Probing the Magnetic Anisotropy of Co(II) Complexes Featuring Redox-Active Ligands

Coordination complexes that possess large magnetic anisotropy (otherwise known as zero-field splitting, ZFS) have possible applications in the field of magnetic materials, including single molecule magnets (SMMs). Previous studies have explored the role of coordination number and geometry in controlling the magnetic anisotropy and SMM behavior of high-spin (S = 3/2) Co(II) complexes. Building upon these efforts, the present work examines the impact of ligand oxidation state and structural distortions on the spin states and ZFS parameters of pentacoordinate Co(II) complexes. The five complexes included in this study (1–5) have the general formula, [Co(TpPh2)(LX,Y)]n+ (X = O, S; Y = N, O; n = 0 or 1), where TpPh2 is the scorpionate ligand hydrotris(3,5-diphenyl-pyrazolyl)borate(1−) and LX,Y are bidentate dioxolene-type ligands that can access multiple oxidation states. The specific LX,Y ligands used herein are 4,6-di-tert-butyl substituted o-aminophenolate and o-aminothiophenolate (1 and 2, respectively), o-iminosemiquinonate and o-semiquinonate radicals (3 and 4, respectively), and o-iminobenzoquinone (5). Each complex exhibits a distorted trigonal bipyramidal geometry, as revealed by single-crystal X-ray diffraction. Direct current (dc) magnetic susceptibility experiments confirmed that the complexes with closed-shell ligands (1, 2, and 5) possess S = 3/2 ground states with negative D-values (easy-axis anisotropy) of −41, −78, and −30 cm–1, respectively. For 3 and 4, antiferromagnetic coupling between the Co(II) center and o-(imino)semiquinonate radical ligand results in S = 1 ground states that likewise exhibit very large and negative anisotropy (−100 \u3e D \u3e −140 cm–1). Notably, ZFS was measured directly for each complex using far-infrared magnetic spectroscopy (FIRMS). In combination with high-frequency and -field electron paramagnetic resonance (HFEPR) studies, these techniques provided precise spin-Hamiltonian parameters for complexes 1, 2, and 5. Multireference ab initio calculations, using the CASSCF/NEVPT2 approach, indicate that the strongly negative anisotropies of these Co(II) complexes arise primarily from distortions in the equatorial plane due to constrictions imposed by the TpPh2 ligand. This effect is further amplified by cobalt(II)-radical exchange interactions in 3 and 4

Measuring Dietary Iron Absorption From Edible Tenebrio molitor and Assessing the Effect of Chitin on Iron Bioavailability: A Stable Iron Isotope Study in Young Women

OBJECTIVES: Iron deficiency is estimated to affect up to 1.5–2 billion people worldwide. Edible insects can be a rich source of iron and may have a smaller environmental food print than other animal source foods. Mealworm (Tenebrio molitor) larvae are recognized as an edible insect, but iron bioavailability in humans has not been investigated. Chitin, a major component of insect biomass, is a known iron binder. Our primary objective was to measure fractional iron absorption (FIA) from T.molitor with and without chitin in young women. Secondly, we aimed to assess the effect of the presence of mealworm biomass on iron absorption from iron present in low-phytate maize porridge. METHODS: Non-anemic females (18–45 years, body weight < 65 kg) were recruited and FIA was measured as erythrocyte incorporation of stable isotopes tracers in red blood cells 14 days after test meal administration. Using a randomized cross over design, three different meals were administered to each subject, consisting of A) a low phytate refined maize porridge with (54)FeSO(4); B) intrinsically labelled ((57)Fe) T.molitor with native chitin and extrinsic (58)FeSO(4); C) intrinsically labelled ((57)Fe) T.molitor with reduced chitin and extrinsic (58)FeSO(4). RESULTS: Median serum ferritin concentration in the participating subjects (n = 21) was 22.7 µg/L. Iron content in T.molitor larvae was FIA from meals B ((58)Fe, 5.28%) and C ((58)Fe, 4.55%) in which mealworm biomass was given in combination with maize porridge did not significantly differ to FIA from maize porridge fed alone (5.84%). In case of intrinsic labelling, FIA from meals B ((57)Fe, 4.11%) and C ((57)Fe, 4.03%) were significantly lower compared to maize meal A (P < 0.001). CONCLUSIONS: FIA from T.molitor was similar to low-phytate containing maize. Presence of mealworm biomass did not enhance or inhibit the FIA of iron present in the maize meal. Furthermore, a chitin reduction process did not show any discernible effect on FIA. T.molitor larvae could be a viable source of iron in the human diet, but iron absorption may be similar to plant-based foods. The study was registered at clinicaltrials.gov as NCT04510831. FUNDING SOURCES: Coop Research Program, World Food System Center, ETH Zurich, Switzerland

Measuring dietary iron absorption from edible tenebrio molitor and assessing the effect of chitin on iron bioavailability ::a stable iron isotope study in young women

OBJECTIVES: Iron deficiency is estimated to affect up to 1.5–2 billion people worldwide. Edible insects can be a rich source of iron and may have a smaller environmental food print than other animal source foods. Mealworm (Tenebrio molitor) larvae are recognized as an edible insect, but iron bioavailability in humans has not been investigated. Chitin, a major component of insect biomass, is a known iron binder. Our primary objective was to measure fractional iron absorption (FIA) from T.molitor with and without chitin in young women. Secondly, we aimed to assess the effect of the presence of mealworm biomass on iron absorption from iron present in low-phytate maize porridge. METHODS: Non-anemic females (18–45 years, body weight < 65 kg) were recruited and FIA was measured as erythrocyte incorporation of stable isotopes tracers in red blood cells 14 days after test meal administration. Using a randomized cross over design, three different meals were administered to each subject, consisting of A) a low phytate refined maize porridge with (54)FeSO(4); B) intrinsically labelled ((57)Fe) T.molitor with native chitin and extrinsic (58)FeSO(4); C) intrinsically labelled ((57)Fe) T.molitor with reduced chitin and extrinsic (58)FeSO(4). RESULTS: Median serum ferritin concentration in the participating subjects (n = 21) was 22.7 µg/L. Iron content in T.molitor larvae was FIA from meals B ((58)Fe, 5.28%) and C ((58)Fe, 4.55%) in which mealworm biomass was given in combination with maize porridge did not significantly differ to FIA from maize porridge fed alone (5.84%). In case of intrinsic labelling, FIA from meals B ((57)Fe, 4.11%) and C ((57)Fe, 4.03%) were significantly lower compared to maize meal A (P < 0.001). CONCLUSIONS: FIA from T.molitor was similar to low-phytate containing maize. Presence of mealworm biomass did not enhance or inhibit the FIA of iron present in the maize meal. Furthermore, a chitin reduction process did not show any discernible effect on FIA. T.molitor larvae could be a viable source of iron in the human diet, but iron absorption may be similar to plant-based foods. The study was registered at clinicaltrials.gov as NCT04510831. FUNDING SOURCES: Coop Research Program, World Food System Center, ETH Zurich, Switzerland

The effect of dechitinization on iron absorption from mealworm larvae (Tenebrio molitor) flour added to maize meals ::stable-isotope studies in young females with low iron stores

Edible insects have a low ecological footprint and could serve as an alternative dietary iron source. However, chitin, a major component of insects, avidly binds iron and might inhibit iron absorption. We aimed to measure fractional iron absorption (FIA) from Tenebrio molitor–based test meals with and without dechitinization, and to assess the effect of native and low chitin T. molitor on FIA from iron-fortified maize porridge. We measured iron absorption in young females with low iron stores (n = 21) from 1) labeled (54FeSO4) fortified maize porridge (maize alone); 2) intrinsically labeled (57Fe added during rearing) T. molitor larvae with native chitin content (NC) added to maize alone; and 3) dechitinized intrinsically labeled (57Fe) T. molitor larvae with low chitin content (LC) added to maize alone. We determined FIA using erythrocyte isotope incorporation and measured in vitro iron dialyzability from the 3 meals. NC and LC T. molitor had similar mean ± SD iron content (12.0 ± 0.1 mg/100 g). Geometric mean (95% CI) FIAs from the 3 test meals were 1) maize alone: 5.8% (3.2%, 10.8%); 2) maize + NC T. molitor: 5.3% (2.5%, 11.3%) and 4.1% (1.9%, 8.7%); and 3) maize + LC T. molitor: 4.6% (2.0%, 10.3%) and 4.0% (1.8%, 9.2%), for extrinsic and intrinsic labels, respectively. FIA from NC and LC T. molitor did not significantly differ, and both were lower (P < 0.005) than FIA from the labeled maize porridge in the 3 meals, which did not significantly differ. The slopes of the relations between FIA and serum ferritin in the different meals and from the intrinsic and extrinsic labels did not significantly differ. T. molitor biomass does not strongly affect iron absorption when added to maize porridge. Our data suggest T. molitor iron is absorbed from the common nonheme iron pool. Native T. molitor is high in iron which is moderately well absorbed, suggesting it could be a valuable dietary iron source

Modulation of Prostanoids Profile and Counter-Regulation of SDF-1α/CXCR4 and VIP/VPAC2 Expression by Sitagliptin in Non-Diabetic Rat Model of Hepatic Ischemia-Reperfusion Injury

Molecular mechanisms underlying the beneficial effect of sitagliptin repurposed for hepatic ischemia-reperfusion injury (IRI) are poorly understood. We aimed to evaluate the impact of IRI and sitagliptin on the hepatic profile of eicosanoids (LC-MS/MS) and expression/concentration (RTqPCR/ELISA) of GLP-1/GLP-1R, SDF-1α/CXCR4 and VIP/VPAC1, VPAC2, and PAC1 in 36 rats. Animals were divided into four groups and subjected to ischemia (60 min) and reperfusion (24 h) with or without pretreatment with sitagliptin (5 mg/kg) (IR and SIR) or sham-operated with or without sitagliptin pretreatment (controls and sitagliptin). PGI2, PGE2, and 13,14-dihydro-PGE1 were significantly upregulated in IR but not SIR, while sitagliptin upregulated PGD2 and 15-deoxy-12,14-PGJ2. IR and sitagliptin non-significantly upregulated GLP-1 while Glp1r expression was borderline detectable. VIP concentration and Vpac2 expression were downregulated in IR but not SIR, while Vpac1 was significantly downregulated solely in SIR. IRI upregulated both CXCR4 expression and concentration, and sitagliptin pretreatment abrogated receptor overexpression and downregulated Sdf1. In conclusion, hepatic IRI is accompanied by an elevation in proinflammatory prostanoids and overexpression of CXCR4, combined with downregulation of VIP/VPAC2. Beneficial effects of sitagliptin during hepatic IRI might be mediated by drug-induced normalization of proinflammatory prostanoids and upregulation of PGD2 and by concomitant downregulation of SDF-1α/CXCR4 and reinstating VIP/VCAP2 signaling

GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance

The high neuroactive potential of metabolites produced by gut microbes has gained traction over the last few years, with metagenomic-based studies suggesting an important role of microbiota-derived γ-aminobutyric acid (GABA) in modulating mental health. Emerging evidence has revealed the presence of the glutamate decarboxylase (GAD)-encoding gene, a key enzyme to produce GABA, in the prominent human intestinal genus Bacteroides. Here, we investigated GABA production by Bacteroides in culture and metabolic assays combined with comparative genomics and phylogenetics. A total of 961 Bacteroides genomes were analyzed in silico and 17 metabolically and genetically diverse human intestinal isolates representing 11 species were screened in vitro. Using the model organism Bacteroides thetaiotaomicron DSM 2079, we determined GABA production kinetics, its impact on milieu pH, and we assessed its role in mitigating acid-induced cellular damage. We showed that the GAD-system consists of at least four highly conserved genes encoding a GAD, a glutaminase, a glutamate/GABA antiporter, and a potassium channel. We demonstrated a high prevalence of the GAD-system among Bacteroides with 90% of all Bacteroides genomes (96% in human gut isolates only) harboring all genes of the GAD-system and 16 intestinal Bacteroides strains producing GABA in vitro (ranging from 0.09 to 60.84 mM). We identified glutamate and glutamine as precursors of GABA production, showed that the production is regulated by pH, and that the GAD-system acts as a protective mechanism against acid stress in Bacteroides, mitigating cell death and preserving metabolic activity. Our data also indicate that the GAD-system might represent the only amino acid-dependent acid tolerance system in Bacteroides. Altogether, our results suggest an important contribution of Bacteroides in the regulation of the GABAergic system in the human gut

GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance

The high neuroactive potential of metabolites produced by gut microbes has gained traction over the last few years, with metagenomic-based studies suggesting an important role of microbiota-derived γ-aminobutyric acid (GABA) in modulating mental health. Emerging evidence has revealed the presence of the glutamate decarboxylase (GAD)-encoding gene, a key enzyme to produce GABA, in the prominent human intestinal genus Bacteroides. Here, we investigated GABA production by Bacteroides in culture and metabolic assays combined with comparative genomics and phylogenetics. A total of 961 Bacteroides genomes were analyzed in silico and 17 metabolically and genetically diverse human intestinal isolates representing 11 species were screened in vitro. Using the model organism Bacteroides thetaiotaomicron DSM 2079, we determined GABA production kinetics, its impact on milieu pH, and we assessed its role in mitigating acid-induced cellular damage. We showed that the GAD-system consists of at least four highly conserved genes encoding a GAD, a glutaminase, a glutamate/GABA antiporter, and a potassium channel. We demonstrated a high prevalence of the GAD-system among Bacteroides with 90% of all Bacteroides genomes (96% in human gut isolates only) harboring all genes of the GAD-system and 16 intestinal Bacteroides strains producing GABA in vitro (ranging from 0.09 to 60.84 mM). We identified glutamate and glutamine as precursors of GABA production, showed that the production is regulated by pH, and that the GAD-system acts as a protective mechanism against acid stress in Bacteroides, mitigating cell death and preserving metabolic activity. Our data also indicate that the GAD-system might represent the only amino acid-dependent acid tolerance system in Bacteroides. Altogether, our results suggest an important contribution of Bacteroides in the regulation of the GABAergic system in the human gut

<i>Cornus mas</i> L. Extract Targets the Specific Molecules of the Th17/Treg Developmental Pathway in TNBS-Induced Experimental Colitis in Rats

Given that one of the crucial events in the pathogenesis of inflammatory bowel disease is the loss of homeostasis between Th17 and Treg cells, targeting the specific molecules of the Th17/Treg axis developmental pathway is a promising strategy for inflammatory bowel disease prevention and treatment. The current study aimed to assess the impact of cornelian cherry (Cornus mas L.) extract, rich in iridoids and polyphenols known for their potential anti-inflammatory activity, at two doses (20 or 100 mg/kg) on the crucial factors for Th17/Treg cell differentiation in the course of experimental colitis and compare this action with that of sulfasalazine. This study was conducted on the biobank colon tissue samples collected during the previous original experiment, in which colitis in rats was induced by trinitrobenzenesulfonic acid (TNBS). The levels of IL-6, RORγt, total STAT3, p-STAT3, and Foxp3 were determined by ELISA. The expression of PIAS3 mRNA was quantified by qPCR. Cornelian cherry extract at a dose of 100 mg/kg counteracted the TNBS-induced elevation of IL-6, RORγt, and p-STAT3 levels and a decrease in Foxp3 level and PIAS3 mRNA expression, while given concomitantly with sulfasalazine was more effective than sulfasalazine alone in reversing the TNBS-induced changes in IL-6, RORγt, total STAT3, p-STAT3, Foxp3 levels, and PIAS3 mRNA expression. The beneficial effect of cornelian cherry extract on experimental colitis may be due to its immunomodulatory activity reflected by the influence on factors regulating the Th17/Treg axis

The main determinants of iodine in cows’ milk in Switzerland are farm type, season and teat dipping

ISSN:0007-1145ISSN:1475-266