bims-supasi 2023-01-01 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2023‒01‒01
fourteen papers selected by
Jonathan Wolf Mueller
University of Birmingham

Altered sulfation status of FAM20C-dependent chondroitin sulfate is associated with osteosclerotic bone dysplasia.
Sex differences in hippocampal structural plasticity and glycosaminoglycan disaccharide levels after neonatal handling.
Chondroitin sulfate and L-Cysteine conjugate modified cationic nanostructured lipid carriers: Pre-corneal retention, permeability, and related studies for dry eye treatment.
Serum sulfate level and Slc13a1 mRNA expression remain unaltered in a mouse model of moderate vitamin D deficiency.
Adrenal steroids and resistance to hormonal blockade of prostate and breast cancer.
A potential antibody repertoire diversification mechanism through tyrosine sulfation for biotherapeutics engineering and production.
The Phytochemical Curcumin Inhibits Steroid Sulfatase Activity in Rat Liver Tissue and NIH-3T3 Mouse Fibroblast Cells.
Evaluation of androgen-dependent skin findings of polycystic ovary syndrome (PCOS).
Amelioration of atherosclerosis in ox-LDL induced HUVEC by sulfated polysaccharides from Gelidium crinale with antihypertensive activity.
Enzymatic Process for the Carrageenolytic Bioconversion of Sulfated Polygalactans into β-Neocarrabiose and 3,6-Anhydro-d-galactose.
Changes in hormones, Leukocyte Telomere Length (LTL), and p16INK4a expression in SM-exposed individuals in favor of the cellular senescence.
Novel Magnetic-Bead-Assisted Sequential Extraction Method for Liquid Chromatography-Mass Spectrometry (MS)/MS of Components with Diverse Properties: Gastrin Determination as a Case Study.
N-desulfated and reacetylated modification of heparin modulates macrophage polarization.
Comparison of Commercial Low Molecular Weight Heparin and Homemade Anti-Xa Calibrators to a Commercial Specific Anti-Xa Calibrator for Plasma Rivaroxaban Quantification by Anti-Xa Oral Anticoagulant Plasma Concentration Chromogenic Assay.

Nat Commun. 2022 Dec 26. 13(1): 7952

Altered sulfation status of FAM20C-dependent chondroitin sulfate is associated with osteosclerotic bone dysplasia.

Toshiyasu Koike, Tadahisa Mikami, Jun-Ichi Tamura, Hiroshi Kitagawa.

Raine syndrome, a lethal osteosclerotic bone dysplasia in humans, is caused by loss-of-function mutations in FAM20C; however, Fam20c deficiency in mice does not recapitulate the human disorder, so the underlying pathoetiological mechanisms remain poorly understood. Here we show that FAM20C, in addition to the reported casein kinase activity, also fine-tunes the biosynthesis of chondroitin sulfate (CS) chains to impact bone homeostasis. Specifically, FAM20C with Raine-originated mutations loses the ability to interact with chondroitin 4-O-sulfotransferase-1, and is associated with reduced 4-sulfation/6-sulfation (4S/6S) ratio of CS chains and upregulated biomineralization in human osteosarcoma cells. By contrast, overexpressing chondroitin 6-O-sulfotransferase-1 reduces CS 4S/6S ratio, and induces osteoblast differentiation in vitro and higher bone mineral density in transgenic mice. Meanwhile, a potential xylose kinase activity of FAM20C does not impact CS 4S/6S ratio, and is not associated with Raine syndrome mutations. Our results thus implicate CS 4S/6S ratio imbalances caused by FAM20C mutations as a contributor of Raine syndrome etiology.

DOI: https://doi.org/10.1038/s41467-022-35687-3
Exp Neurol. 2022 Dec 24. pii: S0014-4886(22)00338-7. [Epub ahead of print]361 114313

Sex differences in hippocampal structural plasticity and glycosaminoglycan disaccharide levels after neonatal handling.

Joel G Hashimoto, Mo L Singer, Calla M Goeke, Fuming Zhang, Yuefan Song, Ke Xia, Robert J Linhardt, Marina Guizzetti.

  In this study we investigated the effects of a neonatal handling protocol that mimics the handling of sham control pups in protocols of neonatal exposure to brain insults on dendritic arborization and glycosaminoglycan (GAG) levels in the developing brain. GAGs are long, unbranched polysaccharides, consisting of repeating disaccharide units that can be modified by sulfation at specific sites and are involved in modulating neuronal plasticity during brain development. In this study, male and female Sprague-Dawley rats underwent neonatal handling daily between post-natal day (PD)4 and PD9, with brains analyzed on PD9. Neuronal morphology and morphometric analysis of the apical and basal dendritic trees of CA1 hippocampal pyramidal neurons were carried out by Golgi-Cox staining followed by neuron tracing and analysis with the software Neurolucida. Chondroitin sulfate (CS)-, Hyaluronic Acid (HA)-, and Heparan Sulfate (HS)-GAG disaccharide levels were quantified in the hippocampus by Liquid Chromatography/Mass Spectrometry analyses. We found sex by neonatal handling interactions on several parameters of CA1 pyramidal neuron morphology and in the levels of HS-GAGs, with females, but not males, showing an increase in both dendritic arborization and HS-GAG levels. We also observed increased expression of glucocorticoid receptor gene Nr3c1 in the hippocampus of both males and females following neonatal handling suggesting that both sexes experienced a similar stress during the handling procedure. This is the first study to show sex differences in two parameters of brain plasticity, CA1 neuron morphology and HS-GAG levels, following handling stress in neonatal rats.

Keywords:  Dendritic arborization; Glycosaminoglycans (GAGs); Neonatal handling; Sex differences

DOI:  https://doi.org/10.1016/j.expneurol.2022.114313
Int J Biol Macromol. 2022 Dec 26. pii: S0141-8130(22)03150-6. [Epub ahead of print]

Chondroitin sulfate and L-Cysteine conjugate modified cationic nanostructured lipid carriers: Pre-corneal retention, permeability, and related studies for dry eye treatment.

Renfang Zhu, Wenyue Chen, Donghao Gu, Tianyi Wang, Jiayang Li, Hao Pan.

  In this study, a novel bioadhesive material, a conjugate of chondroitin sulfate and L-cysteine (CS-Cys), was synthesized and modified on the surface of the cationic nanostructured lipid carriers loaded dexamethasone to prepare a novel nano-lipid ocular delivery system (Dex-CS-Cys-cNLC). Through the permeation and retention studies of isolated cornea, it was demonstrated that Dex-CS-Cys-cNLC has better corneal permeation and retention ability and can better overcome the barrier effect of the ocular surface. In addition, the fluorescent probe (RhB) was used to replace the drug, and fluorescence imaging was used to investigate the ocular surface retention ability of the formulation, and the results showed that CS-Cys-cNLC has stronger retention ability and can effectively prolong the time of drug action in the ocular surface. Dex-CS-Cys-cNLC was not irritating to rabbit eye tissues and was a safe delivery system. The results of rabbit dry eye pharmacodynamic experiments also showed that Dex-CS-Cys-cNLC could effectively alleviate dry eye symptoms in rabbits, effectively repair corneal damage, and improve the stability of tear film. All these experimental results suggest that Dex-CS-Cys-cNLC is a promising drug delivery carrier for the treatment of anterior segment of the eye disease.

Keywords:  Chondroitin sulfate; Dry eye disease; Nanostructured lipid carriers

DOI:  https://doi.org/10.1016/j.ijbiomac.2022.12.238
Mol Cell Biochem. 2022 Dec 25.

Serum sulfate level and Slc13a1 mRNA expression remain unaltered in a mouse model of moderate vitamin D deficiency.

Ranita J Atcheson, Thomas H J Burne, Paul A Dawson.

  Sulfate is essential for healthy foetal growth and neurodevelopment. The SLC13A1 sulfate transporter is primarily expressed in the kidney where it mediates sulfate reabsorption and maintains circulating sulfate levels. To meet foetal demands, maternal sulfate levels increase by twofold in pregnancy via upregulated SLC13A1 expression. Previous studies found hyposulfataemia and reduced renal Slc13a1 mRNA expression in rodent models with either severe vitamin D deficiency or perturbed vitamin D signalling. Here we investigated a mouse model of moderate vitamin D deficiency. However, serum sulfate level and renal Slc13a1 mRNA expression was not decreased by a moderate reduction in circulating vitamin D level. We confirmed that the mouse Slc13a1 5'-flanking region was upregulated by 1,25(OH)2D3 using luciferase assays in a cultured renal OK cell line. These results support the presence of a functional VDRE in the mouse Slc13a1 but suggests that moderate vitamin D deficiency does not impact on sulfate homeostasis. As sulfate biology is highly conserved between rodents and humans, we proposed that human SLC13A1 would be under similar transcriptional regulation by 1,25(OH)2D3. Using an online prediction tool we identified a putative VDRE in the SLC13A1 5'-flanking region but unlike the mouse Slc13a1 sequence, the human sequence did not confer a significant response to 1,25(OH)2D3 in vitro. Overall, this study suggests that moderate vitamin D deficiency may not alter sulfate homeostasis. This needs to be confirmed in humans, particularly during pregnancy when vitamin D and sulfate levels need to be maintained at high levels for healthy maternal and child outcomes.

Keywords:  Gene expression; Mouse model; Sulfate; Transcriptional regulation; Vitamin D

DOI:  https://doi.org/10.1007/s11010-022-04634-7
Endocrinology. 2022 Dec 29. pii: bqac218. [Epub ahead of print]

Adrenal steroids and resistance to hormonal blockade of prostate and breast cancer.

Patrick Michael, Gustavo Roversi, Kristy Brown, Nima Sharifi.

  Prostate cancer and breast cancer are sex-steroid-dependent diseases that are driven in major part by gonadal sex steroids. Testosterone is converted to 5α-dihydrotestosterone, both of which stimulate the androgen receptor (AR) and prostate cancer progression. Estradiol is the major stimulus for estrogen receptor (ER)-α and proliferation of ERα-expressing breast cancer. However, the human adrenal provides an alternative source for sex steroids. A number of different androgens are produced by the adrenals, the most abundant of which is dehydroepiandrosterone (DHEA) and DHEA-sulfate. These precursor steroids are subject to metabolism by peripherally expressed enzymes that are responsible for the synthesis of potent androgens and estrogens. In the case of prostate cancer, the regulation of one of these enzymatic steps occurs at least in part by way of a germline-encoded missense in 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which regulates potent androgen biosynthesis and clinical outcomes in men with advanced prostate cancer treated with gonadal testosterone deprivation. The sex steroids that drive prostate cancer and breast cancer require a common set of enzymes for their generation. However, the pathways diverge once 3-keto, Δ4-androgens are generated and these steroids are either turned into potent androgens by steroid-5α-reductase, or into estrogens by aromatase. Alternative steroid receptors have also emerged as disease- and treatment-resistance modifiers, including a role for AR in breast cancer and glucocorticoid receptor (GR) in both breast and prostate cancer. In this review, we integrate the commonalities of adrenal steroid physiology that regulate both prostate and breast cancer while recognizing the clear distinctions between these diseases.

Keywords:  Androgens; adrenals; breast cancer; estrogens; hormones; metabolism; prostate cancer; steroids

DOI:  https://doi.org/10.1210/endocr/bqac218
Front Immunol. 2022 ;13 1072702

A potential antibody repertoire diversification mechanism through tyrosine sulfation for biotherapeutics engineering and production.

Xiaotian Zhong, Aaron M D'Antona.

  The diversity of three hypervariable loops in antibody heavy chain and light chain, termed the complementarity-determining regions (CDRs), defines antibody's binding affinity and specificity owing to the direct contact between the CDRs and antigens. These CDR regions typically contain tyrosine (Tyr) residues that are known to engage in both nonpolar and pi stacking interaction with antigens through their complementary aromatic ring side chains. Nearly two decades ago, sulfotyrosine residue (sTyr), a negatively charged Tyr formed by Golgi-localized membrane-bound tyrosylprotein sulfotransferases during protein trafficking, were also found in the CDR regions and shown to play an important role in modulating antibody-antigen interaction. This breakthrough finding demonstrated that antibody repertoire could be further diversified through post-translational modifications, in addition to the conventional genetic recombination. This review article summarizes the current advances in the understanding of the Tyr-sulfation modification mechanism and its application in potentiating protein-protein interaction for antibody engineering and production. Challenges and opportunities are also discussed.

Keywords:  antibody repertoire diversification; antigen-binding affinity; biotherapeutic engineering and production; complementarity determination region (CDR); tyrosine sulfation

DOI:  https://doi.org/10.3389/fimmu.2022.1072702
Steroids. 2022 Dec 26. pii: S0039-128X(22)00202-1. [Epub ahead of print] 109163

The Phytochemical Curcumin Inhibits Steroid Sulfatase Activity in Rat Liver Tissue and NIH-3T3 Mouse Fibroblast Cells.

Barathi Balasubramonian, Kyle W Selcer.

  Curcumin is a phytochemical derived from the spice turmeric that is reported to have therapeutic effects. We are studying the enzyme steroid sulfatase (STS), which removes the sulfate group from inactive steroid hormones in peripheral tissues and we were interested in the effect of curcumin on STS activity due to its structural composition (polyphenolic). We sought to determine if curcumin affects STS activity in two model systems, rat liver and NIH-3T3 mouse fibroblast cells. STS assays were performed on tissue extracts of rat liver, and on NIH-3T3 microsomes and cells, with and without curcumin. Male and female rat liver extracts contained substantial amounts of STS activity, with males averaging higher (4-11%) levels. Estradiol inhibited STS activity in livers of both sexes at 20 and 10µM. Curcumin acted as a competitive inhibitor of STS activity in rat liver extracts, with a Ki of 19.8µM in males and 9.3µM in females. Curcumin also inhibited STS activity in NIH-3T3 microsomes at both 20µM and 10µM, and in whole NIH-3T3 cells at 20µM. These data are the first to demonstrate STS inhibition by curcumin. Inhibition of STS results in lower active steroid hormone (estrogens and androgens) levels in tissues, possibly altering modulation of immune responses by these steroids.

Keywords:  Enzyme inhibition; curcumin; estrogens; mouse fibroblast; rat liver; steroid sulfatase

DOI:  https://doi.org/10.1016/j.steroids.2022.109163
Gynecol Endocrinol. 2022 Dec 29. 1-5

Evaluation of androgen-dependent skin findings of polycystic ovary syndrome (PCOS).

Gokhan Artar, Betul Tas, Gokce Turan, Hasan Huseyin Uckan.

  AIM: The purpose of the study was to investigate the biochemical and metabolic abnormalities related to the cutaneous characteristics of PCOS.MATERIAL–METHODS: Patients diagnosed with PCOS were included in the study. Demographic data and accompanying androgen-dependent skin findings (acne, seborrhea, androgenic alopecia, acanthosis nigricans, skin tag, and hirsutism) were recorded. The free testosterone, total testosterone, dehydroepiandrosterone sulfate, androstenedione,17-Hidroksi progesterone, sex hormone binding globulin, prolactin, fasting glucose, fasting insulin, HbA1C, HDL, and triglycerides, follicle-stimulating hormone, luteinized hormone, free androgen index, and HOMA-IR levels of the patients were measured. The hormonal values of the patients with PCOS with and without skin findings were compared.
RESULTS: The HOMA-IR values of the acanthosis nigricans (+) PCOS group were significantly higher than the acanthosis nigricans (-) PCOS group (p < .001). The DHEA-SO4, FAI, and FI values of patients with hirsutism (HR) (+) PCOS were found to be statistically higher than patients with HR (-) PCOS (p = .006, p = .015, p = .004).
CONCLUSION: PCOS is among the most common endocrine disorders of women of reproductive age and was associated with some hormonal, metabolic, and skin findings. Certain androgenic and metabolic variables developing in PCOS might correlate with cutaneous symptoms.

Keywords:  Acne; hirsutism; polycystic ovary syndrome; seborrhea

DOI:  https://doi.org/10.1080/09513590.2022.2162496
Int J Biol Macromol. 2022 Dec 25. pii: S0141-8130(22)03156-7. [Epub ahead of print]

Amelioration of atherosclerosis in ox-LDL induced HUVEC by sulfated polysaccharides from Gelidium crinale with antihypertensive activity.

Haiyan Zheng, Yu Pei, Chunxia Zhou, Pengzhi Hong, Zhong-Ji Qian.

  Red algal polysaccharide is a good potential medical resource. Different red algal polysaccharides have different structural characteristics and rich biological activities. Previous studies have identified some structural information of sulfated polysaccharide (GNP, 25.8 kDa) from red algae, Gelidium crinale and found that GNP has excellent anti-inflammatory, antioxidant and anti-tumor activities. On this basis, this study investigated the effect of GNP on atherosclerosis, which is closely related to antioxidant and anti-inflammatory mechanisms and usually coexists and interacts with hypertension. This study investigated the inhibitory activity of GNP on angiotensin-converting enzyme (ACE) and its mechanism on oxidized low-density lipoprotein (ox-LDL)-induced HUVEC atherosclerosis. The results showed that GNP inhibits the up-regulation of cell adhesion molecules and oxidized low-density lipoprotein receptor-1 (LOX-1). GNP can regulate mitogen-activated protein kinases (MAPK), nuclear factor kappa B (NF-κB) and PI3K/AKT signal pathways, inhibit apoptosis, invasion and migration. Meanwhile, GNP (IC50 = 269.2 μg/mL) antagonizes ACE by competitive binding mode, and it can reduce systolic blood pressure (SBP) of spontaneously hypertensive rats (SHR). It provides a theoretical basis for GNP as a potential substance for the prevention and treatment of atherosclerosis.

Keywords:  Atherosclerosis; Gelidium crinale; Sulfated polysaccharide

DOI:  https://doi.org/10.1016/j.ijbiomac.2022.12.245
J Agric Food Chem. 2022 Dec 29.

Enzymatic Process for the Carrageenolytic Bioconversion of Sulfated Polygalactans into β-Neocarrabiose and 3,6-Anhydro-d-galactose.

Duleepa Pathiraja, Junghwan Cho, Peter Stougaard, In-Geol Choi.

  Oligosaccharides and anhydro-sugars derived from carrageenan have great potential as functional foods and drugs showing various bioactivities, including antioxidant, anti-inflammatory, antiviral, antitumor, and cytotoxic activities. Although preparation of sulfated carrageenan oligosaccharides by chemical and enzymatic processes has been widely reported, preparation of nonsulfated β-neocarrabiose (β-NC2) and the rare sugar 3,6-anhydro-d-galactose (d-AHG) was not reported in the literature. Based on the carrageenan catabolic pathway in marine heterotrophic bacteria, an enzymatic process was designed and constructed with recombinant κ-carrageenase, GH127/GH129 α-1,3 anhydrogalactosidase, and cell-free extract from marine carrageenolytic bacteria Colwellia echini A3T. The process consisted of three successive steps, namely, (i) depolymerization, (ii) desulfation, and (iii) monomerization, by which carrageenan oligosaccharides, β-NC2, and d-AHG were obtained from κ-carrageenan. Unlike the chemical process, enzymatic hydrolysis yields oligosaccharides with the desired degree of polymerization facilitates specific removal of sulfated groups, free of toxic byproducts, and avoids chemical modifications. The final optimized enzymatic process produced 0.52 g of β-NC2 and 0.24 g of d-AHG from 1 g of κ-carrageenan. The carrageenolytic process designed for the enzymatic hydrolysis of κ-carrageenan can be scaled up for the mass production of bioactive carrageeno-oligosaccharides.

Keywords:  GH127; GH129; S1_19 family sulfatase; carrageenan catabolism; carrageeno-oligosaccharides; d-AHG; neocarrabiose; sulfated polygalactans; β-neocarrabiose

DOI:  https://doi.org/10.1021/acs.jafc.2c06972
Drug Chem Toxicol. 2022 Dec 27. 1-7

Changes in hormones, Leukocyte Telomere Length (LTL), and p16INK4a expression in SM-exposed individuals in favor of the cellular senescence.

Susan K Ardestani, Tahereh Jamali, Ali Taravati, Hossein Behboudi, Mohamad-Reza Vaez-Mahdavi, Elham Faghihzadeh, Tooba Ghazanfari.

  Sulfur mustard (SM) is a chemical warfare agent with well-known severe toxic effects and may cause long-term debilitating injuries. We aimed to evaluate aging and longevity in Iranian SM-exposed survivors using some endocrine and molecular biomarkers for the first time. Dehydroepiandrosterone (DHEA), prolactin (PRL), cortisol, testosterone, and luteinizing hormone (LH) were measured in 289 male SM-veterans and 66 age-matched males using the ELISA method. Leukocyte Telomere Length (LTL) measurement and p16INK4a expression were measured in the peripheral blood leukocytes of 55 males who were exposed to SM. We found a significantly lower serum DHEAS level and higher serum PRL level in SM-exposed groups (without any related to the severity of lung injuries) compared to healthy controls, but no significant difference in serum levels of cortisol, testosterone, and LH. The molar ratio of DHEAS/cortisol was significantly higher in controls compared to the SM-exposed individuals especially those with severe lung damage. Some biological parameters of allostatic load score such as DHEAS and DHEAS/cortisol ratio significantly decreased long-term after the SM exposure. Additionally, we found that LTL was shorter in SM-exposed veterans rather than unexposed controls while p16INK4a gene expression significantly increased in these groups. It seems that DHEAS, DHEAS/cortisol ratio, LTL, and p16INK4a gene expression have changed significantly in favor of cellular senescence in SM-exposed patients. Therefore, it seems that SM exposure increases biological age compared to chronological age in SM-exposed survivors.

Keywords:  DHEA; P16; Sulfur mustard (SM); gene expression; telomere

DOI:  https://doi.org/10.1080/01480545.2022.2150205
Anal Chem. 2022 Dec 29.

Novel Magnetic-Bead-Assisted Sequential Extraction Method for Liquid Chromatography-Mass Spectrometry (MS)/MS of Components with Diverse Properties: Gastrin Determination as a Case Study.

Xiaoli Ma, Yutong Zou, DanChen Wang, Danni Mu, Jian Zhong, Fengying Gong, Huijuan Zhu, Ailing Song, Songlin Yu, Ling Qiu.

Sample preparation is the rate-limiting step in liquid chromatography-mass spectrometry (LC-MS)/MS-based clinical analysis when target analytes possess significantly different properties. Repeated solid-phase extraction (SPE) processes are typically required, resulting in low throughput and excessive consumption of labor, materials, and samples. In this study, we developed and validated a feasible and productive method to enrich target analytes with different properties during a single operation, while sufficiently removing matrix interferences to meet LC-MS/MS requirements. Gastrin determination was selected as the subject of this study. An automated magnetic-bead-assisted sequential extraction (MBASE) workflow was developed to simultaneously isolate nonsulfated gastrin-17 (G17ns), sulfated gastrin-17 (G17s), nonsulfated gastrin-34 (G34ns), and sulfated gastrin-34 (G34s) from human serum. It performs two different ion-exchange-based magnetic-bead extraction steps on one sample aliquot to produce one combined extract for LC-MS/MS analysis. When compared with the traditional SPE process, the MBASE workflow saves over 75% time and labor expenses as well as over 90% material cost, while providing even higher extraction efficiency. The MBASE LC-MS/MS method was validated as accurate and robust. Clinical sample test results demonstrated that the conventional chemiluminescence immunoassay method significantly under-estimated total gastrins in human serum, and the MBASE LC-MS/MS method could serve as an ideal tool to provide a comprehensive and accurate gastrin profile.

DOI: https://doi.org/10.1021/acs.analchem.2c02970
Int J Biol Macromol. 2022 Dec 21. pii: S0141-8130(22)03124-5. [Epub ahead of print]

N-desulfated and reacetylated modification of heparin modulates macrophage polarization.

Min Zhu, Xiaotao Wu, Jun Sun, Zhou Zhou, Mingzhu Kang, Yiwei Hu, Liping Teng.

  Heparin as a widely used anticoagulant drug has potent anti-inflammatory effects, which have been rarely reported to be involved in macrophage polarization. Furthermore, the effects of structural modifications of heparin on the plasticity of macrophage functions have not been clearly understood. In this study, the N-desulfated reacetylated derivative of heparin (NDeSAcH) was prepared and its immunoregulatory effects of macrophage polarization were evaluated. The findings indicated that NDeSAcH could effectively promote the release of more nitric oxide (NO), interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in RAW264.7 cells than heparin. Moreover, the production of NO, IL-6 and TNF-α was significantly inhibited by NDeSAcH in LPS-induced RAW264.7 cells, while the secretion of transforming growth factor-β (TGF-β) was suppressed in M2 macrophages. The N-desulfated and reacetylated group of heparin was proved to have two-side adjusting effects on the polarization of macrophages. This study suggested that NDeSAcH might be a promising candidate for modulating macrophage polarization and treating inflammation-related diseases.

Keywords:  Acetylation; Heparin; Macrophage; Polarization; Polysaccharide

DOI:  https://doi.org/10.1016/j.ijbiomac.2022.12.213
Lab Med. 2022 Dec 27. pii: lmac137. [Epub ahead of print]

Comparison of Commercial Low Molecular Weight Heparin and Homemade Anti-Xa Calibrators to a Commercial Specific Anti-Xa Calibrator for Plasma Rivaroxaban Quantification by Anti-Xa Oral Anticoagulant Plasma Concentration Chromogenic Assay.

Bita Divsalar, Tahereh Kalantari, Soheila Mohebbi, Ardeshir Bahmanimehr, Amin Shahsavani, Afshin Borhani-Haghighi.

  OBJECTIVE: The main concern about measuring the concentration of rivaroxaban by anti-Xa assay in some laboratories is the lack of a commercial specific calibrator in emergencies. Therefore, this study aimed at providing a homemade anti-Xa calibrator and commercial low molecular weight heparin (LMWH) anti-Xa calibrator.METHODS: The anti-Xa plasma concentration of rivaroxaban was measured in 70 patients using a commercial specific anti-Xa calibrator, a commercial LMWH anti-Xa calibrator, and a homemade anti-Xa calibrator.
RESULTS: We demonstrated a significant correlation and agreement (P < .001) between LMWH-calibrated anti-Xa and the commercial specific calibrator. A significant correlation (P < .001) was found between homemade calibrated anti-Xa made by normal pooled plasma and that calibrated with a commercial specific drug. The nonspecific homemade and LMWH calibrators had excellent agreement (P < .001) and can be used interchangeably.
CONCLUSION: Our data showed that for estimating rivaroxaban concentrations, the LMWH calibrator could be used as an alternative calibrator in the anti-Xa assay.

Keywords:  Anti-Xa; NPP; homemade calibrator made by spiked normal pooled plasma; laboratory; low molecular weight heparin; rivaroxaban

DOI:  https://doi.org/10.1093/labmed/lmac137