bims-supasi 2024-01-21 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2024–01–21
thirteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Multi-step semi-synthesis, structural characterization and growth factor interaction study of regiochemically sulfated diabolican polysaccharides.
Chondroitin sulfate and caseinophosphopeptides doped polyurethane-based highly porous 3D scaffolds for tendon-to-bone regeneration.
Associations of Indoxyl Sulfate and p-cresyl Sulfate with Serum Uncarboxylated Matrix γ-carboxyglutamate Protein in Chronic Kidney Disease Patients.
Can our microbiome break our hearts? Collaborative production of p-cresol sulfate and indoxyl sulfate by commensal microbes increases susceptibility to thrombosis.
Preparation and characterization of sulfated nanocellulose: From hydrogels to highly transparent films.
Biomarkers of Glycosaminoglycans (GAG) accumulation in patients with mucopolysaccharidosis type VI-LeukoGAG, Corneal Opacification (COM) and Carotid Intima Media Thickening (CIMT).
Hippo Cell Signaling and HS-Proteoglycans Regulate Tissue Form and Function, Age-dependent Maturation, Extracellular Matrix Remodelling and Repair.
Urinary Androgens Provide Additional Evidence Related to Metabolism and Are Correlated With Serum Androgens in Girls.
Pharmacokinetics of Hydroxytyrosol and Its Sulfate and Glucuronide Metabolites after the Oral Administration of Table Olives to Sprague-Dawley Rats.
Investigating alcohol consumption in China via wastewater-based epidemiology.
A low-anticoagulant heparin suppresses metastatic dissemination through the inhibition of tumor cell-platelets association.
Prenatal paternal anxiety symptoms predict child DHEA levels and internalizing symptoms during adrenarche.
Simultaneous determination of colistin sulfate and tigecycline in human plasma by liquid chromatography-tandem mass spectrometry method.

Int J Biol Macromol. 2024 Jan 17. pii: S0141-8130(24)00286-1. [Epub ahead of print] 129483

Multi-step semi-synthesis, structural characterization and growth factor interaction study of regiochemically sulfated diabolican polysaccharides.

Fabiana Esposito, Corinne Sinquin, Sylvia Colliec-Jouault, Stéphane Cuenot, Martine Pugnière, Giang Ngo, Serena Traboni, Agata Zykwinska, Emiliano Bedini.

  Diabolican is an exopolysaccharide (EPS) produced by Vibrio diabolicus HE800, a mesophilic bacterium firstly isolated from a deep-sea hydrothermal field. Its glycosaminoglycan (GAG)-like structure, consisting of a tetrasaccharide repeating unit composed of two aminosugars (N-acetyl-glucosamine and N-acetyl-galactosamine) and two glucuronic acid units, suggested to subject it to regioselective sulfation processes, in order to obtain some sulfated derivatives potentially acting as GAG mimics. To this aim, a multi-step semi-synthetic approach, relying upon tailored sequence of regioselective protection, sulfation and deprotection steps, was employed in this work. The chemical structure of the obtained sulfated diabolican derivatives was characterized by a multi-technique analytic approach, in order to define both degree of sulfation (DS) and sulfation pattern within the polysaccharide repeating unit, above all. Finally, binding affinity for some growth factors relevant for biomedical applications was measured for both starting diabolican and sulfated derivatives thereof. Collected data suggested that sulfation pattern could be a key structural element for the selective interaction with signaling proteins not only in the case of native GAGs, as already known, but also for GAG-like structures obtained by regioselective sulfation of naturally unsulfated polysaccharides.

Keywords:  Growth factors; Marine polysaccharides; Multi-step semi-synthesis; Regioselectivity; Sulfation

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.129483
Int J Pharm. 2024 Jan 17. pii: S0378-5173(24)00056-5. [Epub ahead of print] 123822

Chondroitin sulfate and caseinophosphopeptides doped polyurethane-based highly porous 3D scaffolds for tendon-to-bone regeneration.

Eleonora Bianchi, Marco Ruggeri, Elena Del Favero, Roberto Pisano, Fiora Artusio, Caterina Ricci, Barbara Vigani, Anita Ferraretto, Cinzia Boselli, Antonia Icaro Cornaglia, Silvia Rossi, Giuseppina Sandri.

  Tendon disorders are common injuries, which can be greatly debilitating as they are often accompanied by great pain and inflammation. Moreover, several problems are also related to the laceration of the tendon-to-bone interface (TBI), a specific region subjected to great mechanical stresses. The techniques used nowadays for the treatment of tendon and TBI injuries often involve surgery. However, one critical aspect of this procedure involves the elevated risk of fail due to the tissues weakening and the postoperative alterations of the normal joint mechanics. Synthetic polymers, such as thermoplastic polyurethane, are of special interest in the tissue engineering field as they allow the production of scaffolds with tunable elastic and mechanical properties, that could guarantee an effective support during the new tissue formation. Based on these premises, the aim of this work was the design and the development of highly porous 3D scaffolds based on thermoplastic polyurethane, and doped with chondroitin sulfate and caseinophosphopeptides, able to mimic the structural, biomechanical, and biochemical functions of the TBI. The obtained scaffolds were characterized by a homogeneous microporous structure, and by a porosity optimal for cell nutrition and migration. They were also characterized by remarkable mechanical properties, reaching values comparable to the ones of the native tendons. The scaffolds promoted the tenocyte adhesion and proliferation when caseinophosphopetides and chondroitin sulfate are present in the 3D structure. In particular, caseinophosphopeptides' optimal concentration for cell proliferation resulted 2.4 mg/mL. Finally, the systems evaluation in vivo demonstrated the scaffolds' safety, since they did not cause any inflammatory effect nor foreign body response, representing interesting platforms for the regeneration of injured TBI.

Keywords:  AFM; caseinophosphopeptides; chondroitin sulfate; mechanical properties; tendon disorders; thermoplastic polyurethane

DOI:  https://doi.org/10.1016/j.ijpharm.2024.123822
Curr Med Chem. 2024 Jan 12.

Associations of Indoxyl Sulfate and p-cresyl Sulfate with Serum Uncarboxylated Matrix γ-carboxyglutamate Protein in Chronic Kidney Disease Patients.

Xiaofang Tang, Di Liu, Ming Xia, Yu Liu, Hong Liu.

   BACKGROUND: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are two important protein-bound uremic retention solutes. Increased serum levels of IS and PCS are associated with cardiovascular calcification. Matrix γ-carboxyglutamate protein (MGP) is a potent inhibitor of vascular calcification and inactivated uncarboxylated MGP (ucMGP) is related to vascular calcification. Nevertheless, whether serum levels of IS and PCS are associated with the serum ucMGP level in chronic kidney disease (CKD) patients with different stages is unknown.
METHOD: This cross-sectional study enrolled 90 patients in different stages of chronic kidney disease. Serum levels of IS and PCS were determined. The serum concentration of ucMGP was measured with an enzyme-linked immunosorbent assay. Independent associations between serum total IS and PCS with ucMGP were evaluated.
RESULTS: The mean serum level of ucMGP in participants of this study is 10.78±5.22 μg/mL. Serum levels of the two above-mentioned uremic toxins and ucMGP were elevated commensurately with deteriorating renal function. The serum level of ucMPG was associated with total IS (r = 0.456, p < 0.001) and total PCS (r =0.413, p < 0.001) levels. Multiple linear regression analysis showed that ucMGP was significantly related to levels of IS (β = 0.442, p <0.001), but not the level of PCS concentrations after adjusting for other confounding variables.
CONCLUSION: Our study showed that a higher serum IS level was independently associated with ucMGP in deteriorating CKD. Therefore, it would be worthwhile to investigate the effect of IS on ucMGP in the pathogenesis of vascular calcification in future studies.

Keywords:  Indoxyl sulfate; chronic kidney disease; p-cresyl sulfate; patients.; uncarboxylated MGP; vascular calcification

DOI:  https://doi.org/10.2174/0109298673272856231225173757
mBio. 2024 Jan 16. e0269223

Can our microbiome break our hearts? Collaborative production of p-cresol sulfate and indoxyl sulfate by commensal microbes increases susceptibility to thrombosis.

Tamara R Machado Ribeiro, Camila B Brito, Mariana X Byndloss.

  A recent study published in mBio by Nemet et al. revealed the critical role played by two gut microbiota members in producing the metabolites indoxyl sulfate (IS) and p-cresol sulfate (pCS) (I. Nemet, M. Funabashi,X. S. Li, M. Dwidar, et al., 2023, mBio 14:e01331-23, https://doi.org/10.1128/mbio.01331-23). Understanding microbial pathways leading to IS and pCS production is crucial because they are connected to a pre-thrombotic profile, and having high levels of these metabolites increases the risk of cardiovascular diseases (CVD). Hence, this study can offer vital insights into assessing the risk for CVD and identifying potential treatment targets for this disease.

Keywords:  metabolites; microbiota; thrombosis

DOI:  https://doi.org/10.1128/mbio.02692-23
Int J Biol Macromol. 2024 Jan 15. pii: S0141-8130(24)00267-8. [Epub ahead of print] 129464

Preparation and characterization of sulfated nanocellulose: From hydrogels to highly transparent films.

Mohamed Jaouahar, El-Houssaine Ablouh, Zouhair Hanani, Blaž Jaklič, Matjaz Spreitzer, Fatima-Zahra Semlali, Anass Ait Benhamou, Youssef Samih, Mounir El Achaby, Houssine Sehaqui.

  This study focuses on the production of sulfated cellulose microfibers and nanocellulose hydrogels from native cellulose microfibers (CMF). The process involves using a combination of H2SO4 and urea, resulting in highly sulfated cellulose microfiber hydrogel (SC) with notable properties such as a sulfur content of 7.5 %, a degree of sulfation of 0.49, a surface charge content of 2.2 mmol. g-1, and a high yield of 81 %. The SC hydrogel can be easily fibrillated into sulfated nanocellulose hydrogel (S-NC) with elongated nanocellulose structures having an average diameter of 6.85 ± 3.11 nm, as determined using atomic force microscopy (AFM). X-ray photoelectron spectroscopy (XPS) analysis confirms the presence of sulfate groups on the surface of the nanocellulose material. Transparent films with good mechanical properties can be produced from both cellulose microfiber and nanocellulose hydrogels. The sulfate functionality gives the hydrogel attractive rheological properties and makes S-NC re-dispersible in water, which can be beneficial for various applications. This study demonstrates the potential of this process to address previous challenges related to nanocellulose materials production.

Keywords:  Hydrogel; Nanocellulose; Polysaccharide Sulfation

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.129464
Mol Genet Metab Rep. 2024 Mar;38 101041

Biomarkers of Glycosaminoglycans (GAG) accumulation in patients with mucopolysaccharidosis type VI-LeukoGAG, Corneal Opacification (COM) and Carotid Intima Media Thickening (CIMT).

Young Bae Sohn, Raymond Wang, Jane Ashworth, Pierre Broqua, Mireille Tallandier, Jean-Louis Abitbol, Erin Jozwiak, Laura Pollard, Timothy C Wood, Tariq Aslam, Paul R Harmatz.

  Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal storage disorder characterized by deficient activity of arylsulfatase B enzyme (ASB) resulting in cellular accumulation of dermatan sulfate (DS) and chondroitin sulfate (CS) that leads to cell injury. Urinary glycosaminoglycans (GAG) are often used as a biomarker in MPS diseases for diagnosis and to monitor treatment efficacy. This study evaluated leukocyte GAGs (leukoGAG) and skin GAGs as alternate biomarkers representing intracellular GAG changes in patients with MPS VI and treated with enzyme replacement therapy (ERT). In addition, we evaluated corneal opacification measurements (COM) and carotid intima media thickness (CIMT) as indicators of GAG accumulation and tissue injury. The study was performed in a serial two-step design in a single center. A quantitative method to measure leukoGAG levels in leukocytes was developed in Study 1 to compare the GAG levels between MPS VI patients and a control group and to assess correlations between leukoGAG and urineGAG. Study 2 validated the leukoGAG measurement, assessed the effect of ERT infusion on leukoGAG and ASB activity in leukocytes, identified correlations between leukoGAG and other biomarkers, and assessed differences in GAG accumulation between MPS VI patients and control subjects. In Study 1, leukoCS and leukoDS levels were significantly higher in the MPS VI group than the control group (leukoCS: 37.9 ± 10.2 and 2.9 ± 1.5 μg/μg protein, respectively, p = 0.005; leukoDS: 0.26 ± 0.2 and 0.0 ± 0.0 μg/μg protein, respectively, p = 0.028) with positive correlations between leukoCS and urine CS and leukoDS and urineDS. In Study 2, leukoCS (32.0 ± 11.8 vs 6.9 ± 3.1 μg/mg protein, p = 0.005) and leukoDS (0.4 ± 0.1 and 0.2 ± 0.1 μg/mg protein, p = 0.020) were significantly higher compared with control subjects. Thus, these results highlight the potential of leukoGAG as a new biomarker representing intracellular GAG accumulation in MPS VI patients and may be valuable for patient management.

Keywords:  Carotid intima media thickness; Corneal opacification measurements; Leukocyte GAG; Mucopolysaccharidosis type VI; Skin GAG

DOI:  https://doi.org/10.1016/j.ymgmr.2023.101041
Am J Physiol Cell Physiol. 2024 Jan 15.

Hippo Cell Signaling and HS-Proteoglycans Regulate Tissue Form and Function, Age-dependent Maturation, Extracellular Matrix Remodelling and Repair.

James Melrose.

  This review examined how Hippo cell signaling and HS-proteoglycans (HSPGs) regulate tissue form and function. Despite being a non-weight bearing tissue the brain is regulated by Hippo mechanoresponsive cell signalling pathways during embryonic development. HS-proteoglycans interact with growth factors, morphogens and extracellular matrix components to regulate development and pathology. Pikachurin and Eyes Shut interact with dystroglycan to stabilize the photoreceptor axoneme primary cilium and ribbon synapse facilitating phototransduction and neurotransduction with bipolar retinal neuronal networks in ocular vision, the primary human sense. Another HSPG, Neurexin interacts with structural and adaptor proteins to stabilize synapses and ensure specificity of neural interactions, and aids in synaptic potentiation and plasticity in neurotransduction. HSPGs also stabilize the blood brain barrier and motor neuron basal structures in the neuromuscular junction. Agrin and perlecan localize acetylcholinesterase and its receptors in the neuromuscular junction essential for neuromuscular control. The primary cilium is a mechanosensory hub on neurons, utilized by YAP-TAZ Hippo, Hh, Wnt, TGF-b/BMP receptor tyrosine kinase cell signaling. Members of the glypican HSPG proteoglycan family interact with Smoothened and Patched G-protein coupled receptors on the cilium to regulate Hh and Wnt signaling during neuronal development. Control of glycosyl sulfotransferases and endogenous protease expression by Hippo TAZ YAP represents a mechanism whereby the fine structure of HS-proteoglycans can be potentially modulated spatio-temporally to regulate tissue morphogenesis in a similar manner to how Hippo signaling controls sialyltransferase expression and mediation of cell-cell recognition, dysfunctional sialic acid expression is a feature of many tumors.

Keywords:  CNS/PNS; Heparan sulfate proteoglycans; Hippo cell signalling; TAZ; YAP

DOI:  https://doi.org/10.1152/ajpcell.00683.2023
J Endocr Soc. 2024 Jan 16. 8(3): bvad161

Urinary Androgens Provide Additional Evidence Related to Metabolism and Are Correlated With Serum Androgens in Girls.

Sasinya N Scott, Marvin Siguencia, Frank Z Stanczyk, Michaela F Hartmann, Stefan A Wudy, Melissa White, Wendy K Chung, Regina M Santella, Mary Beth Terry, Lauren C Houghton.

   Context: Androgen levels are generally measured in serum samples, but urine may be a more feasible option, especially in children, as it is a noninvasive alternative.
Objective: To assess the correlations of 10 urinary androgen metabolites with 4 serum androgens [dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, and total and free testosterone] and assess if their correlations differ by participant characteristics.
Methods: Our study consisted of 44 girls, ages 6-13, who participated in the New York site of the LEGACY Girls Study and had both serum and urine samples collected at the same visit. We performed Pearson's correlation coefficient tests between 4 serum and 10 individual urinary metabolite measures and their sum. We examined the influence of participant characteristics on the magnitude and direction of the correlations.
Results: The summed urinary metabolite measures had the highest correlation with free testosterone in serum (global sum, r = 0.83) and correlated least with DHEA-S in serum (global sum, r = 0.64). The correlation between individual urinary metabolites and serum androgens ranged from 0.08 to 0.84.Two 11-oxygenated urinary metabolites (5α-androstane-3α-ol-11,17-dione5β-androstane-3α,11β-diol-17-one) were weakly correlated with all serum androgens. Participant age, weight, height, waist:hip ratio, and pubic hair growth stage changed the correlations between urinary and serum androgens measures between 10% and 213%.
Conclusion: The sum of urinary androgen metabolites was a good marker of circulating androstenedione, testosterone, and free testosterone. Individual urinary metabolites provide additional information about the metabolic processes of disease development compared to the antecedent serum androgens.

Keywords:  adolescents; androgens; metabolites; puberty; serum; urine

DOI:  https://doi.org/10.1210/jendso/bvad161
J Agric Food Chem. 2024 Jan 17.

Pharmacokinetics of Hydroxytyrosol and Its Sulfate and Glucuronide Metabolites after the Oral Administration of Table Olives to Sprague-Dawley Rats.

Ivana Kundisová, Helena Colom, M Emília Juan, Joana M Planas.

  The pharmacokinetics (PK) of hydroxytyrosol and its metabolites were characterized following oral administration to Sprague-Dawley rats of 3.85 and 7.70 g of destoned Arbequina table olives/kg. Plasma samples were analyzed using a fully validated method consisting of liquid extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Noncompartmental PK analysis of hydroxytyrosol demonstrated linear PK between doses of 2.95 and 5.85 mg hydroxytyrosol/kg. Half-life was approximately 2.5 h, while mean residence time was around 4 h. Clearance occurred by conversion to two sulfate and two glucuronide conjugates. The area under the plasma concentration-time curve (AUC) ratios of metabolites versus parent hydroxytyrosol was approximately 7-9-fold for the sulfate and below 0.25 for the glucuronide, indicating sulfation as the predominant metabolic pathway. Despite extensive metabolism, hydroxytyrosol remained in plasma for up to 8 h with AUCs of 4293 and 8919 min·nmol/L for the doses of 3.85 and 7.70 g/kg, respectively. Therefore, table olives provide a more sustained plasma profile than other foods containing hydroxytyrosol, which may enhance its health-protecting activities.

Keywords:  Arbequina table olives; hydroxytyrosol; hydroxytyrosol glucuronide; hydroxytyrosol sulfate; noncompartmental analysis

DOI:  https://doi.org/10.1021/acs.jafc.3c06431
Environ Geochem Health. 2024 Jan 15. 46(1): 24

Investigating alcohol consumption in China via wastewater-based epidemiology.

Yan Yao, Jingya Wang, Yuling Zhong, Wenyu Chen, Yulan Rao, Mengxiang Su.

  Alcohol abuse and addiction is a public health issue of global concern. Wastewater-based epidemiology (WBE) is a forceful and effective complementary tool for investigating chemical consumption. This study examined alcohol consumption in major cities of China via WBE and compared WBE estimates with other data sources. A simple and valid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of two alcohol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS) in wastewater. The optimized method was applied to 62 sewage samples collected from wastewater treatment plants (WWTPs) in 31 provincial capital cities across China in the fourth quarter of 2020. The methodology established in this study was validated with the lower limit of quantification (LLOQ) up to 0.1 μg/L, good linearity in the range of 0.1-50 μg/L, intra-day and inter-day precision less than 5.58% and 5.55%, respectively, and the recoveries of the extracts were higher than 97.14%. The consumption range of alcohol estimated via WBE was 6.09 ± 4.56 ethanol/person/day (EPD) in the capital cities of China. Alcohol consumption varies significantly between cities in China, with WBE estimating lower alcohol consumption than WHO and lower than foreign countries. Investing in alcohol consumption based on WBE has great potential to accurately and efficiently estimate alcohol consumption.

Keywords:  Alcohol; Ethyl sulfate; UPLC-MS/MS; Wastewater-based epidemiology

DOI:  https://doi.org/10.1007/s10653-023-01829-9
Biomed Pharmacother. 2024 Jan 12. pii: S0753-3322(23)01906-6. [Epub ahead of print]171 116108

A low-anticoagulant heparin suppresses metastatic dissemination through the inhibition of tumor cell-platelets association.

Juliana M Motta, Kayene V A Micheli, Carlos Roberto-Fernandes, Michelle Hermsdorff-Brandt, Alessandra L Guedes, Flávia S Frattani, Paulo A S Mourão, Mariana S Pereira.

  Metastasis is the leading cause of cancer-related deaths. Despite this relevance, there is no specific therapy targeting metastasis. The interaction of the tumor cell with platelets, forming microemboli is crucial for successful hematogenous dissemination. Heparin disrupts it by a P-selectin-mediated event. However, its clinical use for this purpose is hindered by the requirement of high doses, leading to anticoagulant-related side effects. In this study, we obtained a low-anticoagulant heparin through the fractionation of a pharmaceutical bovine heparin. This derivative was referred to as LA-hep and we investigated its efficacy in inhibiting metastases and explored its capacity of suppressing the interaction between tumor cells and platelets. Our data revealed that LA-hep is as efficient as porcine unfractionated heparin in attenuating lung metastases from melanoma and colon adenocarcinoma cells in an assay with a single intravenous administration. It also prevents platelet arrest shortly after cell injection in wild-type mice and suppresses melanoma-platelets interaction in vitro. Moreover, LA-hep blocks P-selectin's direct binding to tumor cells and platelet aggregation, providing further evidence for the role of P-selectin as a molecular target. Even in P-selectin-depleted mice which developed a reduced number of metastatic foci, both porcine heparin and LA-hep further inhibited metastasis burden. This suggests evidence of an additional mechanism of antimetastatic action. Therefore, our results indicate a dissociation between the heparin anticoagulant and antimetastatic effects. Considering the simple and highly reproducible methodology used to purify LA-hep along with the data presented here, LA-hep emerges as a promising drug for future use in preventing metastasis in cancer patients.

Keywords:  Heparin; Metastasis; P-selectin; Platelets; Tumor cells

DOI:  https://doi.org/10.1016/j.biopha.2023.116108
Front Behav Neurosci. 2023 ;17 1217846

Prenatal paternal anxiety symptoms predict child DHEA levels and internalizing symptoms during adrenarche.

Sherri Lee Jones, Victoria De Braga, Christina Caccese, Jimin Lew, Guillaume Elgbeili, Natalie Castellanos-Ryan, Sophie Parent, Gina Muckle, Catherine M Herba, William D Fraser, Simon Ducharme, Julia Barnwell, Jacquetta Trasler, Jean R Séguin, Tuong-Vi Nguyen, Tina C Montreuil.

   Introduction: This study examined (1) whether measures of paternal anxious and depressive symptoms collected prenatally and during a follow-up assessment when the child was in middle childhood, predict child neuroendocrine outcomes, and (2) whether neuroendocrine outcomes are intermediate factors between paternal mental health and child cognitive/behavioral outcomes. Middle childhood coincides with increased autonomy as the child transitions into grade school, and with adrenarche, as the maturing adrenal gland increases secretion of dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEA-S), hormones that are implicated in corticolimbic development which regulate emotions and cognition.
Methods: Participants were recruited from a subsample of a large prospective birth cohort study (3D study). We conducted a follow-up study when children were 6-8 years old (N = 61 families, 36 boys, 25 girls). Parental symptoms of anxiety, stress and depression were assessed via validated self-report questionnaires: prenatally using an in-house anxiety questionnaire, the Perceived Stress Scale (PSS) and the Center for Epidemiologic Studies Depression (CES-D), and at the follow up, using the Beck Anxiety and Beck Depression Inventories. Children provided salivary hormone samples, and their pituitary gland volume was measured from structural Magnetic Resonance Imaging (MRI) scans. Child behaviors were measured using the Strengths and Difficulties Questionnaire and cognitive outcomes using the WISC-V. Multiple regression analyses were used to test whether paternal mental health symptoms assessed prenatally and during childhood are associated with child neuroendocrine outcomes, adjusting for maternal mental health and child sex. Indirect-effect models assessed whether neuroendocrine factors are important intermediates that link paternal mental health and cognitive/behavioral outcomes.
Results: (1) Fathers' prenatal anxiety symptoms predicted lower DHEA levels in the children, but not pituitary volume. (2) Higher prenatal paternal anxiety symptoms predicted higher child internalizing symptoms via an indirect pathway of lower child DHEA. No associations were detected between paternal anxiety symptoms measured in childhood, and neuroendocrine outcomes. No child sex differences were detected on any measure.
Conclusion: These results highlight the often-overlooked role of paternal factors during pregnancy on child development, suggesting that paternal prenatal anxiety symptoms are associated with child neuroendocrine function and in turn internalizing symptoms that manifest at least up to middle childhood.

Keywords:  DHEA; MRI; child development; internalizing; middle childhood; neuroendocrine; paternal mental health; pituitary

DOI:  https://doi.org/10.3389/fnbeh.2023.1217846
BMC Chem. 2024 Jan 13. 18(1): 12

Simultaneous determination of colistin sulfate and tigecycline in human plasma by liquid chromatography-tandem mass spectrometry method.

Ying-Chao Ma, Xi-Kun Wu, Xiu-Ling Yang, Zhi-Qing Zhang.

   OBJECTIVE: To establish a high-performance liquid chromatography-tandem mass spectrometry method (HPLC-MS/MS) to simultaneously determine colistin sulfate and tigecycline in human plasma.
METHODS: Polymyxin B1 internal standard (20 µL) was added into 200 µL of plasma sample. The samples were treated with methanol-5% trichloroacetic acid (50:50, V/V) solution, and the protein precipitation method was adopted for post-injection analysis. The chromatographic column was a Dikma C18 (4.6 mm × 150 mm, 5 μm). For the mobile phase, 0.1% formic acid in aqueous solution was used for phase A, 0.1% formic acid in acetonitrile solution for phase B, and gradient elution was also applied. The flow rate was 0.8 mL/min, the column temperature was 40 °C, and the injection volume was 10 µL; Electrospray ionization and multiple reaction ion monitoring were adopted and scanned by the HPLC-MS/MS positive ion mode.
RESULTS: The endogenous impurities in the plasma had no interference in the determination of the analytes. There existed a good linear relationship of colistin sulfate within the range of 0.1-10 µg/mL (R2 = 0.9986), with the lower limit of quantification (LLOQ) of 0.1 µg/mL. There existed a good linear relationship of tigecycline within the range of 0.05-5 µg/ mL (R2 = 0.9987), with the LLOQ of 0.05 µg/mL. The intra- and inter-day relative standard deviations of colistin sulfate and tigecycline were both less than 15%, and the accuracy was between 88.21% and 108.24%. The extraction had good stability, the extraction recovery rate was 87.75-91.22%, and the matrix effect was 99.40-105.26%.
CONCLUSION: This study successfully established a method for simultaneously detecting colistin sulfate and tigecycline plasma concentrations. The method was simple, rapid, and highly sensitive and could be applied for therapeutic medication monitoring.

Keywords:  Colistin sulfate; Liquid chromatography–tandem mass spectrometry; Plasma drug concentration; Therapeutic medication monitoring; Tigecycline

DOI:  https://doi.org/10.1186/s13065-023-01109-8