bims-supasi 2023-08-06 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2023–08–06
eight papers selected by
Jonathan Wolf Mueller, University of Birmingham

Sulfated and non-sulfated chondroitin affect the composition and metabolism of human colonic microbiota simulated in an in vitro fermentation system.
Evaluation of effects of indoxyl sulfate and parathyroid hormone on CYP3A activity considering the influence of CYP3A5 gene polymorphisms.
A spectroscopic response factor-based toluidine blue assay towards a universal assay protocol for sulfated polysaccharides: Application to fucoidan content in crude extract.
SULF1 Activates the VEGFR2/PI3K/AKT Pathway to Promote the Development of Cervical Cancer.
Corneal Outcomes Following Cataract Surgery Using Ophthalmic Viscosurgical Devices Composed of Chondroitin Sulfate-Hyaluronic Acid: A Systematic Review and Meta-Analysis.
Sex Steroid Metabolism and AcStion in Colon Health and Disease.
The potential role of alfalfa polysaccharides and their sulphated derivatives in the alleviation of obesity.
High throughput LC-MS/MS method for steroid hormone analysis in rat liver and plasma - unraveling methodological challenges.

Sci Rep. 2023 07 29. 13(1): 12313

Sulfated and non-sulfated chondroitin affect the composition and metabolism of human colonic microbiota simulated in an in vitro fermentation system.

Kentaro Inokuma, Daisuke Sasaki, Kaoru Kurata, Megumi Ichikawa, Yuya Otsuka, Akihiko Kondo.

Chondroitin sulfate (CS) is a family of glycosaminoglycans and have a wide range of applications in dietary supplements and pharmaceutical drugs. In this study, we evaluated the effects of several types of CS, differing in their sulfated positions, on the human colonic microbiota and their metabolites. CS (CSA, CSC, and CSE) and non-sulfated chondroitin (CH) were added into an in vitro human colonic microbiota model with fecal samples from 10 healthy individuals. CS addition showed a tendency to increase the relative abundance of Bacteroides, Eubacterium, and Faecalibacterium, and CSC and CSE addition significantly increased the total number of eubacteria in the culture of the Kobe University Human Intestinal Microbiota Model. CSE addition also resulted in a significant increase in short-chain fatty acid (SCFA) levels. Furthermore, addition with CSC and CSE increased the levels of a wide range of metabolites including lysine, ornithine, and Ile-Pro-Pro, which could have beneficial effects on the host. However, significant increases in the total number of eubacteria, relative abundance of Bacteroides, and SCFA levels were also observed after addition with CH, and the trends in the effects of CH addition on metabolite concentrations were identical to those of CSC and CSE addition. These results provide novel insight into the contribution of the colonic microbiota to the beneficial effects of dietary CS.

DOI: https://doi.org/10.1038/s41598-023-38849-5
Br J Clin Pharmacol. 2023 Jul 31.

Evaluation of effects of indoxyl sulfate and parathyroid hormone on CYP3A activity considering the influence of CYP3A5 gene polymorphisms.

Ayako Oda, Yosuke Suzuki, Chisato Yoshijima, Haruki Sato, Ryota Tanaka, Hiroyuki Ono, Ryosuke Tatsuta, Tadasuke Ando, Toshitaka Shin, Hiroki Itoh, Keiko Ohno.

   AIMS: Indoxyl sulfate and parathyroid hormone (PTH), which accumulate in chronic kidney disease (CKD), have been reported to reduce cytochrome P450(CYP)3A activity. Homozygotes of the CYP3A5* 3 allele have reduced CYP3A5 activity compared to carriers of at least one CYP3A5* 1 allele. 4β-hydroxycholesterol (4β-OHC) has been established as an endogenous substrate reflecting CYP3A activity. 4β-OHC is produced through hydroxylation by CYP3A4 and CYP3A5 and by autoxidation of cholesterol, whereas 4α-hydroxycholesterol (4α-OHC) is produced solely by autoxidation of cholesterol. This study focused on CKD patients and evaluated the effects of plasma indoxyl sulfate and intact-PTH concentrations on plasma 4β-OHC concentration, 4β-OHC/total cholesterol ratio, and 4β-OHC - 4α-OHC, with consideration of the influence of CYP3A5 polymorphism.
METHODS: Sixty-three CKD patients were analyzed and divided into CYP3A5 carrier group (N = 26) and non-carrier group (N = 37).
RESULTS: Plasma indoxyl sulfate significantly correlated inversely with 4β-OHC concentration and with 4β-OHC - 4α-OHC in both the CYP3A5* 1 carrier group (r = -0.42, p = 0.034; r = -0.39, p = 0.050, respectively) and the non-carrier group (r = -0.45, p = 0.0054; r = -0.39, p = 0.019, respectively). However, multiple regression analysis did not identify plasma indoxyl sulfate concentration as a significant independent factor associated with any of the CYP3A activity indices. There was no significant correlation between plasma intact-PTH concentration and any of the CYP3A activity indices.
CONCLUSION: The present results suggest that plasma indoxyl sulfate and intact-PTH concentrations do not have clinically significant effects on CYP3A activity in patients with CKD.

Keywords:  4α-hydroxycholesterol; 4β-hydroxycholesterol; chronic kidney disease; cytochrome P450 3A activity; cytochrome P450 3A5 polymorphism; indoxyl sulfate; parathyroid hormone

DOI:  https://doi.org/10.1111/bcp.15866
J Pharm Biomed Anal. 2023 Aug 01. pii: S0731-7085(23)00385-0. [Epub ahead of print]235 115616

A spectroscopic response factor-based toluidine blue assay towards a universal assay protocol for sulfated polysaccharides: Application to fucoidan content in crude extract.

Aya A Abdella, Roland Ulber, Ahmed Zayed.

  Sulfated polysaccharides (SPS) have attracted a lot of interest because of their diverse pharmacological functions. Numerous scientific studies have shown that SPS exhibit better biological activity than those that are not sulfated, such as immunomodulatory, anti-viral, and antioxidant activities. A crucial step to a better understanding of the mechanism of action and health effects is the production of high purity SPS. This calls for the development of selective assay techniques that can identify SPS preferentially without being influenced by other substances or the co-extracted polysaccharides. A universal modified toluidine blue (TB) assay was developed in this study to detect SPS. The assay procedures were conducted using different SPS standards including fucoidans from different biogenic sources, in addition to heparin and dextran sulfate. Spectroscopic response factor was calculated for each SPS which showed very good correlation (R2 = 0.998) with the corresponding sulfation degree. The proposed method was applied for determination of SPS content of crude fucoidan product using five different SPS standards. The method was cross validated by conducting ANOVA test to the obtained % recovery revealing that there is no significant difference between the results obtained by identical reference standard and four nonidentical natural SPS standards. This is the first report of a selective universal assay of SPS that enables the selective determination of SPS using a nonidentical reference standard.

Keywords:  Fucoidans; Reference standards; Response factor; Sulfated polysaccharides; Toluidine blue

DOI:  https://doi.org/10.1016/j.jpba.2023.115616
Curr Cancer Drug Targets. 2023 Aug 04.

SULF1 Activates the VEGFR2/PI3K/AKT Pathway to Promote the Development of Cervical Cancer.

Juan Li, Xihao Wang, Zhilong Li, Minzhen Li, Xuelian Zheng, Danxi Zheng, Yanyun Wang, Mingrong Xi.

   BACKGROUND AND PURPOSE: Sulfatase 1 (SULF1) can regulate the binding of numerous signaling molecules by removing 6-O-sulfate from heparan sulfate proteoglycans (HSPGs) to affect numerous physiological and pathological processes. Our research aimed to investigate the effect of the SULF1-mediated VEGFR2/PI3K/AKT signaling pathway on tumorigenesis and development of cervical cancer (CC).
METHODS: The expression and prognostic values of SULF1 in patients with CC were analyzed through bioinformatics analysis, RT-PCR, immunohistochemistry, and western blot assays. The function and regulatory mechanism of SULF1 in proliferation, migration, and invasion of cervical cancer cells were examined through lentivirus transduction, CCK8, flow cytometry analysis, plate colony formation assay, scratch assay, transwell assay, western blot, VEGFR2 inhibitor (Ki8751), and mouse models.
RESULTS: SULF1 expression was significantly upregulated in CC tissues, which was significantly associated with poor prognosis of patients with CC. In vitro, the upregulation of SULF1 expression in cervical cancer HeLa cells promoted cell proliferation, colony formation, migration, and invasion while inhibiting apoptosis. Conversely, the downregulation of SULF1 expression had the opposite effect. In vivo, the upregulation of SULF1 expression resulted in a significant increase in both tumor growth and angiogenesis, while its downregulation had the opposite effect. Furthermore, western blot detection and cell function rescue assay confirmed that the upregulation of SULF1 in HeLa cells promoted the tumorigenic behaviors of cancer cells by activating the VEGFR2/PI3K/AKT signaling pathway.
CONCLUSION: SULF1 plays an oncogenic role in the tumorigenesis and development of CC, indicating its potential as a novel molecular target for gene-targeted therapy in patients with CC.

Keywords:  Cervical cancer; HeLa cells; Ki8751; SULF1; VEGFR2/PI3K/AKT signaling pathway

DOI:  https://doi.org/10.2174/1568009623666230804161607
Clin Ophthalmol. 2023 ;17 2083-2096

Corneal Outcomes Following Cataract Surgery Using Ophthalmic Viscosurgical Devices Composed of Chondroitin Sulfate-Hyaluronic Acid: A Systematic Review and Meta-Analysis.

Chia-Wen Hsiao, Hang Cheng, Rana Ghafouri, Nicole C Ferko, Brandon D Ayres.

   Background: Ophthalmic viscosurgical devices (OVDs) are commonly used during cataract surgery to protect the corneal endothelium. A systematic literature review and meta-analysis were conducted to assess the clinical evidence of OVDs composed of chondroitin sulfate-hyaluronic acid (CS-HA) versus other OVDs in maintaining endothelial cell density (ECD) and corneal thickness (CT).
Methods: MEDLINE and EMBASE databases were searched from 2000 to 2020. Randomized controlled trials (RCTs, N ≥ 20 per group) comparing an OVD containing CS-HA (ie, VISCOAT®, DuoVisc® or DisCoVisc®) to any other OVD were included. The identified comparators were limited to the OVDs found in the literature, which included those composed of HA-only or hydroxypropyl methylcellulose (HPMC). Outcomes of focus included changes in ECD (baseline to 3 months) and CT (baseline to 24 hours). Meta-analyses were performed using R software, to assess mean differences (MD) in ECD and CT change between CS-HA OVDs and HA-only or HPMC OVDs.
Results: A total of 966 abstracts were screened, and data were extracted from 12 RCTs. Meta-analyses using a random-effects model revealed significantly lower percent (%) decrease in ECD for CS-HA OVDs compared to both HA-only (MD: -4.10%; 95% CI: -5.81 to -2.40; p < 0.0001; 9 studies) and HPMC (MD: -6.47%; 95% CI: -10.41 to -2.52; p = 0.001; 2 studies) products. Similarly, % CT increase was significantly lower with CS-HA than with HA-only OVDs (MD: -3.22%; 95% CI: -6.24% to -0.20%; p = 0.04; 4 studies). However, there were no significant differences when comparing % CT change between CS-HA and HPMC OVDs (MD: 2.65%; 95% CI: -0.43% to 0.95%; p = 0.4; 2 studies).
Conclusion: CS-HA OVDs lead to less postoperative loss of endothelial cells and may better protect corneal endothelium during cataract surgery, relative to other OVDs. Future randomized studies may be needed to solidify these findings.

Keywords:  cataract; corneal thickness; endothelial cell density; endothelial protection; ophthalmic viscosurgical device

DOI:  https://doi.org/10.2147/OPTH.S419863
J Steroid Biochem Mol Biol. 2023 Jul 27. pii: S0960-0760(23)00126-7. [Epub ahead of print] 106371

Sex Steroid Metabolism and AcStion in Colon Health and Disease.

Afnan Banibakhsh, Daljit Sidhu, Sunera Khan, Hope Haime, Paul A Foster.

  The colon is the largest hormonally active tissue in the human body. It has been known for over a hundred years that various hormones and bioactive peptides play important roles in colon function. More recently there is a growing interest in the role the sex steroids, oestrogens and androgens, may play in both normal colon physiology and colon pathophysiology. In this review, we examine the potential role oestrogens and androgens play in the colon. The metabolism and subsequent action of sex steroids in colonic tissue is discussed and how these hormones impact colon motility is investigated. Furthermore, we also determine how oestrogens and androgens influence colorectal cancer incidence and development and highlight potential new therapeutic targets for this malignancy. This review also examines how sex steroids potentially impact the severity and progression of other colon disease, such as diverticulitis, irritable bowel syndrome, and polyp formation.

Keywords:  Androgens; Colon; Colon Cancer; Diverticulitis; Estrogens; Irritable Bowel Syndrome

DOI:  https://doi.org/10.1016/j.jsbmb.2023.106371
Food Funct. 2023 Aug 01.

The potential role of alfalfa polysaccharides and their sulphated derivatives in the alleviation of obesity.

Zhiwei Li, Yawen Wang, Jun Liu, Dan Chen, Guilan Feng, Min Chen, Yuxi Feng, Ran Zhang, Xuebing Yan.

Sulfated alfalfa polysaccharides (SAPs) as derivatives of alfalfa polysaccharides (APs) showed better in vitro antioxidant activity and potential obesity inhibition. The purpose of this study was to investigate the effect and mechanisms of APs and SAPs on obesity alleviation. Different concentrations of APs and SAPs were tested for effects on body conditions, gut flora, antioxidant capacity, and immunological factors. The results showed that APs and SAPs improved the physical conditions of obese mice, including organ weight, body weight, intraperitoneal fat ratio, and lipid levels. APs and SAPs increased the antioxidant capacity of the obese mice, enhanced the activity of SOD and CAT, and decreased the activity of MDA in the serum, liver, and colon. APs and SAPs upregulated the mRNA expression of IL-4 and IL-10 and downregulated the mRNA expression of NF-κB, IFN-γ, TNF-α, and IL-6 in the liver and colon. Meanwhile, APs and SAPs improved lipid absorption in the jejunum, upregulated LXR and GLP-2, and down-regulated the mRNA expression of NPC1L1. APs and SAPs also contributed to restoring short-chain fatty acid levels in the colon. APs and SAPs improved the structure of the intestinal flora, promoted the proliferation of bacteria associated with short-chain fatty acid metabolism, and inhibited the proliferation of pathogenic bacteria. At the same concentration, the effect of SAPs on the antioxidant capacity was stronger than that of APs. In the AP group, high concentrations of APs showed the best anti-inflammatory effect, while in the SAP group, medium concentrations of SAPs showed the best inhibition of inflammation. Our results suggest that APs and SAPs alleviate obesity symptoms by relieving inflammation, improving the antioxidant capacity, and regulating intestinal flora and therefore could be used as potential probiotic products to alleviate obesity.

DOI: https://doi.org/10.1039/d3fo01390a
Talanta. 2023 Jul 24. pii: S0039-9140(23)00732-4. [Epub ahead of print]266(Pt 1): 124981

High throughput LC-MS/MS method for steroid hormone analysis in rat liver and plasma - unraveling methodological challenges.

Sara Evangelista, Paraskevi Vazakidou, Jacco Koekkoek, Manuel T Heinzelmann, Walter Lichtensteiger, Margret Schlumpf, Jesus A F Tresguerres, Beatriz Linillos-Pradillo, Majorie B M van Duursen, Marja H Lamoree, Pim E G Leonards.

  Comprehensive reference data for steroid hormones are lacking in rat models, particularly for early developmental stages and unconventional matrices as the liver. Therefore, we developed and validated an enzymatic, solid-phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify a panel of 23 steroid hormones in liver and plasma from adult and neonatal rats. Our approach tackles methodological challenges, focusing on undesired byproducts associated with specific enzymatic treatment, and enables a thorough assessment of potential interferences in complex matrices by utilizing unstripped plasma and liver. We propose an optimized enzymatic hydrolysis protocol using a recombinant β-glucuronidase/sulfatase mix (BGS mix) to efficiently deconjugate steroid phase II conjugates. The streamlined sample preparation and high-throughput solid phase extraction in a 96-well plate significantly accelerate sample processing for complex matrices and alarge number of samples. We were able to achieve the necessary sensitivity for accurately measuring the target analytes, particularly estrogens, in small sample sizes of 5-20 mg of liver tissue and 100 μL of plasma. Through the analysis of liver and plasma samples from adult and neonatal rats, including both sexes, our study showed a novel set of steroid hormone reference intervals. This study provides a reliable diagnostic tool for the quantification of steroids in rat models and gives insight in liver and plasma-related steroid hormone dynamics at early developmental stages. In addition, the method covers several pathway intermediates and extend the list of steroid hormones to be investigated.

Keywords:  Adult and neonatal rats; Liquid chromatography-tandem mass spectrometry; Recombinant enzymes; Steroid hormones

DOI:  https://doi.org/10.1016/j.talanta.2023.124981