bims-supasi 2024-11-17 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2024–11–17
seventeen papers selected by
Jonathan Wolf Mueller, University of Birmingham

High-throughput glycosaminoglycan extraction and UHPLC-MS/MS quantification in human biofluids.
Antiviral efficacy of heparan sulfate and enoxaparin sodium against SARS-CoV-2.
Chondroitin Sulfate-Coated Heteroduplex-Molecular Spherical Nucleic Acids.
Chondroitin sulfate sponge scaffold for slow-release Mg2+/Cu2+ in diabetic wound management: Hemostasis, effusion absorption, and healing.
Systematic Characteristics of Fucoidan: Intriguing Features for New Pharmacological Interventions.
Harnessing Free Sulfate Groups in Glycosylation Reactions.
Synthesis and evaluation of photoaffinity labeling reagents for identifying binding sites of sulfated neurosteroids on NMDA and GABAA receptors.
Degree of sulfation of freeze-dried calcium alginate sulfate scaffolds dramatically influence healing rate of full-thickness diabetic wounds.
Fucosylated chondroitin sulfate alleviates diet-induced obesity by modulating intestinal lipid metabolism and colonic microflora.
Macrophages producing chondroitin sulfate proteoglycan-4 induce neuro-cardiac junction impairment in Duchenne muscular dystrophy.
Effects of Novel Cross-Linked Chondroitin Sulfate (SI-449) as a Postoperative Anti-Adhesion Barrier.
Inhibition of Cancer Cell Migration and Invasion In Vitro by Recombinant Tyrosine-Sulfated Haemathrin, A Thrombin Inhibitor.
Reducing the levels of indoxyl sulfate in patients undergoing dialysis: a promising approach to managing inflammation and the redox state of human serum albumin.
Sulfated galactofucan from Sargassum fusiforme protects against postmenopausal osteoporosis by regulating bone remodeling.
Structural, Functional, and Bioactive Properties of Sulfated Polysaccharides from Skipjack Tuna Skin as a Function of Drying Techniques.
Slc26a2-mediated sulfate metabolism is significant for the tooth development.
Heparan sulphate binding controls in vivo half-life of the HpARI protein family.

Nat Protoc. 2024 Nov 14.

High-throughput glycosaminoglycan extraction and UHPLC-MS/MS quantification in human biofluids.

Nicola Volpi, Fabio Galeotti, Francesco Gatto.

Glycosaminoglycans (GAGs) are linear, unbranched heteropolysaccharides whose structural complexity determines their function. Accurate quantification of GAGs in biofluids at high throughput is relevant for numerous biomedical applications. However, because of the structural variability of GAGs in biofluids, existing protocols require complex pre-analytical procedures, have limited throughput and lack accuracy. Here, we describe the extraction and quantification of GAGs by using ultra-high-performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-MS/MS). Designed for 96-well plates, this method enables the processing of up to 82 study samples per plate, with the remaining 14 wells used for calibrators and controls. Key steps include the enzymatic depolymerization of GAGs, their derivatization with 2-aminoacridone and their quantification via UHPLC-MS/MS. Each plate can be analyzed in a single UHPLC-MS/MS run, offering the quantitative and scalable analysis of 17 disaccharides from chondroitin sulfate, heparan sulfate and hyaluronic acid, with a level of precision and reproducibility sufficient for their use as biomarkers. The procedure from sample thawing to initiating the UHPLC-MS/MS run can be completed in ~1.5 d plus 15 min of MS runtime per sample, and it is structured to fit within ordinary working shifts, thus making it a valuable tool for clinical laboratories seeking high-throughput analysis of GAGs. The protocol requires expertise in UHPLC-MS/MS.

DOI: https://doi.org/10.1038/s41596-024-01078-9
Arch Pharm (Weinheim). 2024 Nov 09. e2400545

Antiviral efficacy of heparan sulfate and enoxaparin sodium against SARS-CoV-2.

Virginia Fuochi, Salvatore Furnari, Giuseppe Floresta, Vincenzo Patamia, Chiara Zagni, Filippo Drago, Antonio Rescifina, Pio Maria Furneri.

  As the world transitions from the acute phase of the COVID-19 pandemic caused by SARS-CoV-2, the scientific community continues to explore various therapeutic avenues to control its spread and mitigate its ongoing effects. Among the promising candidates are heparan sulfate (HS) and enoxaparin (EX), which have emerged as potential virus inhibitors. HS, a type of glycosaminoglycan, plays a prominent role in the attachment of the virus to host cells. At the same time, EX, a low-molecular-weight heparin, is being investigated for its ability to disrupt the interaction between the spike protein of SARS-CoV-2 and the ACE2 receptor in human cells. Understanding the mechanisms through which these substances operate could lay the foundation for new strategies in the ongoing management of COVID-19. This study aimed to examine the details of SARS-CoV-2's entry mechanisms and the role of HS in this process. Furthermore, it examines EX's mechanism of action, highlighting how it potentially inhibits SARS-CoV-2. The interactions between HS and the virus, alongside in-vitro and in-silico inhibition studies with HS and EX, are critically analyzed to assess their antiviral efficacy. Additionally, the antiviral activity of sulfated polysaccharides and the potential therapeutic applications of these findings are discussed.

Keywords:  ACE2; SARS‐CoV‐2; absorption inhibition; glycosaminoglycans; molecular docking

DOI:  https://doi.org/10.1002/ardp.202400545
Chembiochem. 2024 Nov 15. e202400908

Chondroitin Sulfate-Coated Heteroduplex-Molecular Spherical Nucleic Acids.

Pasi Virta, Toni Laine, Prasannakumar Deshpande, Ville Tähtinen, Eleanor T Coffey.

  Molecular Spherical Nucleic Acids (MSNAs) are atomically uniform dendritic nanostructures and potential delivery vehicles for oligonucleotides. The radial formulation combined with covalent conjugation may hide the oligonucleotide content and simultaneously enhance the role of appropriate conjugate groups on the outer sphere. The conjugate halo may be modulated to affect the delivery properties of the MSNAs. In the present study, [60]fullerene-based molecular spherical nucleic acids, consisting of a 2'-deoxyribonucleotide and a ribonucleotide sequence, were used as hybridization-mediated carriers (''DNA and RNA-carriers'') for an antisense oligonucleotide, suppressing Tau protein, (i.e. Tau-ASO) and its conjugates with chondroitin sulfate tetrasaccharides (CS) with different sulfation patterns. The impact of the MSNA carriers, CS-moieties on the conjugates and the CS-decorations on the MSNAs on cellular uptake and - activity (Tau-suppression) of the Tau-ASO was studied with hippocampal neurons in vitro. The formation and stability of these heteroduplex ASO-MSNAs were evaluated by UV melting profile analysis, polyacrylamide gel electrophoresis (PAGE), dynamic light scattering (DLS) and size exclusion chromatography equipped with a multi angle light scattering detector (SEC-MALS). The cellular uptake and - activity were studied by confocal microscopy and Western blot analysis, respectively.

Keywords:  Molecular Spherical Nucleic Acids, Chondroitin sulfate, [60]fullerene conjugates, Drug delivery, heteroduplex antisense oligonucleotides

DOI:  https://doi.org/10.1002/cbic.202400908
Int J Biol Macromol. 2024 Nov 11. pii: S0141-8130(24)08371-5. [Epub ahead of print] 137561

Chondroitin sulfate sponge scaffold for slow-release Mg2+/Cu2+ in diabetic wound management: Hemostasis, effusion absorption, and healing.

Fengyi Zhu, Qiulan Wen, Yuting Hu, Jun Gong, Xibing Zhang, Chaoyang Huang, Hai Zhou, Lianglong Chen, Li Yu.

  The management of diabetic wounds presents significant challenges due to persistent inflammation, microenvironmental disruptions, and impaired angiogenesis. To address these issues, this study developed a multifunctional chondroitin sulfate sponge (CSP@Cu-Mg) with anti-inflammatory properties, hemostatic effects, effusion absorption, and enhanced healing promotion. Through ion crosslinking, MgO and CuO were incorporated into the interpenetrating network structure of chondroitin sulfate and acellular dermal matrix, resulting in a sponge with impressive liquid absorption capacity (3450 %) and porosity (83 %). This sponge enabled sustained release of Mg2+/Cu2+ ions, with approximately 40 % cumulative release over 7 days. This release helped reduce inflammation, promote the proliferation and migration of skin repair-related cells, and stimulate angiogenesis. In vivo studies demonstrated that the CSP@Cu-Mg sponge significantly improved diabetic wound healing by modulating inflammation and accelerating collagen deposition, angiogenesis, and re-epithelialization. This extracellular matrix sponge, which synergistically releases Mg2+/Cu2+, presents a promising strategy for comprehensive diabetic wound management with substantial clinical implications.

Keywords:  Acellular dermal matrix; Chondroitin sulfate; Copper oxide; Diabetic wound; Magnesium oxide

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.137561
Int J Mol Sci. 2024 Nov 01. pii: 11771. [Epub ahead of print]25(21):

Systematic Characteristics of Fucoidan: Intriguing Features for New Pharmacological Interventions.

Seungjin Jeong, Seokmin Lee, Geumbin Lee, Jimin Hyun, Bomi Ryu.

  Fucoidan, a sulfated polysaccharide found primarily in brown algae, is known for exhibiting various biological activities, many of which have been attributed to its sulfate content. However, recent advancements in techniques for analyzing polysaccharide structures have highlighted that not only the sulfate groups but also the composition, molecular weight, and structures of the polysaccharides and their monomers play a crucial role in modulating biological effects. This review comprehensively provides the monosaccharide composition, degree of sulfation, molecular weight distribution, and linkage of glycosidic bonds of fucoidan, focusing on the diversity of its biological activities based on various characteristics. The implications of these findings for future applications and potential therapeutic uses of fucoidan are also discussed.

Keywords:  biological activity; brown algae; fucoidan; molecular weight; monosaccharide; structure; sulfation

DOI:  https://doi.org/10.3390/ijms252111771
Angew Chem Int Ed Engl. 2024 Nov 14. e202416743

Harnessing Free Sulfate Groups in Glycosylation Reactions.

Yuta Maki, Akihiro Manbo, Abe Junpei, Hiroki Nobutou, Kohtaro Hirao, Ryo Okamoto, Masayuki Izumi, Shusuke Yamanaka, Mitsutaka Okumura, Yasuhiro Kajihara.

  General strategies for synthesizing sulfated oligosaccharides employ the protection of sulfate groups for glycosylation or post-sulfation after the synthesis of oligosaccharides. However, the chemical behavior of free sulfate groups in glycosylation reactions has not been thoroughly studied. We examined several glycosyl donors with free sulfate groups, but neither glycosyl imidates nor thioglycosides achieved products. Conversely, activating 6-sulfated GalNAc donors with either a 2-NTroc group or 2-O-acetyl group using an ortho-hexynylbenzoate group at the anomeric position yielded β-glycosides in good yield. These results indicate that glycosylations with a free sulfate group can be performed and that the neighboring group participation of 2-NHTroc and 2-O-acetyl groups works even with an unprotected sulfate group at 6-position. Ab initio calculations supported the formation of acyloxionium-cation via 2-O-acyl participation. Additionally, glycosylation reactions under various counter cations of the sulfate group, such as Na+, Li+, K+, Ba2+ and pyridinium were examined. Results showed that sodium and lithium salt donors yielded the products in good yield. These results were also supported by ab initio calculations. Practical glycosylation reactions between disaccharide donor-acceptor pairs with free sulfate groups successfully yielded the sulfated tetrasaccharides. This study also discusses how a sodium salt acts as a protecting group during glycosylation.

Keywords:  chondroitin sulfate; free sulfate group; glycosaminoglycan; glycosylation

DOI:  https://doi.org/10.1002/anie.202416743
RSC Adv. 2024 Nov 11. 14(49): 36352-36369

Synthesis and evaluation of photoaffinity labeling reagents for identifying binding sites of sulfated neurosteroids on NMDA and GABAA receptors.

Mingxing Qian, Yuanjian Xu, Hong-Jin Shu, Zi-Wei Chen, Lei Wang, Charles F Zorumski, Alex S Evers, Steven Mennerick, Douglas F Covey.

The endogenous neurosteroids dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate (PS) are allosteric modulators of γ-aminobutyric acid type A (GABAA) and N-methyl-d-aspartate (NMDA) type glutamate receptors. Analogues of these endogenous steroid sulfates can be either positive or negative allosteric modulators (PAMs or NAMs, respectively) of these receptors, but there is limited information about the steroid-protein binding interactions that mediate these effects and photoaffinity labeling reagents (PALs) of sulfated steroids have not been reported previously. The synthesis of a panel of ten sulfated steroid analogues containing a diazirine group, five of which also contain an alkyne group for click chemistry reactions, for use in photoaffinity labeling studies to identify binding sites for steroid sulfates that are either positive or negative allosteric modulators is reported. Electrophysiological measurements on cultured rat hippocampal neurons were made to determine the modes of allosteric modulation in comparison to those of PS on both receptors. PALs with the activity profile of PS (NMDA PAM, GABAA NAM) were identified. Unexpectedly, PALs with PAM activity at both receptors were also found. Photolabeling of both receptors by two of the PALs was performed to demonstrate their utility, and by inference those of the other PALs, for future studies to identify binding sites for endogenous steroid sulfates on both receptors.

DOI: https://doi.org/10.1039/d4ra07074g
Int J Biol Macromol. 2024 Nov 12. pii: S0141-8130(24)08367-3. [Epub ahead of print] 137557

Degree of sulfation of freeze-dried calcium alginate sulfate scaffolds dramatically influence healing rate of full-thickness diabetic wounds.

Maryam Zare-Gachi, Amin Sadeghi, Mahmoud Alipour Choshali, Tayyeb Ghadimi, Siamak Farokh Forghani, Mohamad Pezeshki-Modaress, Hamed Daemi.

  Diabetic foot ulcer (DFU) is a chronic and non-healing wound in all age categories with a high prevalence and mortality in the world. An ideal wound dressing for DFU should possess the ability of adsorbing high contents of exudate and actively promote wound healing. Here, we introduced the calcium alginate sulfate as a new biomaterial appropriate for use in wound dressing to promote the healing of full-thickness ulcers in a diabetic mouse model. In this regard, alginate sulfate (Alg-S) solutions with different degree of substitution (DS) of 0.2, 0.5, and 0.9 were synthesized, freeze-dried, crosslinked by calcium cations, purified by washing and refreeze-dried. Primary analyses including swelling ratio, porosity content and mechanical properties revealed that all Alg-S scaffolds possess necessities for use as a wound dressing. After confirming the cytocompatibility of both alginate and alginate sulfate-based scaffolds by MTT assay, they were used as wound dressing for healing of full-thickness ulcers in diabetic mice. The results of wound healing process confirmed that calcium alginate sulfate scaffolds can heal the wounds faster than both alginate-treated and non-treated wounds. Furthermore, the histological analyses of healed tissues reveled normal regeneration of the skin tissue layers and collagen deposition similar to the healthy tissue.

Keywords:  Alginate sulfate; Diabetic foot ulcer; Scaffold; Wound dressing; Wound healing

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.137557
Int J Biol Macromol. 2024 Nov 07. pii: S0141-8130(24)08180-7. [Epub ahead of print] 137371

Fucosylated chondroitin sulfate alleviates diet-induced obesity by modulating intestinal lipid metabolism and colonic microflora.

Shan Li, Ronghua Guo, Xiang Gao, Yin Wang, Jiaxin Wen, Ting Zhao, Xiaofei Guo, Junhui Li, Shiguo Chen, Duo Li.

  Fucosylated chondroitin sulfate from Pearsonothuria graeffei (FCS-Pg), a natural macromolecular polysaccharide, has been proven to prevent obesity, but its underlying molecular mechanism is still unclear. C57BL/6 J mice fed on high fat diet (HFD) were administered FCS-Pg lasting for ten weeks. The results demonstrated that FCS-Pg supplementation reduced body weight with dosage manner compared with HFD group. The expressions of intestinal lipid synthesis related proteins such as cluster of differentiation 36 (CD36) in FCS-Pg group were lower than those in the HFD group. Compared with the normal group, HFD caused gut microbiota disorder in the colon. FCS-Pg supplementation at high dosage restored the gut microbiota composition with higher abundance of Alistipes and Bacteroidetes and lower abundance of Colidextribacter, Bilophila and Firmicutes compared with HFD group. Moreover, FCS-Pg decreased the expression of proteins involved in triglyceride synthesis such as glycerol 3-phosphate dehydrogenase 1 (GPD1) and increased the expression of proteins involved in lipolysis and thermogenesis such as adipose triglyceride lipase (ATGL) and uncoupling protein 1 (UCP1) in the white adipose tissue (WAT) compared with HFD group. In conclusion, our study suggested that FCS-Pg significantly prevented obesity and improved WAT function in HFD-fed mice by regulating intestinal lipid metabolism and microflora composition.

Keywords:  Fucosylated chondroitin sulfate; Gut microbiota; Lipid metabolism

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.137371
J Pathol. 2024 Nov 11.

Macrophages producing chondroitin sulfate proteoglycan-4 induce neuro-cardiac junction impairment in Duchenne muscular dystrophy.

Marika Milan, Fabio Maiullari, Maila Chirivì, Maria Grazia Ceraolo, Rebecca Zigiotto, Andrea Soluri, Silvia Maiullari, Elisa Landoni, Dario Di Silvestre, Francesca Brambilla, Pierluigi Mauri, Veronica De Paolis, Nicole Fratini, Maria Cristina Crosti, Chiara Cordiglieri, Chiara Parisi, Antonella Calogero, Dror Seliktar, Yvan Torrente, Chiara Lanzuolo, Gianpietro Dotti, Mirco Toccafondi, Mauro Bombaci, Elena De Falco, Claudia Bearzi, Roberto Rizzi.

  Duchenne muscular dystrophy (DMD) is caused by the absence of the full form of the dystrophin protein, which is essential for maintaining the structural integrity of muscle cells, including those in the heart and respiratory system. Despite progress in understanding the molecular mechanisms associated with DMD, myocardial insufficiency persists as the primary cause of mortality, and existing therapeutic strategies remain limited. This study investigates the hypothesis that a dysregulation of the biological communication between infiltrating macrophages (MPs) and neurocardiac junctions exists in dystrophic cardiac tissue. In a mouse model of DMD (mdx), this phenomenon is influenced by the over-release of chondroitin sulfate proteoglycan-4 (CSPG4), a key inhibitor of nerve sprouting and a modulator of the neural function, by MPs infiltrating the cardiac tissue and associated with dilated cardiomyopathy, a hallmark of DMD. Givinostat, the histone deacetylase inhibitor under current development as a clinical treatment for DMD, is effective at both restoring a physiological microenvironment at the neuro-cardiac junction and cardiac function in mdx mice in addition to a reduction in cardiac fibrosis, MP-mediated inflammation, and tissue CSPG4 content. This study provides novel insight into the pathophysiology of DMD in the heart, identifying potential new biological targets. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Keywords:  DMD heart failure; cardiac fibrosis; cardiac innervation; dilated cardiomyopathy; extracellular matrix; inflammation; macrophages; proteoglycans

DOI:  https://doi.org/10.1002/path.6362
J Surg Res. 2024 Nov 14. pii: S0022-4804(24)00668-1. [Epub ahead of print]304 162-172

Effects of Novel Cross-Linked Chondroitin Sulfate (SI-449) as a Postoperative Anti-Adhesion Barrier.

Kei Toyama, Katsuya Takahashi, Sho Funayama, Keiji Yoshioka.

   INTRODUCTION: Postoperative adhesion often develops as a natural physiological response following abdominal and pelvic surgeries. Although existing resorbable adhesion barriers have reduced the incidence of postoperative adhesion formation, their clinical efficacy requires improvement. In this study, we generated a novel cross-linked, powder-formed chondroitin sulfate (SI-449) as an effective postoperative anti-adhesion barrier. We evaluated its anti-adhesion effect in animal models of abdominal and pelvic surgeries and elucidated its mechanism of action.
METHODS: Rats in the cecum-abraded adhesion and uterine horn adhesion models were treated with SI-449 and Seprafilm, and adhesion frequency and scores were evaluated. The mechanisms underlying this anti-adhesion effect were examined histopathologically using a cecum-abraded adhesion model.
RESULTS: In the cecum-abraded adhesion model, SI-449 reduced the adhesion frequency and total adhesion score to 30% and 1.6, respectively, compared with 100% and 8.1 in the control group and 50% and 2.5 in the Seprafilm group. We observed an SI-449-like substance between the cecum and abdominal wall and no fibrin net structure connecting the invasive tissues after surgery, as observed in the control group. In the rat uterine horn adhesion model, SI-449 reduced the adhesion frequency to 40%, compared with 100% in the control.
CONCLUSIONS: SI-449 exhibits anti-adhesion activity in animal models of postoperative adhesion. The mechanism of action of SI-449 during wound healing suggests mechanical obstruction of fibrin net structure formation, which is a key step in the development of adhesions at surgical sites. SI-449 is a promising candidate for preventing postoperative adhesions in clinical practice.

Keywords:  Adhesion prevention; Bioresorbable barrier; Chondroitin sulfate; Cross-linking technology; Postoperative adhesion

DOI:  https://doi.org/10.1016/j.jss.2024.10.016
Int J Mol Sci. 2024 Nov 04. pii: 11822. [Epub ahead of print]25(21):

Inhibition of Cancer Cell Migration and Invasion In Vitro by Recombinant Tyrosine-Sulfated Haemathrin, A Thrombin Inhibitor.

Guk Heui Jo, Sun Ah Jung, Jin Sook Yoon, Joon H Lee.

  Thrombin, a key enzyme in the regulation of hemostasis, has been implicated in cancer progression. This study explored the effect of recombinant tyrosine-sulfated haemathrin on cancer cell behavior and signaling pathways compared to wild-type (WT) haemathrin 2. The recombinant proteins, tyrosine-sulfated haemathrin 2 (haemathrin 2S), and WT haemathrin 2 were produced in Escherichia coli and subsequently purified and applied to SKOV3 and MDA-MB-231 cells with and without thrombin stimulation. Cell migration and invasion were assessed using wound healing and Transwell assays, respectively. Haemathrin 2S treatment significantly diminished cell migration and invasion promoted by thrombin in both SKOV3 and MDA-MB-231 cells (p < 0.05). Additionally, haemathrin 2S effectively inhibited thrombin-induced phosphorylation of serine/threonine kinase (Akt) in both cell lines (p < 0.05), while WT haemathrin 2 had this effect only in MDA-MB-231 cells. Furthermore, haemathrin 2S significantly reduced thrombin-activated phosphorylation of extracellular signal-regulated kinases (ERK) and p38 in both cell lines (p < 0.05) and reversed E/N-cadherin expression in thrombin-treated MDA-MB-231 cells (p < 0.05), which were not observed with WT haemathrin 2. Overall, haemathrin 2S was more effective than WT haemathrin 2 in reducing cancer cell migration and invasion, indicating that targeting thrombin with sulfated haemathrin is a promising strategy for cancer therapy. However, further in vivo studies are needed to confirm these results.

Keywords:  cancer; epithelial–mesenchymal transition; invasion; madanin-1; metastasis; migration; sulfated haemathrin; thrombin; tyrosine sulfation

DOI:  https://doi.org/10.3390/ijms252111822
J Med Life. 2024 Aug;17(8): 791-799

Reducing the levels of indoxyl sulfate in patients undergoing dialysis: a promising approach to managing inflammation and the redox state of human serum albumin.

Wesam Ahmed Nasif, Mohammed Hassan Mokhtar, Ashraf Abdelazeem Ewis, Hiba Saeed Al-Amodi, Abeer Shaker El Moursy Ali.

  Indoxyl sulfate (IS) is one of the most potent uraemic toxins involved in the progression of chronic kidney disease (CKD) through the induction of inflammation and oxidative stress. This study assessed the potential benefits of reducing IS concentrations through dialysis treatment to improve renal function, inflammation, and oxidative stress. A prospective, observational cohort study of 50 patients with CKD undergoing dialysis treatment was conducted. IS levels, inflammatory markers (IL-6 and hs-CRP), and oxidative status (Cu/Zn-SOD) were measured using immunoenzymatic methods, and the albumin ratio (HNA/HMA) was assessed using high-performance liquid chromatography. Blood samples were collected at baseline and, at 8 weeks and 16 weeks after treatment. At baseline, patients with CKD had elevated levels of IS, renal function indicators, inflammatory markers (IL-6 and CRP), and oxidative markers (Cu/Zn-SOD and albumin ratio HNA/HMA). Dialysis treatment reduced IS levels, and a correlation among IS, renal function, and SOD levels (P < 0.0001) at 8 and 16 weeks was observed. The reduction in IS levels was associated with improved inflammatory marker levels (CRP and IL-6; P < 0.0001) and a significant decrease in the HNA/HMA ratio (P <0.0001) at 8 and 16 weeks. These associations strengthened over time. The results of this study suggest that IS levels may be a therapeutic target for improving outcomes in patients with CKD by improving renal function, inflammation, and oxidative stress. More research is needed to understand how IS contributes to CKD complications.

Keywords:  chronic kidney disease (CKD); indoxyl sulfate; inflammatory markers; oxidized albumin

DOI:  https://doi.org/10.25122/jml-2023-0538
Commun Biol. 2024 Nov 08. 7(1): 1471

Sulfated galactofucan from Sargassum fusiforme protects against postmenopausal osteoporosis by regulating bone remodeling.

Bao Yizhong, Fen Chen, Weihua Jin, Jihua Dai, Genxiang Mao, Boshan Song.

Osteoporosis is a degenerative bone disease highly prevalent in older women, causing high morbidity and mortality rates. Fourteen kinds of fucoidan were isolated from Sargassum fusiforme through acid (named as SFS), alkaline (SFJ) and water (SFW). SFW was passed through an anion exchange column to obtain SFW-0, SFW-0.5 and SFW-2. SFW-0.5 and SFW-2 were degraded to obtain different sulfate group contents SFW-x-M/S/O (x for 0.5 or 2). We further confirmed SFW-0.5-O was the most effective fraction of SFW. SFW-0.5-O may have alternating backbones of (Gal)n and (Fuc)n, and the main sulfation may be at C2/C3 of the Fuc/Gal residues. SFW-0.5-O inhibition of OC differentiation was associated with IRF-8 signaling; meanwhile, SFW-0.5-O promoted osteoblast differentiation and bone mineral nodule formation. SFW-0.5-O also effectively ameliorated osteoporosis symptom caused by estrogen deprivation in vivo. We uncovered that the fucoidan active fraction SFW-0.5-O demonstrated effective bone protection, may be exploited for osteoporosis therapy.

DOI: https://doi.org/10.1038/s42003-024-07097-2
Glob Chall. 2024 Nov;8(11): 2400083

Structural, Functional, and Bioactive Properties of Sulfated Polysaccharides from Skipjack Tuna Skin as a Function of Drying Techniques.

Shahab Naghdi, Masoud Rezaei, Mehdi Alboofetileh, Mehdi Tabarsa, Mehdi Abdollahi, Jamshid Amiri Moghaddam.

  The study aims to investigate the impact of various drying techniques on the quality of sulfated polysaccharides (SP) extracted from Skipjack tuna (Katsuwonus pelamis) skin. Three drying methods, namely microwave drying (M-KPP), freeze-drying (F-KPP), and hot air drying (HA-KPP), are examined. The chemical and monosaccharide compositions of SP are significantly affected by the drying methods. The extraction yields for M-KPP, F-KPP, and HA-KPP are 3.30%, 3.11%, and 2.50%, respectively (P < 0.05). Additionally, HA-KPP, with 10.67% moisture content, exhibits the lowest moisture level among the dried samples (P < 0.05). Furthermore, the structural properties of SP remain consistent across different drying methods, as indicated by FTIR, XRD, and DSC analyses. F-KPP demonstrates the highest antioxidant properties. The functional and antimicrobial activities of SP are significantly influenced by the drying technique, with hot air drying resulting in increased foaming capacity and microwave drying showing enhanced antimicrobial activity. In conclusion, the findings demonstrate that the functionality and bioactivity of SP from tuna skin are greatly influenced by the drying technique employed, suggesting that the selection of the optimal method should be tailored to the desired properties of the SPs and given careful consideration.

Keywords:  Katsuwonus pelamis; antibacterial properties; antioxidant activities; drying methods; sulfated polysaccharides

DOI:  https://doi.org/10.1002/gch2.202400083
Dis Model Mech. 2024 Nov 07. pii: dmm.052107. [Epub ahead of print]

Slc26a2-mediated sulfate metabolism is significant for the tooth development.

Y Yoshida, T Inubushi, M Yokoyama, P Nag, J I Sasaki, A Oka, T Murotani, R Kani, Y Shiraishi, H Kurosaka, Y Takahata, R Nishimura, S Imazato, P Papagerakis, T Yamashiro.

  The sulfate transporter gene SLC26A2 is crucial for skeletal formation, as evidenced by its role in diastrophic dysplasia, a type of skeletal dysplasia in humans. While SLC26A2-related chondrodysplasia also affects craniofacial and tooth development, its specific role in these processes remains unclear. In this study, we explore the pivotal roles of SLC26A2-mediated sulfate metabolism during tooth development. We found that Slc26a2 is predominantly expressed in dental tissues, including odontoblasts and ameloblasts. Slc26a2 knockout mice (Slc26a2-KO-Δexon2) exhibit distinct craniofacial abnormalities, such as a retrognathic upper jaw, small upper incisors, and upper molar hypoplasia. These mice also show flattened odontoblasts and loss of nuclear polarity in upper incisors and molars, with significant reductions in odontoblast differentiation markers Dspp and Dmp1. Ex vivo and in vitro studies further reveal dentin matrix hypoplasia, tooth root shortening, and downregulation of Wnt signaling in Slc26a2-deficient cells. These findings highlight the significant role of SLC26A2-mediated sulfate metabolism in tooth development and offer insights into the mechanisms underlying dental abnormalities in patients with SLC26A2-related chondrodysplasias.

Keywords:  Extracellular matrix (ECM); Matrix biology; Odontoblasts; SLC26A2; Sulfate metabolism; Tooth development

DOI:  https://doi.org/10.1242/dmm.052107
Elife. 2024 Nov 08. pii: RP99000. [Epub ahead of print]13

Heparan sulphate binding controls in vivo half-life of the HpARI protein family.

Florent Colomb, Abhishek Jamwal, Adefunke Ogunkanbi, Tania Frangova, Alice R Savage, Sarah Kelly, Gavin J Wright, Matthew K Higgins, Henry J McSorley.

  The parasitic nematode Heligmosomoides polygyrus bakeri secretes the HpARI family, which bind to IL-33, either suppressing (HpARI1 and HpARI2) or enhancing (HpARI3) responses to the cytokine. We previously showed that HpARI2 also bound to DNA via its first complement control protein (CCP1) domain. Here, we find that HpARI1 can also bind DNA, while HpARI3 cannot. Through the production of HpARI2/HpARI3 CCP1 domain-swapped chimeras, DNA-binding ability can be transferred, and correlates with in vivo half-life of administered proteins. We found that HpARI1 and HpARI2 (but not HpARI3) also binds to the extracellular matrix component heparan sulphate (HS), and structural modelling showed a basic charged patch in the CCP1 domain of HpARI1 and HpARI2 (but not HpARI3) which could facilitate these interactions. Finally, a mutant of HpARI2 was produced which lacked DNA and HS binding, and was also shown to have a short half-life in vivo. Therefore, we propose that during infection the suppressive HpARI1 and HpARI2 proteins have long-lasting effects at the site of deposition due to DNA and/or extracellular matrix interactions, while HpARI3 has a shorter half-life due to a lack of these interactions.

Keywords:  Heligmosoides polygyrus bakeri; IL-33; heparan sulphate; immunology; infectious disease; inflammation; microbiology; mouse

DOI:  https://doi.org/10.7554/eLife.99000