A Gadolinium(III) Complex Based on Pyridoxine Molecule with Single-Ion Magnet and Magnetic Resonance Imaging Properties.

Pyridoxine (pyr) is a versatile molecule that forms part of the family of B vitamins. It is used to treat and prevent vitamin B6 deficiency and certain types of metabolic disorders. Moreover, the pyridoxine molecule has been investigated as a suitable ligand toward metal ions. Nevertheless, the study of the magnetic properties of metal complexes containing lanthanide(III) ions and this biomolecule is unexplored. We have synthesized and characterized a novel pyridoxine-based GdIII complex of formula [GdIII(pyr)2(H2O)4]Cl3 · 2 H2O (1) [pyr = pyridoxine]. 1 crystallizes in the triclinic system and space group Pi. In its crystal packing, cationic [Gd(pyr)2(H2O)4]3+ entities are connected through H-bonding interactions involving non-coordinating water molecules and chloride anions. In addition, Hirshfeld surfaces of 1 were calculated to further investigate their intermolecular interactions in the crystal lattice. Our investigation of the magnetic properties of 1, through ac magnetic susceptibility measurements, reveals the occurrence of a slow relaxation in magnetization in this mononuclear GdIII complex, indicating an unusual single-ion magnet (SIM) behavior for this pseudo-isotropic metal ion at very low temperatures. We also studied the relaxometric properties of 1, as a potential contrast agent for high-field magnetic resonance imaging (MRI), from solutions of 1 prepared in physiological serum (0.0-3.2 mM range) and measured at 3 T on a clinical MRI scanner. The values of relaxivity obtained for 1 are larger than those of some commercial MRI contrast agents based on mononuclear GdIII systems.

Lacticaseibacillus rhamnosus ATCC 53103 and Limosilactobacillus reuteri ATCC 53608 Synergistically Boost Butyrate Levels upon Tributyrin Administration Ex Vivo.

Modulation of the gut microbiota is a trending strategy to improve health. While butyrate has been identified as a key health-related microbial metabolite, managing its supply to the host remains challenging. Therefore, this study investigated the potential to manage butyrate supply via tributyrin oil supplementation (TB; glycerol with three butyrate molecules) using the ex vivo SIFR® (Systemic Intestinal Fermentation Research) technology, a highly reproducible, in vivo predictive gut model that accurately preserves in vivo-derived microbiota and enables addressing interpersonal differences. Dosing 1 g TB/L significantly increased butyrate with 4.1 (±0.3) mM, corresponding with 83 ± 6% of the theoretical butyrate content of TB. Interestingly, co-administration of Limosilactobacillus reuteri ATCC 53608 (REU) and Lacticaseibacillus rhamnosus ATCC 53103 (LGG) markedly enhanced butyrate to levels that exceeded the theoretical butyrate content of TB (138 ± 11% for REU; 126 ± 8% for LGG). Both TB + REU and TB + LGG stimulated Coprococcus catus, a lactate-utilizing, butyrate-producing species. The stimulation of C. catus with TB + REU was remarkably consistent across the six human adults tested. It is hypothesized that LGG and REU ferment the glycerol backbone of TB to produce lactate, a precursor of butyrate. TB + REU also significantly stimulated the butyrate-producing Eubacterium rectale and Gemmiger formicilis and promoted microbial diversity. The more potent effects of REU could be due to its ability to convert glycerol to reuterin, an antimicrobial compound. Overall, both the direct butyrate release from TB and the additional butyrate production via REU/LGG-mediated cross-feeding were highly consistent. This contrasts with the large interpersonal differences in butyrate production that are often observed upon prebiotic treatment. Combining TB with LGG and especially REU is thus a promising strategy to consistently supply butyrate to the host, potentially resulting in more predictable health benefits.

Lipoic Acid-Functionalized Hexanuclear Manganese(III) Nanomagnets Suitable for Surface Grafting.

Highly anisotropic single-molecule magnets (SMMs) have attracted much interest in the field of molecular magnetism because of their spin features and potential technological applications. Additionally, a great effort has been devoted to the functionalization of such molecule-based systems which are made with ligands containing functional groups suitable to connect SMMs to junction devices or to perform their grafting on surfaces of different substrates. We have synthesized and characterized two lipoic acid-functionalized and oxime-based Mn(III) compounds, of formula [Mn6(µ3-O)2(H2N-sao)6(lip)2(MeOH)6][Mn6(µ3-O)2(H2N-sao)6(cnph)2(MeOH)6]}·10MeOH (1) and [Mn6(µ3-O)2(H2N-sao)6(lip)2(EtOH)6]·EtOH·2H2O (2) [H2N-saoH2 = salicylamidoxime, lip = lipoate anion, cnph = 2-cyanophenolate anion]. Compound 1 crystallizes in the space group Pi of the triclinic system and 2 crystallizes in the space group C2/c of the monoclinic system. In the crystal, neighboring Mn6 entities are linked using non-coordinating solvent molecules, which are H-bonded to N atoms of -NH2 groups of amidoxime ligand. In addition, Hirshfeld surfaces of 1 and 2 were calculated to study the variety of intermolecular interactions and the different levels of importance that take place in their crystal lattice; this type of computed study is the first time performed on Mn6 complexes. The study of the magnetic properties of 1 and 2 through dc magnetic susceptibility measurements reveals the coexistence of ferromagnetic and antiferromagnetic exchange couplings between the Mn(III) metal ions in both compounds, the latter being the predominant magnetic interaction. A spin S = 4 value of the ground state was obtained using isotropic simulations of the experimental magnetic susceptibility data for both 1 and 2. Ac magnetic susceptibility measurements show features typical of slow relaxation of the magnetization in 1 and 2, which indicate that SMM behavior takes place in both compounds.

Enantiomeric Complexes Based on Ruthenium(III) and 2,2'-Biimidazole: X-ray Structure and Magnetic Properties.

We have prepared and characterized two Ru(III) compounds based on the 2,2'-biimidazole (H2biim) ligand, namely, a single complex of formula cis-[RuCl2(H2biim)2]Cl·4H2O (1) and a racemic mixture of formula {cis-[RuCl2(H2biim)2]Cl}2·4H2O (2), which contains 50% of Ru(III) complex 1. Both compounds crystallize in the monoclinic system with space groups C2 and P21 for 1 and 2, respectively. These complexes exhibit the metal ion bonded to four nitrogen atoms from two H2biim molecules and two chloride ions, which balance part of the positive charges in a distorted octahedral geometry. Significant differences are observed in their crystal packing, which leads to the observation of differences in their respective magnetic behaviors. Despite having imidazole rings in both compounds, π-π stacking interactions occur only in the crystal structure of 2, and the shortest intermolecular Ru···Ru separation in 2 is consequently shorter than that in 1. Variable-temperature dc magnetic susceptibility measurements performed on polycrystalline samples of 1 and 2 reveal different magnetic behaviors at low temperatures: while 1 behaves pretty much as a magnetically isolated mononuclear Ru(III) complex with S = 1/2, 2 exhibits the behavior of an antiferromagnetically coupled system with S = 0 and a maximum in the magnetic susceptibility curve at approximately 3.0 K.

Age-Dependent Prebiotic Effects of Soluble Corn Fiber in M-SHIME® Gut Microbial Ecosystems.

Soluble corn fiber (SCF) has demonstrated prebiotic effects in clinical studies. Using an in vitro mucosal simulator of the human intestinal microbial ecosystem (M-SHIME®) model, the effects of SCF treatment on colonic microbiota composition and metabolic activity and on host-microbiome interactions were evaluated using fecal samples from healthy donors of different ages (baby [≤ 2 years], n = 4; adult [18-45 years], n = 2; elderly [70 years], n = 1). During the 3-week treatment period, M-SHIME® systems were supplemented with SCF daily (baby, 1.5, 3, or 4.5 g/d; adult, 3 or 8.5 g/d; and elderly, 8.5 g/d). M-SHIME® supernatants were evaluated for their effect on the intestinal epithelial cell barrier and inflammatory responses in lipopolysaccharide. (LPS)-stimulated cells. Additionally, short-chain fatty acid (SCFA) production and microbial community composition were assessed. In the baby and adult models, M-SHIME® supernatants from SCF treated vessels protected Caco-2 membrane integrity from LPS-induced damage. SCF treatment resulted in the expansion of Bacteroidetes, Firmicutes, and Bifidobacterial, as well as increased SCFA production in all age groups. SCF tended to have the greatest effect on propionate production. These findings demonstrate the prebiotic potential of SCF in babies, adults, and the elderly and provide insight into the mechanisms behind the observed prebiotic effects.

Versatile human in vitro triple coculture model coincubated with adhered gut microbes reproducibly mimics pro-inflammatory host-microbe interactions in the colon.

The colonic epithelial barrier is vital to preserve gut and host health by maintaining the immune homeostasis between host and microbes. The mechanisms underlying beneficial or harmful host-microbe interactions are poorly understood and impossible to study in vivo given the limited accessibility and ethical constraints. Moreover, existing in vitro models lack the required cellular complexity for the routine, yet profound, analysis of the intricate interplay between different types of host and microbial cells. We developed and characterized a broadly applicable, easy-to-handle in vitro triple coculture model that combines chemically-induced macrophage-like, goblet and epithelial cells covered by a mucus layer, which can be coincubated with complex human-derived gut microbiota samples for 16 h. Comparison with a standard epithelial monolayer model revealed that triple cocultures produce thicker mucus layers, morphologically organize in a network and upon exposure to human-derived gut microbiota samples, respond via pro-inflammatory cytokine production. Both model systems, however, were not suffering from cytotoxic stress or different microbial loads, indicating that the obtained endpoints were caused by the imposed conditions. Addition of the probiotic Lactobacillus rhamnosus GG to assess its immunomodulating capacity in the triple coculture slightly suppressed pro-inflammatory cytokine responses, based on transcriptomic microarray analyses. TNF conditioning of the models prior to microbial exposure did not cause shifts in cytokines, suggesting a strong epithelial barrier in which TNF did not reach the basolateral side. To conclude, the triple coculture model is tolerable towards manipulations and allows to address mechanistic host-microbe research questions in a stable in vitro environment.

A Gadolinium(III) Complex Based on the Thymine Nucleobase with Properties Suitable for Magnetic Resonance Imaging.

The paramagnetic gadolinium(III) ion is used as contrast agent in magnetic resonance (MR) imaging to improve the lesion detection and characterization. It generates a signal by changing the relaxivity of protons from associated water molecules and creates a clearer physical distinction between the molecule and the surrounding tissues. New gadolinium-based contrast agents displaying larger relaxivity values and specifically targeted might provide higher resolution and better functional images. We have synthesized the gadolinium(III) complex of formula [Gd(thy)2(H2O)6](ClO4)3·2H2O (1) [thy = 5-methyl-1H-pyrimidine-2,4-dione or thymine], which is the first reported compound based on gadolinium and thymine nucleobase. 1 has been characterized through UV-vis, IR, SEM-EDAX, and single-crystal X-ray diffraction techniques, and its magnetic and relaxometric properties have been investigated by means of SQUID magnetometer and MR imaging phantom studies, respectively. On the basis of its high relaxivity values, this gadolinium(III) complex can be considered a suitable candidate for contrast-enhanced magnetic resonance imaging.

Ferro- and Antiferromagnetic Interactions in Oxalato-Centered Inverse Hexanuclear and Chain Copper(II) Complexes with Pyrazole Derivatives.

Two novel copper(II) complexes of formulas {[Cu(4-Hmpz)4][Cu(4-Hmpz)2(µ3-ox-κ2O1,O2:κO2':κO1')(ClO4)2]}n (1) and {[Cu(3,4,5-Htmpz)4]2[Cu(3,4,5-Htmpz)2(µ3-ox-κ2O1,O2:κO2':κO1')(H2O)(ClO4)]2[Cu2(3,4,5-Htmpz)4(µ-ox-κ2O1,O2:κ2O2',O1')]}(ClO4)4·6H2O (2) have been obtained by using 4-methyl-1H-pyrazole (4-Hmpz) and 3,4,5-trimethyl-1H-pyrazole (3,4,5-Htmpz) as terminal ligands and oxalate (ox) as the polyatomic inverse coordination center. The crystal structure of 1 consists of perchlorate counteranions and cationic copper(II) chains with alternating bis(pyrazole)(µ3-κ2O1,O2:κO2':κO1'-oxalato)copper(II) and tetrakis(pyrazole)copper(II) fragments. The crystal structure of 2 is made up of perchlorate counteranions and cationic centrosymmetric hexanuclear complexes where an inner tetrakis(pyrazole)(µ-κ2O1,O2:κ2O2',O1'-oxalato)dicopper(II) entity and two outer mononuclear tetrakis(pyrazole)copper(II) units are linked through two mononuclear aquabis(pyrazole)(µ3-κ2O1,O2:κO2':κO1'-oxalato)copper(II) units. The magnetic properties of 1 and 2 were investigated in the temperature range 2.0-300 K. Very weak intrachain antiferromagnetic interactions between the copper(II) ions through the µ3-ox-κ2O1,O2:κO2':κO1' center occur in 1 [J = -0.42(1) cm-1, the spin Hamiltonian being defined as H = -J∑S1,i · S2,i+1], whereas very weak intramolecular ferromagnetic [J = +0.28(2) cm-1] and strong antiferromagnetic [J' = -348(2) cm-1] couplings coexist in 2 which are mediated by the µ3-ox-κ2O1,O2:κO2':κO1' and µ-ox-κ2O1,O2:κ2O2',O1' centers, respectively. The variation in the nature and magnitude of the magnetic coupling for this pair of oxalato-centered inverse copper(II) complexes is discussed in the light of their different structural features, and a comparison with related oxalato-centered inverse copper(II)-pyrazole systems from the literature is carried out.

Supplementation of a propionate-producing consortium improves markers of insulin resistance in an in vitro model of gut-liver axis.

Gut-liver cross talk is an important determinant of human health with profound effects on energy homeostasis. While gut microbes produce a huge range of metabolites, specific compounds such as short-chain fatty acids (SCFAs) can enter the portal circulation and reach the liver (Brandl K, Schnabl B. Curr Opin Gastroenterol 33: 128-133, 2017), a central organ involved in glucose homeostasis and diabetes control. Propionate is a major SCFA involved in activation of intestinal gluconeogenesis (IGN), thereby regulating food intake, enhancing insulin sensitivity, and leading to metabolic homeostasis. Although microbiome-modulating strategies may target the increased microbial production of propionate, it is not clear whether such an effect spreads through to the hepatic cellular level. Here, we designed a propionate-producing consortium using a selection of commensal gut bacteria, and we investigated how their delivered metabolites impact an in vitro enterohepatic model of insulin resistance. Glycogen storage on hepatocyte-like cells and inflammatory markers associated with insulin resistance were evaluated to understand the role of gut metabolites on gut-liver cross talk in a simulated scenario of insulin resistance. The metabolites produced by our consortium increased glycogen synthesis by ~57% and decreased proinflammatory markers such as IL-8 by 12%, thus elucidating the positive effect of our consortium on metabolic function and low-grade inflammation. Our results suggest that microbiota-derived products can be a promising multipurpose strategy to modulate energy homeostasis, with the potential ability to assist in managing metabolic diseases due to their adaptability.

Pyrazolylamidino ligands from coupling of acetonitrile and pyrazoles: a systematic study.

Mixed pyrazole-acetonitrile complexes, both neutral fac-[ReBr(CO)3(NCMe)(pz*H)] (pz*H = pzH, pyrazole; dmpzH, 3,5-dimethylpyrazole; or indzH, indazole) and cationic fac-[Re(CO)3(NCMe)(pz*H)2]A (A = BF4, ClO4, or OTf), are described. Their role as the only starting products to obtain final pyrazolylamidino complexes fac-[ReBr(CO)3(NH═C(Me)pz*-κ(2)N,N)] and fac-[Re(CO)3(pz*H)(NH═C(Me)pz*-κ(2)N,N)]A, respectively, is examined. Other products involved in the processes, such as fac-[ReBr(CO)3(pz*H)2], fac-[Re(CO)3(NCMe)(NH═C(Me)pz*-κ(2)N,N)]A, and fac-[Re(CO)3(pz*H)2(OTf)] are also described. Warming CD3CN solutions of fac-[Re(CO)3(NCMe)(pz*H)2]A at 40 °C gives cleanly the pyrazolylamidino complexes [Re(CO)3(pz*H)(NH═C(Me)pz*-κ(2)N,N)]A as the only products, pointing to an intramolecular process. This is confirmed by carrying out reactions in the presence of one equivalent of a pyrazole different from that coordinated, which affords complexes where the pyrazolylamidino ligand contains only the pyrazole previously coordinated. When the reactions lead to an equilibrium mixture of the final and starting products, the reverse reaction gives the same equilibrium mixture, which indicates that the coupling reaction of pyrazoles and nitriles to obtain pyrazolylamidino ligands is a reversible intramolecular process. A systematic study of the possible factors which may affect the reaction gives the following results: (a) the yields of the direct reactions are higher for lower temperatures; (b) the tendency of the pyrazoles to give pyrazolylamidino complexes follows the sequence indzH > pzH > dmpzH; and (c) the reaction rates do not depend on the nature of the anion even when a large excess is added. The presence of a small amount of aqueous solution of NaOH catalyzes the reaction. Thus, addition of 0.5-1% of NaOH (aq) to solutions of fac-[ReBr(CO)3(NCMe)(pz*H)] (in CD3CN) or fac-[Re(CO)3(NCMe)(pz*H)2]A (in CD3CN, CD3NO2 or (CD3)2CO) allowed the syntheses of the corresponding pyrazolylamidino complexes [ReBr(CO)3(NH═C(Me)pz*-κ(2)N,N)] or [Re(CO)3(pz*H)(NH═C(Me)pz*-κ(2)N,N)]A with better yields, more rapidly, and in milder conditions.

The Effect of a Program to Improve Adherence to the Mediterranean Diet on Cardiometabolic Parameters in 7034 Spanish Workers.

BACKGROUND: Cardiovascular and metabolic diseases include a large group of pathologies and constitute one of the most serious chronic health problems facing the 21st century, with high rates of morbidity and mortality worldwide. Unhealthy diets influence the development of these pathologies. The Mediterranean diet can be an important part in the treatment of these diseases. The objective of this study was to assess the effect of a program that aims to increase adherence to the Mediterranean diet on the improvement of different cardiometabolic risk parameters. METHODS: A prospective intervention study was carried out on 7034 Spanish workers. Prior to the intervention, 22 cardiometabolic risk scales were evaluated. Participants in this study were informed both orally and in writing of the characteristics and benefits of the Mediterranean diet and were given the website of the Ministry of Health, Consumption and Social Welfare of Spain, which provides advice on nutrition. Adherence to the Mediterranean diet was reinforced by sending a monthly SMS to their mobile phones. After six months of follow-up, the 22 risk scales were re-evaluated to assess changes. Means and standard deviations were calculated using Student's t test to analyse quantitative variables. Prevalence was calculated using the Chi-square test when the variables were qualitative. RESULTS: All the cardiometabolic risk scales studied decreased after implementing a program to improve and enhance adherence to the Mediterranean diet. The number of losses in the sample was very low, standing at 4.31%. CONCLUSIONS: The Mediterranean diet is effective in reducing all cardiovascular risk scales evaluated. The mean values and prevalence of high values of the different cardiometabolic risk scales analysed led to lower values after the implementation of the program to increase adherence to the Mediterranean diet. We observed a significant positive difference in metabolic age in both sexes. We have obtained a significant improvement in the insulin resistance index, especially in the SPISE-IR index, data that we have not found in previous publications. Easy access to the Internet and new information and communication technologies facilitate adherence to a diet and can reduce the number of losses.

Magnetocaloric efficiency tuning through solvent-triggered 3D to 2D interconversion in holmium(III)-based dynamic MOFs.

The neutral holmium(III) oxalate octadecahydrate {[Ho2(ox)3(H2O)6]·12H2O}n of mixed hexagonal/decagonal (63·103) 3D net topology shows important changes in the magnetocaloric efficiency upon dehydration/rehydration by heating and water vapor exposition to give the holmium(III) oxalate decahydrate {[Ho2(ox)3(H2O)6]·4H2O}n of hexagonal (63) 2D net topology through the intermediacy of the elusive amorphous anhydrous compound {Ho2(ox)3}n.

Pleuropulmonary and diaphragmatic ultrasound in intensive care medicine.

The usefulness of ultrasound for chest exploration was described in 1968. It was not until the 1990s, when its use became widespread in Intensive Care Units as a diagnostic, monitoring and procedural guide tool. The fact that it is a non-invasive tool, accessible at the bedside, with a sensitivity and specificity close to computerized tomography (CT) and with a short learning curve, have made it a mandatory technique in the management of critically ill patients. It is essential to know that there are different air/fluid ratio generated by different pathologies that gives rise to one echographic pattern or another. The identification of these patterns together with the clinical information will allow to make an accurate diagnosis in most settings of respiratory failure. Likewise, we must not forget the importance of evaluating diaphragmatic function by ultrasound during weaning from mechanical ventilation.

ZNF330/NOA36 interacts with HSPA1 and HSPA8 and modulates cell cycle and proliferation in response to heat shock in HEK293 cells.

BACKGROUND: The human genome contains nearly 20.000 protein-coding genes, but there are still more than 6,000 proteins poorly characterized. Among them, ZNF330/NOA36 stand out because it is a highly evolutionarily conserved nucleolar zinc-finger protein found in the genome of ancient animal phyla like sponges or cnidarians, up to humans. Firstly described as a human autoantigen, NOA36 is expressed in all tissues and human cell lines, and it has been related to apoptosis in human cells as well as in muscle morphogenesis and hematopoiesis in Drosophila. Nevertheless, further research is required to better understand the roles of this highly conserved protein. RESULTS: Here, we have investigated possible interactors of human ZNF330/NOA36 through affinity-purification mass spectrometry (AP-MS). Among them, NOA36 interaction with HSPA1 and HSPA8 heat shock proteins was disclosed and further validated by co-immunoprecipitation. Also, "Enhancer of Rudimentary Homolog" (ERH), a protein involved in cell cycle regulation, was detected in the AP-MS approach. Furthermore, we developed a NOA36 knockout cell line using CRISPR/Cas9n in HEK293, and we found that the cell cycle profile was modified, and proliferation decreased after heat shock in the knocked-out cells. These differences were not due to a different expression of the HSPs genes detected in the AP-MS after inducing stress. CONCLUSIONS: Our results indicate that NOA36 is necessary for proliferation recovery in response to thermal stress to achieve a regular cell cycle profile, likely by interaction with HSPA1 and HSPA8. Further studies would be required to disclose the relevance of NOA36-EHR interaction in this context.

Amino Acid Digestibility of Different Formulations of Torula Yeast in an In Vitro Porcine Gastrointestinal Digestion Model and Their Protective Effects on Barrier Function and Inflammation in a Caco-2/THP1Co-Culture Model.

Single-cell protein from torula yeast (Cyberlindnera jadinii) grown on lignocellulosic biomass has been proven to be an excellent alternative protein source for animal feed. This study aimed to evaluate the amino acid (AA) digestibility by estimating intestinal absorption from three yeast-based ingredients, produced by cultivating C. jadinii on hydrolysate, using either mixed woody species (drum- (WDI) or spray-dried (WSI)) or corn dextrose (drum-dried (DDI)) as the carbon source. Further, the protective effect of intestinal digests on activated THP1-Blue™-induced epithelial damage and cytokine profile was evaluated. Total protein content from these three ingredients ranged from 34 to 45%, while the AA dialysis showed an estimated bioaccessibility between 41 and 58%, indicating good digestibility of all test products. A protective effect against epithelial-induced damage was observed for two of the three tested products. Torula yeast cultivated on wood and drum-dried (WDI) and torula yeast cultivated on wood and spray-dried (WSI) significantly increased transepithelial electrical resistance (TEER) values (111-147%, p < 0.05), recovering the epithelial barrier from the inflammation-induced damage in a dose-dependent manner. Further, WSI digests significantly reduced IL8 (250.8 ± 28.1 ng/mL), IL6 (237.9 ± 1.8 pg/mL) and TNF (2797.9 ± 216.3 pg/mL) compared to the blank control (IL8 = 485.7 ± 74.4 ng/mL, IL6 = 478.7 ± 58.9 pg/mL; TNF = 4273.5 ± 20.9 pg/mL) (p < 0.05). These results align with previous in vivo studies, supporting torula yeast-based ingredients as a high-quality protein source for pigs, protecting the intestinal barrier from inflammatory damage, and reducing the pro-inflammatory response. We provided novel insights into the mechanisms behind the health improvement of pigs fed on torula yeast-based ingredients, with potential applications for designing nutritional interventions to recover intestinal homeostasis during critical production periods, such as weaning.

Rare earth elements as statistical sentinels of pollution and paleoenvironments?: Application to a highly polluted estuary in southwestern Spain.

Multivariate analyses have been applied to the REE contents of three cores collected in the Tinto estuary, SW Spain, an extremely polluted area. Results indicate an extremely correlation between all REE, which behave as a single variable. A slight natural pollution peak and three anthropogenic pollution peaks are identified, related with the first mining activities, the Roman period and a recent intensive mining accompanied by a heavy industrial pollution. In all these peaks, the increase of Cu is parallel to that of MREE, which are configured as the best indicators of pollution among REE. Statistical analyses clearly differentiate four groups, each consisting of samples from different environments. Although grain size and this strong pollution alter the study of REE as environmental indicators, it is possible to recognise groups of samples with a common origin or to identify the surface extent of a given pollution peak.

Coordination versus coupling of dicyanamide in molybdenum and manganese pyrazole complexes.

The reactions of cis-[MoCl(η(3)-methallyl)(CO)(2)(NCMe)(2)] (methallyl = CH(2)C(CH(3))CH(2)) with Na(NCNCN) and pz*H (pzH, pyrazole, or dmpzH, 3,5-dimethylpyrazole) lead to cis-[Mo(η(3)-methallyl)(CO)(2)(pz*H)(µ-NCNCN-κ(2)N,N)](2) (pzH, 1a; dmpzH, 1b), where dicyanamide is coordinated as bridging ligand. Similar reactions with fac-[MnBr(CO)(3)(NCMe)(2)] lead to the pyrazolylamidino complexes fac-[Mn(pz*H)(CO)(3)(NH═C(pz*)NCN-κ(2)N,N)] (pzH, 2a; dmpzH, 2b), resulting from the coupling of pyrazol with one of the CN bonds of dicyanamide. The second CN bond of dicyanamide in 2a undergoes a second coupling with pyrazole after addition of 1 equiv of fac-[MnBr(CO)(3)(pzH)(2)], yielding the dinuclear doubly coupled complex [{fac-Mn(pzH)(CO)(3)}(2)(µ-NH═C(pz)NC(pz)=NH-κ(4)N,N,N,N)]Br (3). The crystal structure of 3 reveals the presence of two isomers, cis or trans, depending on whether the terminal pyrazoles are coordinated at the same or at different sides of the approximate plane defined by the bridging bis-amidine ligand. Only the cis isomer is detected in the crystal structure of the perchlorate salt of the same bimetallic cation (4), obtained by metathesis with AgClO(4). All the N-bound hydrogen atoms of the cations in 3 or 4 are involved in hydrogen bonds. Some of the C-N bonds of the pyrazolylamidino ligand have a character intermediate between single and double, and theoretical studies were carried out on 2a and 3 to confirm its electronic origin and discard packing effects. Calculations also show the essential role of bromide in the planarity of the tetradentate ligand in the bimetallic complex 3.

In vitro triple coculture with gut microbiota from spondyloarthritis patients is characterized by inter-individual differences in inflammatory responses.

Spondyloarthritis is a group of chronic inflammatory diseases that primarily affects axial or peripheral joints and is frequently associated with inflammation at non-articular sites. The disease is multifactorial, involving genetics, immunity and environmental factors, including the gut microbiota. In vivo, microbiome contributions are difficult to assess due to the multifactorial disease complexity. In a proof-of-concept approach, we therefore used a triple coculture model of immune-like, goblet and epithelial cells to investigate whether we could detect a differential impact from spondyloarthritis- vs. healthy-derived gut microbiota on host cell response. Despite their phylogenetic resemblance, flow cytometry-based phenotypic clustering revealed human-derived gut microbiota from healthy origin to cluster together and apart from spondyloarthritis donors. At host level, mucus production was higher upon exposure to healthy microbiota. Pro-inflammatory cytokine responses displayed more inter-individual variability in spondyloarthritis than in healthy donors. Interestingly, the high dominance in the initial sample of one patient of Prevotella, a genus previously linked to spondyloarthritis, resulted in the most differential host response upon 16 h host-microbe coincubation. While future research should further focus on inter-individual variability by using gut microbiota from a large cohort of patients, this study underscores the importance of the gut microbiota during the SpA disease course.

A novel adenine-based diruthenium(III) complex: Synthesis, crystal structure, electrochemical properties and evaluation of the anticancer activity.

Metal complexes based on purine nucleobases can be a very useful tool in the diagnosis and treatment of some diseases as well as in other biomedical applications. We have prepared and characterized a novel dinuclear ruthenium(III) complex based on the nucleobase adenine of formula [{Ru(µ-Cl)(µ-Hade)}2Cl4]Cl2·2H2O (1) [Hade = protonated adenine]. Complex 1 was characterized through Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDX), magnetometer (SQUID) and cyclic voltammetry (CV) techniques. The crystal structure of 1 was determined by single-crystal X-ray diffraction. 1 crystallizes in the monoclinic system with space group P21/n. Each ruthenium(III) ion is six-coordinate and bonded to four Cl atoms [the average value of the RuIII-Cl bonds lengths is ca. 2.329(1) Å] and two N atoms (N3 and N9) from two adenine molecules, the N1 atom being protonated in both of them. The anticancer activity was evaluated through cell viability assays performed on a colon cancer (HCT116) and a gastric cancer cell lines (AGS), 1 showing an incipient anticancer effect on the AGS cell line at the highest concentration used in the study.

RUNAT-BI: A Ruthenium(III) Complex as a Selective Anti-Tumor Drug Candidate against Highly Aggressive Cancer Cell Lines.

Ruthenium compounds have demonstrated promising activity in different cancer types, overcoming several limitations of platinum-based drugs, yet their global structure-activity is still under debate. We analyzed the activity of Runat-BI, a racemic Ru(III) compound, and of one of its isomers in eight tumor cell lines of breast, colon and gastric cancer as well as in a non-tumoral control. Runat-BI was prepared with 2,2'-biimidazole and dissolved in polyethylene glycol. We performed assays of time- and dose-dependent viability, migration, proliferation, and expression of pro- and antiapoptotic genes. Moreover, we studied the growth rate and cell doubling time to correlate it with the apoptotic effect of Runat-BI. As a racemic mixture, Runat-BI caused a significant reduction in the viability and migration of three cancer cell lines from colon, gastric and breast cancer, all of which displayed fast proliferation rates. This compound also demonstrated selectivity between tumor and non-tumor lines and increased proapoptotic gene expression. However, the isolated isomer did not show any effect. Racemic Runat-BI is a potential drug candidate for treatment of highly aggressive tumors. Further studies should be addressed at evaluating the role of the other isomer, for a more precise understanding of its antitumoral potential and mechanism of action.