bims-supasi 2023-10-15 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2023–10–15
fiveteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Molecular mechanism of decision-making in glycosaminoglycan biosynthesis.
Human cytosolic steroid sulfotransferases: Versatile and rapid activity assays.
Comparative evaluation of cytotoxic and anti-metastatic function of microbial chondroitin sulfate and animal-originated commercial chondroitin sulfate in cancer cells.
Aromatase and steroid sulfatase from human placenta.
Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A.
Exogenous recombinant N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) inhibits progression of B16F10 cutaneous melanomas and modulates cell signaling.
Biosynthesized silver nanoparticles-capped chondroitin sulfate nanogel targeting microbial infections and biofilms for biomedical applications.
Multicomponent analysis of dietary supplements containing glucosamine and chondroitin: comparative low- and high-field NMR spectroscopic study.
Traits linked to natural variation of sulfur content in A. thaliana leaf.
Fabrication and optimization of multilayered composite scaffold made of sulfated alginate-based nanofiber/decellularized Wharton's jelly ECM for tympanic membrane tissue engineering.
A combination of 5/6-nephrectomy and unilateral ureteral obstruction model accelerates progression of remote organ fibrosis in chronic kidney disease.
p-Cresol Sulfate Is a Sensitive Urinary Marker of Fecal Microbiota Transplantation and Antibiotics Treatments in Human Patients and Mouse Models.
Brief history of the alcohol biomarkers CDT, EtG, EtS, 5-HTOL, and PEth.
The Acute Effect of Hydroxychloroquine Sulfate on Hunger, the Plasma Concentration of Orexigenic Peptides and Hedonic Food Intake: A Pilot Study.
The endothelial glycocalyx-All the same? No, it is not.

Nat Commun. 2023 Oct 13. 14(1): 6425

Molecular mechanism of decision-making in glycosaminoglycan biosynthesis.

Douglas Sammon, Anja Krueger, Marta Busse-Wicher, Rhodri Marc Morgan, Stuart M Haslam, Benjamin Schumann, David C Briggs, Erhard Hohenester.

Two major glycosaminoglycan types, heparan sulfate (HS) and chondroitin sulfate (CS), control many aspects of development and physiology in a type-specific manner. HS and CS are attached to core proteins via a common linker tetrasaccharide, but differ in their polymer backbones. How core proteins are specifically modified with HS or CS has been an enduring mystery. By reconstituting glycosaminoglycan biosynthesis in vitro, we establish that the CS-initiating N-acetylgalactosaminyltransferase CSGALNACT2 modifies all glycopeptide substrates equally, whereas the HS-initiating N-acetylglucosaminyltransferase EXTL3 is selective. Structure-function analysis reveals that acidic residues in the glycopeptide substrate and a basic exosite in EXTL3 are critical for specifying HS biosynthesis. Linker phosphorylation by the xylose kinase FAM20B accelerates linker synthesis and initiation of both HS and CS, but has no effect on the subsequent polymerisation of the backbone. Our results demonstrate that modification with CS occurs by default and must be overridden by EXTL3 to produce HS.

DOI: https://doi.org/10.1038/s41467-023-42236-z
Methods Enzymol. 2023 ;pii: S0076-6879(23)00132-5. [Epub ahead of print]689 332-352

Human cytosolic steroid sulfotransferases: Versatile and rapid activity assays.

Charles N Falany, Patrick L Garcia, M Iqbal Hossain, Robert C A M van Waardenburg.

  Conjugation of steroids and sterol compounds with a sulfonate group is a major pathway in the regulation of their activity, synthesis and excretion. Three human cytosolic sulfotransferases are highly involved in the sulfonation of sterol compounds. SULT1E1 has a low nM affinity for estrogen sulfonation and also conjugates non-aromatic steroids with a significantly lower affinity. SULT2A1 is responsible for the high levels of fetal and adult dehydroepiandrosterone (DHEA) sulfate synthesis in the adrenal gland as well as many 3α and 3ß-hydroxysteroids and bile acids. SULT2B1b is responsible for the majority of cholesterol sulfation in tissues as well as conjugating 3ß-hydroxysteroids. Although there are multiple methods for assaying cytosolic SULT activity, two relatively simple, rapid and versatile assays for steroid sulfonation are described. The first method utilizes radiolabeled substrates and organic solvent extraction to isolate the radiolabeled product from the aqueous phase. The second assay utilizes 35S-3'-phosphoadenosine 5'-phosphosulfate (PAPS) to generate 35S-conjugated products that are resolved by thin layer chromatography. Both assays useful in situations requiring measurement of SULT activity in a timely manner.

Keywords:  3′,5’-diphosphoadenosine (PAP); 3′-phosphoadenosine 5′-phosphosulfate (PAPS); dehydroepiandrosterone (DHEA); phase 2 conjugation; sulfonation; sulfotransferase (SULT); ß-Estradiol (ß-E2)

DOI:  https://doi.org/10.1016/bs.mie.2023.04.008
Cell Mol Biol (Noisy-le-grand). 2023 Sep 30. 69(9): 8-14

Comparative evaluation of cytotoxic and anti-metastatic function of microbial chondroitin sulfate and animal-originated commercial chondroitin sulfate in cancer cells.

Tuba Unver, Selcen Celik-Uzuner, Ayse Sebnem Erenler.

Cancer has the second-highest mortality rate worldwide after cardiovascular disease. In addition, breast and cervical cancer are two of the leading causes of cancer-related deaths among women. The tumor microenvironment, which consists of fibroblasts, immune cells, cells that form blood vessels, and proteins, is a therapeutic target for cancer therapy. As part of the cellular microenvironment, glycosaminoglycan chondroitin sulfate is associated with various aspects of tumor progression and metastasis depending on the sulfate pattern of chondroitin sulfate. This study evaluated the roles of Microbial Chondroitin Sulfate (CS) and Commercial CS in tumor growth and metastasis comparatively using MDA-MB-231 metastatic breast cancer cells, HeLa cervical cancer cells, and normal fibroblasts. In addition, the role of CS types in wound healing was also assessed comparatively. Microbial CS was more cytotoxic in MDA-MB-231 cells than HeLa compared to Commercial CS. Although both CS reduced cell viability in normal cells, the selective index of Microbial CS in MDA-MB-213 cells was higher than its commercial counterpart. In addition, the role of CS types in wound healing was also assessed comparatively. Both types of CS decreased the cell migration in MDA-MB-231 cancer cells, but HeLa cells were more sensitive to Microbial CS than Commercial CS to heal the wound. The wound healing of NIH3T3 cells after Microbial CS was similarly high to the healing after Commercial CS. This preliminary study shows that microbial CS produced by biotechnological methods from a recombinant source created by our team can be an effective therapeutic agent in various types of cancer.

DOI: https://doi.org/10.14715/cmb/2023.69.9.2
Methods Enzymol. 2023 ;pii: S0076-6879(23)00163-5. [Epub ahead of print]689 67-86

Aromatase and steroid sulfatase from human placenta.

Debashis Ghosh.

  Cytochrome P450 aromatase (AROM) and steroid (estrone (E1)/dehydroepiandrosterone (DHEA)) sulfatase (STS) are the two key enzymes responsible for the biosynthesis of estrogens in human, and maintenance of the critical balance between androgens and estrogens. Human AROM, an integral membrane protein of the endoplasmic reticulum, is a member of the Fe-heme containing cytochrome P450 superfamily having a cysteine thiolate as the fifth Fe-coordinating ligand. It is the only enzyme known to catalyze the conversion of androgens with non-aromatic A-rings to estrogens characterized by the aromatic A-ring. Human STS, also an integral membrane protein of the endoplasmic reticulum, is a Ca2+-dependent enzyme that catalyzes the hydrolysis of sulfate esters of E1 and DHEA to yield the respective unconjugated steroids, the precursors of the most potent forms of estrogens and androgens, namely, 17β-estradiol (E2), 16α,17β-estriol (E3), testosterone (TST) and dihydrotestosterone (DHT). Expression of these steroidogenic enzymes locally within various organs and tissues of the endocrine, reproductive, and central nervous systems is the key for maintaining high levels of the reproductive steroids. Thus, the enzymes have been drug targets for the prevention and treatment of diseases associated with steroid hormone excesses, especially in breast and prostate malignancies and endometriosis. Both AROM and STS have been the subjects of vigorous research for the past six decades. In this article, we review the procedures of their extraction and purification from human term placenta are described in detail, along with the activity assays.

Keywords:  Breast cancer; Conjugated steroid; DHEA; DHEA sulfate; Dehydroepiandrosterone; Dihydrotestosterone; Endometriosis; Estradiol; Estriol; Estrone; Estrone sulfate; Prostate cancer; Reproductive steroid; Sex steroid; Steroid sulfate; Testosterone

DOI:  https://doi.org/10.1016/bs.mie.2023.04.025
Nat Commun. 2023 Oct 12. 14(1): 6391

Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A.

Reetesh Raj Akhouri, Suchi Goel, Ulf Skoglund.

Placental malaria is caused by Plasmodium falciparum-infected erythrocytes (IEs) adhering to chondroitin sulfate proteoglycans in placenta via VAR2CSA-type PfEMP1. Human pentameric immunoglobulin M (IgM) binds to several types of PfEMP1, including VAR2CSA via its Fc domain. Here, a 3.6 Å cryo-electron microscopy map of the IgM-VAR2CSA complex reveals that two molecules of VAR2CSA bind to the Cµ4 of IgM through their DBL3X and DBL5ε domains. The clockwise and anti-clockwise rotation of the two VAR2CSA molecules on opposite faces of IgM juxtaposes C-termini of both VAR2CSA near the J chain, where IgM creates a wall between both VAR2CSA molecules and hinders its interaction with its receptor. To support this, we show when VAR2CSA is bound to IgM, its staining on IEs as well as binding of IEs to chondroitin sulfate A in vitro is severely compromised.

DOI: https://doi.org/10.1038/s41467-023-41838-x
Biochim Biophys Acta Mol Basis Dis. 2023 Oct 07. pii: S0925-4439(23)00279-X. [Epub ahead of print]1870(1): 166913

Exogenous recombinant N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) inhibits progression of B16F10 cutaneous melanomas and modulates cell signaling.

Sumit Bhattacharyya, Insug O-Sullivan, Jieqi Tu, Zhengjia Chen, Joanne K Tobacman.

  In the syngeneic, subcutaneous B16F10 mouse model of malignant melanoma, treatment with exogenous ARSB markedly reduced tumor size and extended survival. In vivo experiments showed that local treatment with exogenous N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) led to reduced tumor growth over time (p < 0.0001) and improved the probability of survival up to 21 days (p = 0.0391). Tumor tissue from the treated mice had lower chondroitin 4-sulfate (C4S) content and lower sulfotransferase activity. The free galectin-3 declined, and the SHP2 activity increased, due to altered binding with chondroitin 4-sulfate. These changes induced effects on transcription, which were mediated by Sp1, phospho-ERK1/2, and phospho-p38 MAPK. Reduced mRNA expression of chondroitin sulfate proteoglycan 4 (CSPG4), carbohydrate sulfotransferase 15 (N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase), and matrix metalloproteinases 2 and 9 resulted. Experiments in the human melanoma cell line A375 demonstrated similar responses to exogenous ARSB as in the tumors, and inverse effects followed ARSB siRNA. ARSB, which removes the 4-sulfate group at the non-reducing end of C4S, acts as a tumor suppressor, and treatment with exogenous ARSB impacts on vital cell signaling and reduces the expression of critical genes associated with melanoma progression.

Keywords:  Arylsulfatase B; CSPG4; Chondroitin sulfate; Melanoma; N-acetylgalactosamine-4-sulfatase

DOI:  https://doi.org/10.1016/j.bbadis.2023.166913
Int J Biol Macromol. 2023 Oct 04. pii: S0141-8130(23)03977-6. [Epub ahead of print]253(Pt 5): 127080

Biosynthesized silver nanoparticles-capped chondroitin sulfate nanogel targeting microbial infections and biofilms for biomedical applications.

Reham Yahya, Najwa M Alharbi.

  Medical devices are essential for patient care, but they can also serve as havens for dangerous microbes and the development of biofilm, which can lead to serious infections and higher death rates. To meet these issues, it is crucial to develop novel and effective antimicrobial coatings for medical devices. In this context, we have developed a new biofunctionalized nanosilver (ICS-Ag), employing itaconyl-chondroitin sulfate nanogel (ICSNG) as a synergistic reducing and stabilizing agent, to effectively eradicate microbial infections and biofilm formation. The antibacterial investigations showed that ICS-Ag nanocomposite is an intriguing antibiotic with excellent antibacterial indices (MIC/MBC (μg/mL): 2.29/4.58, 1.25/2.50, and 1.36/1.36 against S. aureus, E. coli, and P. aeruginosa, respectively), as well as antifungal capacity. Furthermore, ICS-Ag demonstrated efficacy superior to that of the antibiotic (ciprofloxacin, Cipro) against both Gram-positive and Gram-negative bacterial biofilms. TEM images of untreated and treated bacterial strains demonstrate synergistic actions that harm the bacterial cytomembrane, leading to the release of intracellular contents and bacterial death. Interestingly, ICS-Ag shows excellent biocompatibility, with an IC50 value (71.25 μg/mL) higher than MICs against tested microbes. Overall, the ICS-Ag film may provide multifunctional antimicrobial coatings for medical equipment to reduce microbial contamination and biofilm development.

Keywords:  Antimicrobial and anti-biofilm; Itaconyl-chondroitin sulfate nanogel; Nanosilver-loaded nanogel

DOI:  https://doi.org/10.1016/j.ijbiomac.2023.127080
Anal Sci. 2023 Oct 11.

Multicomponent analysis of dietary supplements containing glucosamine and chondroitin: comparative low- and high-field NMR spectroscopic study.

Klaudia Adels, Gereon Elbers, Bernd Diehl, Yulia Monakhova.

  With the prevalence of glucosamine- and chondroitin-containing dietary supplements for people with osteoarthritis in the marketplace, it is important to have an accurate and reproducible analytical method for the quantitation of these compounds in finished products. NMR spectroscopic method based both on low- (80 MHz) and high- (500-600 MHz) field NMR instrumentation was established, compared and validated for the determination of chondroitin sulfate and glucosamine in dietary supplements. The proposed method was applied for analysis of 20 different dietary supplements. In the majority of cases, quantification results obtained on the low-field NMR spectrometer are similar to those obtained with high-field 500-600 MHz NMR devices. Validation results in terms of accuracy, precision, reproducibility, limit of detection and recovery demonstrated that the developed method is fit for purpose for the marketed products. The NMR method was extended to the analysis of methylsulfonylmethane, adulterant maltodextrin, acetate and inorganic ions. Low-field NMR can be a quicker and cheaper alternative to more expensive high-field NMR measurements for quality control of the investigated dietary supplements. High-field NMR instrumentation can be more favorable for samples with complex composition due to better resolution, simultaneously giving the possibility of analysis of inorganic species such as potassium and chloride.

Keywords:  Chondroitin sulfate; Dietary supplements; Glucosamine; High-field NMR; Low-field NMR; Polysaccharides

DOI:  https://doi.org/10.1007/s44211-023-00433-2
J Exp Bot. 2023 Oct 13. pii: erad401. [Epub ahead of print]

Traits linked to natural variation of sulfur content in A. thaliana leaf.

Nicholas de Jager, Varsa Shukla, Anna Koprivova, Martin Lyčka, Lorina Bilalli, Yanrong You, Jürgen Zeier, Stanislav Kopriva, Daniela Ristova.

  Sulfur (S) is an essential mineral nutrient for plant growth and development, important for primary and specialized plant metabolites that are crucial for biotic and abiotic interactions. Foliar S content varies up to six-fold under controlled environment, suggesting an adaptive value under certain natural environmental conditions. However, a major quantitative regulator of S content in Arabidopsis thaliana has not been identified yet, pointing to the existence of additional genetic factors controlling sulfate/sulfur content or existence of many minor quantitative regulators. Here, we use overlapping information of two separate ionomics studies to select groups of accessions with low-, mid-, and high- foliar S content. We quantify series of metabolites, including anions (sulfate, phosphate, nitrate), thiols (cysteine, glutathione), seven glucosinolates, gene expression of twenty genes, sulfate uptake and three biotic traits. Our results suggest that S content is tightly connected with sulfate uptake, concentration of sulfate and phosphate anions, glucosinolate and glutathione synthesis. Additionally, our results indicate that the growth of pathogenic bacteria is enhanced in the A. thaliana accessions containing higher S in their leaf, suggesting complex regulation between S homeostasis, primary and secondary metabolism, and biotic pressures.

Keywords:   Arabidopsis thaliana ; Sulfur; gene expression; glucosinolates; glutathione; natural variation; nutrients

DOI:  https://doi.org/10.1093/jxb/erad401
Int J Biol Macromol. 2023 Oct 04. pii: S0141-8130(23)04025-4. [Epub ahead of print] 127128

Fabrication and optimization of multilayered composite scaffold made of sulfated alginate-based nanofiber/decellularized Wharton's jelly ECM for tympanic membrane tissue engineering.

Roghayeh Najafi, Fatemeh Yazdian, Mohamad Pezeshki-Modaress, Mina Aleemardani, Hadi Chahsetareh, Sajad Hassanzadeh, Mohammad Farhadi, Zohreh Bagher.

  In this study, we fabricated a novel multilayer polyvinyl alcohol (PVA)/alginate sulfate (ALG-S) nanofiber/decellularized Wharton's Jelly ECM (d-ECM) composite for tympanic membrane perforations (TMPs) tissue engineering (TE). Initially, electrospun PVA/ALG-S scaffolds with different blend ratios were fabricated. The influence of ALG-S ratio on surface morphology, mechanical, physical and biological properties of the nanofibers was studied. Secondly, 3-layer composites were developed as a combination of PVA/ALG-S nanofibers and d-ECM to take synergic advantages of electrospun mats and d-ECM. As part of the evaluation of the effects of d-ECM incorporation, the composite's mechanical properties, in vitro degradation, swelling ratio, and biological activities were assessed. The MTT assay showed that PVA/ALG-S nanofibers with 50:50 ratio provided a more desirable environment to support cell growth. A composite containing 25 mg/cm2 d-ECM was determined as the optimal composite through MTT assay, and this composite was used for animal studies inducing TMP regeneration. According to the in vivo studies, the optimal composite not only stimulated the healing of TMPs but also shortened the healing period. These results suggest that a multilayer nanofiber/hydrogel composite could be a potential platform for regenerating TMPs.

Keywords:  Alginate sulfate; Decellularized Wharton's jelly extracellular matrix; Electrospinning; Tissue engineering; Tympanic membrane perforations

DOI:  https://doi.org/10.1016/j.ijbiomac.2023.127128
FASEB Bioadv. 2023 Oct;5(10): 377-394

A combination of 5/6-nephrectomy and unilateral ureteral obstruction model accelerates progression of remote organ fibrosis in chronic kidney disease.

Kyoka Homma, Yuki Enoki, Sato Uchida, Kazuaki Taguchi, Kazuaki Matsumoto.

  Chronic kidney disease (CKD) involves progressive renal fibrosis, which gradually reduces kidney function and often causes various complications in extrarenal tissues. Therefore, we investigated fibrogenesis in extrarenal tissues (heart, liver, and lungs) in different experimental CKD models, such as the 5/6-nephrectomy (5/6 Nx), unilateral ureteral obstruction (UUO), and a combination (2/3 Nx + UUO). We evaluated the degree of fibrogenesis in kidneys and extrarenal tissues by histological analysis and quantification of fibrosis-related gene and protein expression. To elucidate the fibrosis mechanisms observed in 2/3 Nx + UUO mice, we evaluated the effect of indoxyl sulfate (IS), a typical uremic toxin accumulated in CKD, and transforming growth factor-β (TGF-β), a fibrosis-related factor, on fibrosis using human hepatoma (HepG2) and RAW264.7 cells. A significant decline in renal function was observed in the 5/6 Nx and 2/3 Nx + UUO models, whereas a significant increase in renal fibrosis was observed only in the obstructed kidneys. Notable amount of fibrosis was induced in the liver and heart in the 2/3 Nx + UUO model, with the induction of macrophage infiltration and increased tissue IS and TGF-β levels. In agreement with the results of in vivo experiments, co-stimulation with IS, TGF-β, and macrophage-conditioned medium increased the expression of fibrogenic genes in HepG2 cells. We demonstrated that the 2/3 Nx + UUO model induced both loss of renal function and renal fibrosis in the earlier stages, providing a novel CKD model that induces remote organ fibrosis in a shorter time.

Keywords:  chronic kidney disease; extrarenal tissue; fibrosis; indoxyl sulfate; transforming growth factor‐β; uremic toxin

DOI:  https://doi.org/10.1096/fba.2023-00045
Int J Mol Sci. 2023 Sep 27. pii: 14621. [Epub ahead of print]24(19):

p-Cresol Sulfate Is a Sensitive Urinary Marker of Fecal Microbiota Transplantation and Antibiotics Treatments in Human Patients and Mouse Models.

Yuyin Zhou, Zheting Bi, Matthew J Hamilton, Li Zhang, Rui Su, Michael J Sadowsky, Sabita Roy, Alexander Khoruts, Chi Chen.

  Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) and also a potential therapy for other diseases associated with dysbiotic gut microbiota. Monitoring metabolic changes in biofluids and excreta is a noninvasive approach to identify the biomarkers of microbial recolonization and to understand the metabolic influences of FMT on the host. In this study, the pre-FMT and post FMT urine samples from 11 rCDI patients were compared through metabolomic analyses for FMT-induced metabolic changes. The results showed that p-cresol sulfate in urine, a microbial metabolite of tyrosine, was rapidly elevated by FMT and much more responsive than other microbial metabolites of aromatic amino acids (AAAs). Because patients were treated with vancomycin prior to FMT, the influence of vancomycin on the microbial metabolism of AAAs was examined in a mouse feeding trial, in which the decreases in p-cresol sulfate, phenylacetylglycine, and indoxyl sulfate in urine were accompanied with significant increases in their AAA precursors in feces. The inhibitory effects of antibiotics and the recovering effects of FMT on the microbial metabolism of AAAs were further validated in a mouse model of FMT. Overall, urinary p-cresol sulfate may function as a sensitive and convenient therapeutic indicator on the effectiveness of antibiotics and FMT for the desired manipulation of gut microbiota in human patients.

Keywords:  antibiotics; aromatic amino acid; fecal microbiota transplantation; gut microbiota; metabolomics; microbial metabolism; p-cresol sulfate

DOI:  https://doi.org/10.3390/ijms241914621
Drug Test Anal. 2023 Oct 08.

Brief history of the alcohol biomarkers CDT, EtG, EtS, 5-HTOL, and PEth.

Alan Wayne Jones.

  This article traces the historical development of various biomarkers of acute and/or chronic alcohol consumption. Much of the research in this domain of clinical and laboratory medicine arose from clinics and laboratories in Sweden, as exemplified by carbohydrate deficient transferrin (CDT) and phosphatidylethanol (PEth). Extensive studies of other alcohol biomarkers, such as ethyl glucuronide (EtG), ethyl sulfate (EtS), and 5-hydroxytryptophol (5-HTOL), also derive from Sweden. The most obvious test of recent drinking is identification of ethanol in a sample of the person's blood, breath, or urine. However, because of continuous metabolism in the liver, ethanol is eliminated from the blood at a rate of 0.15 g/L/h (range 0.1-0.3 g/L/h), so obtaining positive results is not always possible. The widow of detection is increased by analysis of ethanol's non-oxidative metabolites (EtG and EtS), which are more slowly eliminated from the bloodstream. Likewise, an elevated ratio of serotonin metabolites in urine (5-HTOL/5-HIAA) can help to disclose recent drinking after ethanol is no longer measurable in body fluids. A highly specific biomarker of hazardous drinking is CDT, a serum glycoprotein (transferrin), with a deficiency in its N-linked glycosylation. Another widely acclaimed biomarker is PEth, an abnormal phospholipid synthesized in cell membranes when people drink excessively, having a long elimination half-life (median ~6 days) during abstinence. Research on the subject of alcohol biomarkers has increased appreciably and is now an important area of drug testing and analysis.

Keywords:  alcohol biomarkers; carbohydrate deficient transferrin; ethyl glucuronide; ethyl sulfate; phosphatidylethanol

DOI:  https://doi.org/10.1002/dta.3584
Nutrients. 2023 Oct 05. pii: 4264. [Epub ahead of print]15(19):

The Acute Effect of Hydroxychloroquine Sulfate on Hunger, the Plasma Concentration of Orexigenic Peptides and Hedonic Food Intake: A Pilot Study.

Emily Ruilova Sosoranga, Wout Verbeure, Hannelore Geysen, Theo Thijs, Christophe Matthys, Inge Depoortere, Jan Tack.

  The direct infusion of bitter solutions in the gastrointestinal tract can reduce the secretion of orexigenic hormones and influence appetite and food intake. We aimed to explore whether oral ingestion of the bitter tastant hydroxychloroquine sulfate can exert similar effects. Ten lean adult women were included in this double-blind, randomized, two-visit, crossover study. After an overnight fast, each volunteer received film-coated tablets containing 400 mg of hydroxychloroquine sulfate (Plaquenil®) or placebo. Plasma-ghrelin, -motilin, -insulin and blood-glucose concentrations were determined every 10 min before and 30 min after feeding; appetite was scored every 10 min. Hunger scores were investigated with a special interest 50-60 min after the ingestion of hydroxychloroquine sulfate, right before a rewarding chocolate milkshake was offered to drink ad libitum. Compared with the placebo, hydroxychloroquine sulfate tended to reduce hunger at the time of interest (p = 0.10). No effect was found upon subsequent milkshake intake. Motilin plasma concentrations were unaltered, but acyl-ghrelin plasma concentrations decreased after the ingestion of hydroxychloroquine sulfate (t = 40-50; p < 0.05). These data suggest that the oral intake of hydroxychloroquine sulfate tablets reduces subjective hunger via a ghrelin-dependent mechanism but does not affect motilin release, hedonic food intake or insulin levels in healthy women.

Keywords:  Plaquenil®; appetite; bitter; fasting; ghrelin; hydroxychloroquine sulfate; motilin; quinine

DOI:  https://doi.org/10.3390/nu15194264
Acute Med Surg. 2023 Jan-Dec;10(1):10(1): e896

The endothelial glycocalyx-All the same? No, it is not.

Kodai Suzuki, Tomotaka Miura, Hideshi Okada.

  The endothelial glycocalyx covers the lumen of blood vessels throughout the body and plays an important role in endothelial homeostasis. Advances in electron microscopy techniques have provided clues to better understand the structure and composition of identical vascular endothelial glycocalyx. The morphology and thickness of the endothelial glycocalyx differ from organ to organ. The content of the endothelial glycocalyx covering the vascular lumen differs even in the brain, heart, and lungs, which have the same continuous capillaries. Various types of inflammation are known to attenuate the endothelial glycocalyx; however, we found that the morphology of the glycocalyx damaged by acute inflammation differed from that damaged by chronic inflammation. Acute inflammation breaks the endothelial glycocalyx unevenly, whereas chronic inflammation leads to the overall shortening of the endothelial glycocalyx. The same drug has different effects on the endothelial glycocalyx, depending on the location of the target blood vessels. This difference in response may reflect not only the size and shape of the endothelial glycocalyx but also the different constituents. In the cardiac tissue, the expression of glypican-1, a core protein of the endothelial glycocalyx, was enhanced. By contrast, in the pulmonary tissue, the expression of heparan sulfate 6-O-sulfotransferase 1 and endothelial cell-specific molecule-1 significantly increased in the treatment group compared with that in the no-treatment group. In this review, we present the latest findings on the evolution of the vascular endothelial glycocalyx and consider the microstructural differences.

Keywords:  electron microscopy; endothelial cell injury; endothelial homeostasis; glycocalyx; microstructural differences

DOI:  https://doi.org/10.1002/ams2.896