bims-supasi 2022-11-13 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2022–11–13
thirteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Chondroitin sulfate-based composites: a tour d'horizon of their biomedical applications.
Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases.
Revisiting the physiological role of androgens in women.
Hungatella hathewayi, an Efficient Glycosaminoglycan-Degrading Firmicutes from Human Gut and Its Chondroitin ABC Exolyase with High Activity and Broad Substrate Specificity.
Chondroitin Sulfate-Derived Paclitaxel Nanocrystal via π-π Stacking with Enhanced Stability and Tumor Targetability.
Serum levels of dehydroepiandrosterone sulfate are associated with a lower risk of mobility-subtype frailty in older Japanese community-dwellers.
Early Changes in Androgen Levels in Individuals with Spinal Cord Injury: A Longitudinal SwiSCI Study.
Gut microbiota involved in desulfation of sulfated progesterone metabolites: A potential regulation pathway of maternal bile acid homeostasis during pregnancy.
Plasma and Urine Levels of Glycosaminoglycans in Patients with Systemic Sclerosis and Their Relationship to Selected Interleukins and Marker of Early Kidney Injury.
Phytochemistry Meets Geochemistry-Blumenol C Sulfate: A New Megastigmane Sulfate from Palicourea&nbsp;luxurians (Rubiaceae: Palicoureeae).
Characterization and bioactivity analysis of a heteropolysaccharide purified from Paenibacillus edaphicus strain UJ1.
The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins.
Characterization of Vascular Patterns Associated with Endothelial Glycocalyx Damage in Early- and Late-Onset Preeclampsia.

J Mater Chem B. 2022 Nov 07.

Chondroitin sulfate-based composites: a tour d'horizon of their biomedical applications.

Mohammed A S Abourehab, Shreya Baisakhiya, Akanksha Aggarwal, Anshul Singh, Mohamed A Abdelgawad, A Deepak, Mohammad Javed Ansari, Sheersha Pramanik.

Chondroitin sulfate (CS), a natural anionic mucopolysaccharide, belonging to the glycosaminoglycan family, acts as the primary element of the extracellular matrix (ECM) of diverse organisms. It comprises repeating units of disaccharides possessing β-1,3-linked N-acetyl galactosamine (GalNAc), and β-1,4-linked D-glucuronic acid (GlcA), and exhibits antitumor, anti-inflammatory, anti-coagulant, anti-oxidant, and anti-thrombogenic activities. It is a naturally acquired bio-macromolecule with beneficial properties, such as biocompatibility, biodegradability, and immensely low toxicity, making it the center of attention in developing biomaterials for various biomedical applications. The authors have discussed the structure, unique properties, and extraction source of CS in the initial section of this review. Further, the current investigations on applications of CS-based composites in various biomedical fields, focusing on delivering active pharmaceutical compounds, tissue engineering, and wound healing, are discussed critically. In addition, the manuscript throws light on preclinical and clinical studies associated with CS composites. A short section on Chondroitinase ABC has also been canvassed. Finally, this review emphasizes the current challenges and prospects of CS in various biomedical fields.

DOI: https://doi.org/10.1039/d2tb01514e
Int J Mol Sci. 2022 Oct 29. pii: 13146. [Epub ahead of print]23(21):

Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases.

Joanne K Tobacman, Sumit Bhattacharyya.

  The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). The newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. The regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

Keywords:  Arylsulfatase B; N-acetylgalactosamine-4-sulfatase; Warburg effect; chondroitin 4-sulfate; cystic fibrosis; dermatan sulfate; malignancy; mucopolysaccharidosis; proteoglycans; sulfated glycosaminoglycans

DOI:  https://doi.org/10.3390/ijms232113146
Expert Rev Endocrinol Metab. 2022 Nov 09. 1-15

Revisiting the physiological role of androgens in women.

Elena Rosato, Francesca Sciarra, Eleni Anastasiadou, Andrea Lenzi, Mary Anna Venneri.

   INTRODUCTION: Extensive research underlines the critical functions of androgens in females. Nevertheless, the precise mechanisms of their action are poorly understood. Here, we review the existing literature regarding the physiological role of androgens in women throughout life.
AREAS COVERED: Several studies show that androgen receptors (ARs) are broadly expressed in numerous female tissues. They are essential for many physiological processes, including reproductive, sexual, cardiovascular, bone, muscle, and brain health. They are also involved in adipose tissue and liver function. Androgen levels change with the menstrual cycle and decrease in the first decades of life, independently of menopause.
EXPERT OPINION: To date, studies are limited by including small numbers of women, the difficulty of dosing androgens, and their cyclical variations. In particular, whether androgens play any significant role in regulating the establishment of pregnancy is poorly understood. The neural functions of ARs have also been investigated less thoroughly, although it is expressed at high levels in brain structures. Moreover, the mechanism underlying the decline of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with age is unclear. Other factors, including estrogen's effect on adrenal androgen production, reciprocal regulation of ARs, and non-classical effects of androgens, remain to be determined.

Keywords:  Androgens; female physiology; fertility; hormones regulation; reproduction

DOI:  https://doi.org/10.1080/17446651.2022.2144834
Appl Environ Microbiol. 2022 Nov 07. e0154622

Hungatella hathewayi, an Efficient Glycosaminoglycan-Degrading Firmicutes from Human Gut and Its Chondroitin ABC Exolyase with High Activity and Broad Substrate Specificity.

Parkash Singh Rawat, Yan Li, Weixin Zhang, Xiangfeng Meng, Weifeng Liu.

  The degradation of glycosaminoglycans (GAGs) by intestinal bacteria is critical for their colonization in the human gut and the health of the host. Both colonic Bacteroides and Firmicutes have been reported to degrade GAGs; however, the enzymatic details of the latter remain largely unknown. Our bioinformatic analyses of fecal Firmicutes revealed that their genomes, especially Hungatella hathewayi strains, are an abundant source of putative GAG-specific catabolic enzymes. Subsequently, we isolated a Firmicutes strain, H. hathewayi N2-326, that can catabolize various GAGs. While H. hathewayi N2-326 was as efficient in utilizing chondroitin sulfate A (CSA) and dermatan sulfate as Bacteroides thetaiotaomicron, a well-characterized GAG degrader, it outperformed B. thetaiotaomicron in assimilating hyaluronic acid. Unlike B. thetaiotaomicron, H. hathewayi N2-326 could not utilize heparin. The chondroitin lyase activity of H. hathewayi N2-326 was found to be present predominantly in the culture supernatant. Genome sequence analysis revealed three putative GAG lyases, but only the HH-chondroitin ABC lyase was upregulated in the presence of CSA. In addition, five CAZyme gene clusters containing GAG metabolism genes were significantly upregulated when grown on CSA. Further characterization of the recombinant HH-chondroitin ABC lyase revealed that it cleaves GAGs predominantly in an exo-mode to produce unsaturated disaccharides as the primary hydrolytic product while exhibiting a higher specific activity than reported chondroitin ABC lyases. HH-chondroitin ABC lyase represents the first characterized chondroitin lyase from intestinal Firmicutes and offers a viable commercial option for the production of chondroitin, dermatan, and hyaluronan oligosaccharides and also for potential medical applications. IMPORTANCE An increased understanding of GAG metabolism by intestinal bacteria is critical in identifying the driving factors for the composition, modulation, and homeostasis of the human gut microbiota. In addition, GAG-depolymerizing polysaccharide lyases are highly desired enzymes for the production of GAG oligosaccharides and as therapeutics. At present, the dissection of the enzymatic machinery for GAG degradation is highly skewed toward Bacteroides. In this study, we have isolated an efficient GAG-degrading Firmicutes bacterium from human feces and characterized the first chondroitin ABC lyase from a Firmicutes, which complements the fundamental knowledge of GAG utilization in the human colon. The genomic and transcriptomic analysis of the bacterium shows that Firmicutes might use a distinct approach to catabolize GAGs from that used by Bacteroides. The high specific activity of the characterized chondroitin ABC lyase aids future attempts to develop a commercial chondroitinase for industrial and medicinal applications.

Keywords:  Bacteroides; Firmicutes; Hungatella hathewayi; chondroitin ABC lyase; glycosaminoglycans

DOI:  https://doi.org/10.1128/aem.01546-22
ACS Appl Mater Interfaces. 2022 Nov 09.

Chondroitin Sulfate-Derived Paclitaxel Nanocrystal via π-π Stacking with Enhanced Stability and Tumor Targetability.

Dandan Huang, Jiajia Gui, Xue Chen, Ruilian Yu, Tao Gong, Zhirong Zhang, Yao Fu.

  Nanocrystals with high drug loading have become a viable strategy for solubilizing drugs with poor aqueous solubility. It remains challenging, however, to synthesize nanocrystals with sufficient stability and targeting potential. Here, we report a novel nanocrystal platform synthesized using paclitaxel (PTX) and Fmoc-8-amino-3,6-dioxaoctanoic acid (Fmoc-AEEA)-conjugated chondroitin sulfate (CS) (CS-Fmoc) via π-π stacking to afford a stable formulation with CD44 targetability (PTX NC@CS-Fmoc). The PTX NC@CS-Fmoc exhibited rodlike shapes with an average hydrodynamic size of 173.6 ± 0.7 nm (PDI = 0.11 ± 0.04) and a drug loading of up to 31.3 ± 0.6%. Next, PTX NC@CS-Fmoc was subjected to lyophilization in the absence of cryoprotectants for long-term storage, and after redispersion, PTX NC@CS-Fmoc displayed an average hydrodynamic size of 205.3 ± 2.9 nm (PDI = 0.15 ± 0.01). In murine Panc02 cells, PTX NC@CS-Fmoc showed higher internalization efficiency than that of PTX nanocrystals without CS modification (PTX NC@F127) (P < 0.05) or that of CS-Fmoc micelles (P < 0.05). Moreover, PTX NC@CS-Fmoc appeared to accumulate in both lysosomes and Golgi apparatus, while CS-Fmoc micelles accumulated specifically in the Golgi apparatus. In the orthotopic Panc02 tumor-bearing mice model, PTX NC@CS-Fmoc showed higher tumor-specific accumulation than CS-Fmoc micelles, which also demonstrated comparable tumor growth inhibition as to Nab-PTX. Overall, the CS-Fmoc-derived nanocrystals represent a neat and viable formulation strategy for targeted chemotherapy with great potential for translational studies.

Keywords:  chondroitin sulfate; nanocrystal; paclitaxel; pancreatic cancer; π−π stacking

DOI:  https://doi.org/10.1021/acsami.2c15881
Arch Gerontol Geriatr. 2022 Oct 23. pii: S0167-4943(22)00233-3. [Epub ahead of print]105 104846

Serum levels of dehydroepiandrosterone sulfate are associated with a lower risk of mobility-subtype frailty in older Japanese community-dwellers.

Shu Zhang, Rei Otsuka, Hiroshi Shimokata, Yukiko Nishita, Chikako Tange, Marie Takemura, Shosuke Satake.

   PURPOSE: Previous studies suggest that lower serum levels of dehydroepiandrosterone sulfate (DHEA-S) are associated with physical frailty. Associations with subtypes of physical frailty have not been studied. This study aimed to investigate associations between serum DHEA-S levels and physical frailty and its subtypes in older Japanese community-dwellers using panel data.
METHODS: This study was conducted within the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). Repeated measurement data were collected from 1,886 older community-dwellers (60-91 years). Frailty was identified according to modified Cardiovascular Health Study criteria (weight loss, weakness, slowness, exhaustion, low physical activity) and was classified into following subtypes: mobility (weakness/slowness), non-mobility (weight loss/exhaustion), and low physical activity. Associations with serum DHEA-S (sex-specific tertiles [T1-T3]) were estimated by random-effects logistic regression models adjusting for age, sex, education, disease history (stroke, hypertension, heart disease, diabetes), smoking status, depressive symptoms, and survey wave.
RESULTS: We found an average prevalence of 6.0% for frailty (mobility subtype, 7.0%; non-mobility subtype, 34.8%; low physical activity subtype, 9.4%) across survey waves. Mean (SD) sex-specific DHEA-S levels (μg/dL) at T1, T2, and T3 were 46.8 (20.8), 88.7 (28.4), and 158.0 (58.9), respectively. Compared with T1, the adjusted ORs (95% CIs) for frailty were 0.69 (0.44, 1.08) for T2 and 0.50 (0.30, 0.83) for T3 (P trend = 0.007). The corresponding values for mobility subtype were 0.80 (0.51, 1.24) for T2 and 0.55 (0.33, 0.90) for T3.
CONCLUSION: Higher serum DHEA-S levels were associated with lower risk of frailty, especially mobility-subtype frailty, in older community-dwellers.

Keywords:  Dehydroepiandrosterone sulfate; Physical frailty; Subtypes

DOI:  https://doi.org/10.1016/j.archger.2022.104846
J Clin Med. 2022 Nov 04. pii: 6559. [Epub ahead of print]11(21):

Early Changes in Androgen Levels in Individuals with Spinal Cord Injury: A Longitudinal SwiSCI Study.

Oche Adam Itodo, Peter Francis Raguindin, Jens Wöllner, Inge Eriks-Hoogland, Xavier Jordan, Margret Hund-Georgiadis, Taulant Muka, Jürgen Pannek, Jivko Stoyanov, Marija Glisic.

  We aimed to explore longitudinal changes in androgen levels in individuals with spinal cord injury (SCI) within initial inpatient rehabilitation stay and identify clinical/injury characteristics associated with hormone levels. Linear regression analysis was applied to explore the association between personal/injury characteristics and androgen hormones (total testosterone, free testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S)) at admission to rehabilitation. Longitudinal changes in androgen levels were studied using linear mixed models. Analyses were stratified by sex and by injury type. We included 70 men and 16 women with SCI. We observed a non-linear association between age, time since injury, and androgens at baseline. At admission to initial rehabilitation, mature serum SHBG (full-length, protein form which lacks the N-terminal signaling peptide) was higher, while DHEA and DHEA-S were lower among opioid users vs. non-users. Serum levels of total testosterone and DHEA-S increased over rehabilitation period [β 3.96 (95%CI 1.37, 6.56), p = 0.003] and [β 1.77 (95%CI 0.73, 2.81), p = 0.01], respectively. We observed no significant changes in other androgens. Restricting our analysis to men with traumatic injury did not materially change our findings. During first inpatient rehabilitation over a median follow up of 5.6 months, we observed an increase in total testosterone and DHEA-S in men with SCI. Future studies need to explore whether these hormonal changes influence neurological and functional recovery as well as metabolic parameters during initial rehabilitation stay.

Keywords:  androgens; dehydroepiandrosterone; dehydroepiandrosterone sulfate; rehabilitation; sex hormone-binding globulin; spinal cord injury; testosterone

DOI:  https://doi.org/10.3390/jcm11216559
Front Microbiol. 2022 ;13 1023623

Gut microbiota involved in desulfation of sulfated progesterone metabolites: A potential regulation pathway of maternal bile acid homeostasis during pregnancy.

Peng Wang, Qianqian Chen, Peiqiang Yuan, Sen Lin, Hong Chen, Ran Li, Xiaoling Zhang, Yong Zhuo, Jian Li, Lianqiang Che, Bin Feng, Yan Lin, Shengyu Xu, De Wu, Zhengfeng Fang.

  Abnormally raised circulating bile acids (BA) during pregnancy threat fetal and offspring health. Our previous study has identified sulfated progesterone metabolites (PMSs) in part account for dysregulation of maternal BA homeostasis during pregnancy, however, limited intervention strategies to remedy increased serum BA through PMSs during pregnancy are available. The purpose of this study is to test the feasibility of manipulating BA homeostasis and progesterone metabolism through steering gut microbiota. A total of 19 pregnant sows were randomly treated with standard diet or vancomycin-supplemented diet, to investigate the intercorrelation of PMSs, intestinal microbiota, and maternal BA metabolism from day 60 of gestation (G60) until farrowing (L0). Pregnant mice orally gavaged with epiallopregnanolone sulfate (PM5S) or vehicle and nonpregnant mice were sampled and further analyzed to verify the effect of PM5S on maternal BA metabolism. The present study revealed that oral vancomycin reduced maternal fasting serum total BA (TBA) levels and postprandial serum TBA levels at day 90 of gestation (G90). BA profile analysis showed the decreased TBA after vancomycin treatment was attributed to the decrease of primary BA and secondary BA, especially hyodeoxycholic acid (HDCA). By using newly developed UPLC-MS/MS methods, we found vancomycin increased fecal excretion of allopregnanolone sulfate (PM4S) and PM5S during late gestation and thus maintaining the relative stability of serum PM4S and PM5S, which play an important role in BA metabolism. Further study in mice showed that pregnant mice have higher serum and liver TBA levels compared with nonpregnant mice, and PM5S administration induced higher gallbladder TBA levels and TBA pool in pregnant mice. In addition, after oral vancomycin, the continuously decreased Parabacteroides genus, potentially enriched with genes encoding steroids sulfatase, may explain the increased fecal PMSs excretion in pregnant sows. Taken together, our study provides the evidence that pregnancy-induced elevation of BA levels in sow is likely regulated by manipulation of gut microbiota, which offer new insights into the prevention and treatment of disrupted BA homeostasis during pregnancy by targeting specific microbiota.

Keywords:  bile acid homeostasis; gut microbiota; pregnant sows; sulfated progesterone metabolites; vancomycin

DOI:  https://doi.org/10.3389/fmicb.2022.1023623
J Clin Med. 2022 Oct 27. pii: 6354. [Epub ahead of print]11(21):

Plasma and Urine Levels of Glycosaminoglycans in Patients with Systemic Sclerosis and Their Relationship to Selected Interleukins and Marker of Early Kidney Injury.

Kornelia Kuźnik-Trocha, Katarzyna Winsz-Szczotka, Katarzyna Komosińska-Vassev, Agnieszka Jura-Półtorak, Adrian Miara, Przemysław Kotyla, Krystyna Olczyk.

  Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by immune system dysfunction, vasculopathy, and progressive fibrosis of the skin and internal organs, resulting from excessive accumulation of extracellular matrix (ECM) elements, including collagen and proteoglycans (PGs). An uncontrolled PG proliferation, caused by disturbances in their metabolism in tissues, is most likely reflected in the quantitative changes of their components, i.e., glycosaminoglycans (GAGs), in body fluids. Therefore, the aim of this study was to quantify the different types of GAGs in the blood and urine of systemic sclerosis patients. Chondroitin/dermatan sulfates (CS/DS) and heparan sulfates/heparin (HS/H) were quantified by hexuronic acid assay and electrophoretic fractionation, while hyaluronic acid (HA) and keratan sulfates were evaluated using ELISA tests. In turn, individual urinary GAGs were determined using the Blyscan™ Sulfated Glycosaminoglycan Assay Kit. Our results showed that the plasma concentrations of CS/DS, HS/H, HA, and KS in systemic sclerosis patients were significantly higher compared with those in healthy subjects. In the case of urine measurements, we have found that in SSc patients, CS/DC concentrations were significantly higher, while HA concentrations were significantly lower compared with the values observed in the urine of healthy subjects. Importantly, the found by us correlations between plasma keratan sulfate levels and both the duration of the disease and the severity of skin lesions, as expressed by the Rodnan scale, seems to suggest this GAG as a potential marker in assessing disease progression and activity. In addition, a level of urinary excretion of all types of GAGs due to their high positive correlation with uACR, may be a valuable complementary test in the diagnosis of early renal dysfunction in the course of SSc.

Keywords:  chondroitin/dermatan sulfates; glycosaminoglycans; heparan sulfates/heparin; hyaluronic acid; interleukin 17; interleukin 18; keratan sulfates; systemic sclerosis

DOI:  https://doi.org/10.3390/jcm11216354
Molecules. 2022 Oct 26. pii: 7284. [Epub ahead of print]27(21):

Phytochemistry Meets Geochemistry-Blumenol C Sulfate: A New Megastigmane Sulfate from Palicourea&nbsp;luxurians (Rubiaceae: Palicoureeae).

Christoph Kornpointner, Nadine J Hochenegger, Bao-Bao Shi, Andreas Berger, Johannes Theiner, Lothar Brecker, Johann Schinnerl.

  There is a previously neglected influence of geochemical conditions on plant phytochemistry. In particular, high concentrations of dissolved salts can affect their biosynthesis of natural products. Detoxification is most likely an important aspect for the plant, but additional natural products can also give it an expanded range of bioactivities. During the phytochemical analysis a Palicourea luxurians plant collected in a sulfate-rich environment (near the Río Sucio, Costa Rica) showed an interesting natural product in this regard. The structure of this compound was determined using spectroscopic and computational methods (NMR, MS, UV, IR, CD, optical rotation, quantum chemical calculations) and resulted in a megastigmane sulfate ester possessing a β-ionone core structure, namely blumenol C sulfate (1, C13H22O5S). The levels of sulfur and sulfate ions in the leaves of the plant were determined using elemental analysis and compared to the corresponding levels in comparable plant leaves from a less sulfate-rich environments. The analyses show the leaves from which we isolated blumenol C sulfate (1) to contain 35% more sulfur and 80% more sulfate than the other samples. Antimicrobial and antioxidant activities of compound 1 were tested against Escherichia coli, E. coli ampR and Bacillus subtilis as well as measured using complementary in vitro FRAP and ATBS assays, respectively. These bioactivities are comparable to those determined for structurally related megastigmanes. The sulfur and sulfate content of the plant leaves from the sulfate-rich environment was significantly higher than that of the other plants. Against this background of salt stress, we discuss a possible biosynthesis of blumenol C sulfate (1). Furthermore, there appears to be no benefit for the plant in terms of extended bioactivities. Hence, the formation of blumenol C sulfate (1) probably primarily serves the plant detoxification process.

Keywords:  Palicourea luxurians; Rubiaceae; Río Sucio; blumenol C sulfate; elemental analysis; megastigmane

DOI:  https://doi.org/10.3390/molecules27217284
Int J Biol Macromol. 2022 Nov 05. pii: S0141-8130(22)02559-4. [Epub ahead of print]223(Pt A): 57-66

Characterization and bioactivity analysis of a heteropolysaccharide purified from Paenibacillus edaphicus strain UJ1.

Deyao Meng, Hongyang Wang, Baocai Song, Huijuan Zhang, Renjie Fu, Shiming Wang, Jing Li, Jianfa Zhang.

  Many polysaccharides produced by Paenibacillus spp. have attractive properties, such as rheological modification and immunomodulation. However, properties of P. edaphicus polysaccharides are not understood sufficiently. Here, the polysaccharide (PUM) was obtained from P. edaphicus strain UJ1 by batch fermentation, and the chemical characteristics, rheological and anti-inflammatory properties of PUM and its sulfate derivative (PUM-S) were investigated. The results indicated that PUM was a typical shear-thinning biopolymer with an estimated weight average molecular weight of 2.45 × 107 Da. PUM molecule consisted of D-Man, D-GlcA, D-Glc, D-Gal, and L-Fuc with the molar ratio of 3.00:1.07:3.21:0.81:0.76. It had the backbone → 3)-β-D-Man-(1 → 3)-β-D-Glc-(1 → 3)-β-D-Man-(1 → 3)β-D-Glc-(1 → 4)-β-D-GlcA-(1 → 3)-β-D-Man-(1 → and two side chains, namely, pyruvoyl-Glc-(1→ and β-L-Fuc-(1 → 3)-β-D-Gal-(1→. Moreover, PUM-S was prepared by SO3-pyridine method and had the weight average molecular weight of 1.42 × 105 Da. The bioactivity of PUM and PUM-S was analyzed in vitro in RAW 264.7 cells. The results indicated that both PUM and PUM-S facilitated cell proliferation at 50-500 μg/mL. Besides, PUM-S showed potential anti-inflammatory effect in the LPS-induced cells. According to transcription and molecular dynamics analyses, PUM-S expressed its activity probably by interacting with the Toll-like receptor 4. In general, P. edaphicus produced a polysaccharide with new chemical structure and promising rheological and bioactive properties.

Keywords:  Anti-inflammation; Paenibacillus edaphicus; Polysaccharide; Rheology; Structure; Sulfation

DOI:  https://doi.org/10.1016/j.ijbiomac.2022.11.016
Toxins (Basel). 2022 Nov 10. pii: 779. [Epub ahead of print]14(11):

The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins.

Yang Gyun Kim, Sang Ho Lee, Su Woong Jung, Gun Tae Jung, Hyun Ji Lim, Kwang Pyo Kim, Young-Il Jo, KyuBok Jin, Ju Young Moon.

  The accumulation of protein-bound uremic toxins (PBUT) is associated with increased cardiovascular outcomes in patients on dialysis. However, the efficacy of PBUT removal for a medium-cutoff (MCO) membrane has not been clarified. This study was designed to assess the efficacy of PBUT clearance according to dialysis modalities. In this prospective and cross-over study, we enrolled 22 patients who received maintenance hemodiafiltration (HDF) thrice weekly from three dialysis centers. The dialysis removal of uremic toxins, including urea, beta 2-microglobulin (B2MG), lambda free light chain (λ-FLC), indoxyl sulfate (IS), and p-cresyl sulfate (pCS), was measured in the 22 patients on high-flux HD (HF-HD), post-dilution online HDF (post-OL-HDF), and MCO-HD over 3 weeks. The average convection volume in post-OL-HDF was 21.4 ± 1.8 L per session. The reduction rate (RR) of B2MG was higher in post-OL-HDF than in MCO-HD and HF-HD. The RR of λ-FLC was the highest in MCO-HD, followed by post-OL-HDF and HF-HD. The dialysate albumin was highest in MCO-HD, followed by post-OL-HDF and HF-HD. Post-dialysis plasma levels of IS and pCS were not statistically different across dialysis modalities. The total solute removal and dialytic clearance of IS and pCS were not significantly different. The clearance of IS and pCS did not differ between the HF-HD, post-OL-HDF, and MCO-HD groups.

Keywords:  hemodiafiltration; indoxyl sulfate; medium-cutoff; p-cresyl sulfate; protein-bound uremic toxin

DOI:  https://doi.org/10.3390/toxins14110779
Biomedicines. 2022 Nov 02. pii: 2790. [Epub ahead of print]10(11):

Characterization of Vascular Patterns Associated with Endothelial Glycocalyx Damage in Early- and Late-Onset Preeclampsia.

Marina M Ziganshina, Kamilla T Muminova, Nailia R Khasbiullina, Zulfiya S Khodzhaeva, Ekaterina L Yarotskaya, Gennady T Sukhikh.

  This paper provides an assessment of molecular and functional changes in blood vessels, and a description of vascular patterns during preeclampsia (PE). Patients with normal pregnancy, and pregnancy complicated by PE at earlier (20-34 weeks) and later terms (≥34 weeks) underwent a 24 h monitoring of blood pressure, central hemodynamics, arterial stiffness, and myocardial function. The blood levels of the structural components of endothelial glycocalyx (eGC): syndecan-1 (SDC 1), heparan sulfate proteoglycan 2 (HSPG2), and hyaluronic acid (HA) were determined. In early-onset PE, the vascular pattern comprised changes in all structural components of eGCs, including transmembrane proteoglycans levels, and severe disorders of central hemodynamics, arterial stiffness, and myocardial changes, probably leading to more severe course of PE and the formation of morphological grounds for cardiovascular disorders. The vascular pattern in late-onset PE, including changes in HA levels, central hemodynamics, and myocardial function, may be a signal of potential cardiovascular disorder. PE may change adaptive hemodynamic responses to a pathological reaction affecting both arterial elasticity and the left ventricular myocardium, with its subsequent hypertrophy and decompensation, leading to a delayed development of cardiovascular disorders after PE. Further clinical studies of these indicators will possibly identify predictors of PE and long-term consequences of the disease.

Keywords:  BPLab 24 h blood pressure monitoring; early-onset preeclampsia; endothelial glycocalyx; heparan sulfate proteoglycans (HSPGs); hyaluronic acid (HA); late-onset preeclampsia; pregnancy; syndecan 1 (SDC 1); vascular patterns

DOI:  https://doi.org/10.3390/biomedicines10112790