate imaging characteristics, urine multisteroid profiling is suggested for diagnosing adrenocortical carcinoma (ACC). Data on the utility of serum steroid metabolomics in this context is limited to a few studies. Here, we present data of 62 adult patients with indeterminate unilateral adrenal masses (size ≥3cm and basal attenuation ≥10HU) where baseline serum liquid chromatography-tandem mass spectrometry (LC-MS/MS) multisteroid profiling was available. Logistic regression was used to identify the key steroid signature for differentiating ACC from other non-ACC adrenal masses. Among 62 patients (median age: 41 years, 31 males), 37 (59.6%) had ACC. The non-ACC cohort (n=25) comprised pheochromocytoma (n=9), adrenocortical adenoma (n=8), metastases (n=4), schwannoma (n=2), ganglioneuroma (n=1), and lymphoma (n=1). Tumour size was significantly larger in the ACC cohort (9.9 vs 7.0cm; p < 0.001) than the non-ACC cohort. Nine of 13 steroids were significantly elevated in ACC: 11-deoxycorticosterone (DOC), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol (S), cortisone (E), androstenedione (A4), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulphate (DHEAS) in both sexes, as well as testosterone (T) in females and progesterone (P4) in males. After excluding sex-dependent steroids, univariate analysis yielded six significant steroids (17OHP, S, E, A4, DHEA, and DHEAS). A multivariate logistic regression model with backward elimination identified A4, S, and DHEAS as the best discriminators (AUC:0.923), with a cutoff of 0.52 yielding 83.8% sensitivity and 96% specificity for diagnosing ACC. Our study results suggest serum LC-MS/MS profiling of three steroids (A4, S, and DHEAS) provides a non-invasive approach to distinguish ACC from other indeterminate adrenal masses.

Keywords:  Adrenocortical Carcinoma; LC-MS/MS; Steroid profiling

DOI:  https://doi.org/10.1016/j.jsbmb.2026.106937
BMC Plant Biol. 2026 Jan 13.

High sulfate exacerbates heavy metal toxicity in Chinese cabbage (Brassica chinensis L.) by impairing plant ROS scavenging in heavy metals contaminated soil.

Longfei Xu, Xi Song, Shirong Zhang, Daixi Zhang, Ting Li, Guiyin Wang, Xiaoxun Xu, Xiaomei Pan, Wei Zhou, Yulin Pu, Yongxia Jia.

  Accumulation of heavy metals (HMs) and sulfates in farmland near mines is one of the most serious environmental problems posing a threat to crops and human health. Moderate sulfate alleviates the toxicity of HMs in crops, but the impact of high sulfate on crops in HM-contaminated soil remains unclear. Hence, we integrated physiological, transcriptomic and metabolomic profiling to investigate the effect of high sulfate on Chinese cabbage (Brassica chinensis L.) under HMs through controlled pot experiments. According to our results, compared with the HMs only group, the growth indicators of Chinese cabbage in the HMs plus high sulfate group decreased by 11.94% to 49.19%, and photosynthesis was significantly inhibited (p < 0.05). Notably, potential biomarkers indicating high sulfate were identified: catalase, fructose-bisphosphate aldolase 2, senescence-associated gene 21, ferritin-1, and 2-Aminoadipic acid. Mechanistically, high sulfate intensified oxidative damage by suppressing the synthesis of glutathione (with a 43.43% reduction) and γ-aminobutyric acid (with a 15.19% decline), consequently resulting in a 21.79% increase in reactive oxygen species (ROS) within the leaves. The excessive accumulation of ROS appeared to directly initiate programmed cell death, induced cellular damage in roots and leaves, and might enhance autophagic degradation of chloroplasts and the endoplasmic reticulum. Then, photosynthesis, sucrose synthesis, amino acid anabolism, and energy production pathways were disrupted, leading to the further reduction of Chinese cabbage biomass. Consequently, this study emphasized the harmful effects of high sulfate on Chinese cabbage in HM-contaminated soil through disrupting the ROS clearance function of Chinese cabbage.

Keywords:  Farmland contaminants; Heavy metals; Multi-omics; Plant stress; Toxicological mechanism

DOI:  https://doi.org/10.1186/s12870-026-08103-x
bioRxiv. 2026 Jan 10. pii: 2026.01.09.698526. [Epub ahead of print]

Python metabolomics uncovers a conserved postprandial metabolite and gut-brain feeding pathway.

Shuke Xiao, Mengjie Wang, Thomas G Martin, Barry Scott, Xing Fang, Xinming Liu, Yongjie Yang, Sipei Fu, Steven D Truong, Jack F Gugel, Gregory L Maas, Marcus P Mullen, Jennifer Hampton Hill, Veronica L Li, Andrew L Markhard, Mingming Zhao, Wei Qi, Saranya C Reghupaty, Meng Zhao, Jan Spaas, Wei Wei, Trine Moholdt, John A Hawley, Christian T Voldstedlund, Erik A Richter, Xiaoke Chen, Katrin J Svensson, Daniel Bernstein, Leslie A Leinwand, Yong Xu, Jonathan Z Long.

Most mammals consume small and frequent meals. By contrast, pythons are ambush predators that exhibit extreme feeding and fasting patterns and provide a unique model for uncovering molecular mediators of the postprandial response 1-3 . Using untargeted metabolomics, here we show that circulating levels of the metabolite para -tyramine-O-sulfate (pTOS) are increased >1,000-fold in pythons after a single meal. In pythons, pTOS production occurs in a microbiome-dependent manner via sequential decarboxylation and sulfation of dietary tyrosine. In both pythons and mice, pTOS administration activates a neural population in the ventromedial hypothalamus (VMH). In mice, these VMH neurons are required for the anorexigenic effects of pTOS. Chronic administration of pTOS to diet-induced obese male mice suppresses food intake and body weight. pTOS is also present in human blood, where its levels are increased after a meal. Together, these data uncover a conserved postprandial anorexigenic metabolite that links nutrient intake to energy balance.

DOI: https://doi.org/10.64898/2026.01.09.698526
Food Funct. 2026 Jan 13.

Sulfated polysaccharides from sea cucumber mitigate acetaminophen-induced acute liver injury in mice via citraconic acid-mediated inhibition of oxidative stress.

Jiacheng Cheng, Weiyun Zheng, Jiayi Yan, Shuang Song, Chunqing Ai.

Acetaminophen (APAP) is a widely used antipyretic and analgesic drug, but excessive or prolonged use can cause liver injury. Sulfated polysaccharides from sea cucumber (SCSP) exhibit diverse bioactivities; however, their protective role against APAP hepatotoxicity remains unclear. Here, SCSP pretreatment significantly alleviated APAP-induced liver injury in mice, as evidenced by reduced hepatic necrosis, serum transaminases, inflammation, and oxidative stress. 16S rRNA sequencing revealed that SCSP preserved gut microbial diversity and enriched beneficial bacterial taxa, partially counteracting APAP-induced dysbiosis. Metabolomics analysis further demonstrated that SCSP remodeled microbiota metabolic outputs and mitigated APAP-induced serum metabolic abnormalities, particularly in amino acid metabolism. Notably, citraconic acid (CA) was identified as a key metabolite restored by SCSP and strongly associated with improved hepatic outcomes, with concordant changes observed between gut and serum. Functional validation confirmed that CA pretreatment protected against APAP-induced liver injury by enhancing antioxidative defenses and reducing inflammatory responses. In vitro, CA reduced oxidative damage and activated the Nrf2 pathway. Collectively, these results support SCSP as a promising preventive prebiotic that enhances hepatic resilience to APAP challenge via modulation of the gut-liver axis, with CA representing an important mechanistic mediator.

DOI: https://doi.org/10.1039/d5fo04767f