Raman spectroscopy and molecular dynamics simulations of aqueous two-phase systems for the purification of phosphoric acid.

In this work, Raman spectroscopy and molecular dynamics simulations were used to elucidate key interactions between polyethylene glycol (PEG) and phosphoric acid (H3PO4) in aqueous two-phase systems for the extraction of phosphoric acid. Extensive molecular dynamics simulations were performed, and radial distribution functions as well as hydrogen bonds between PEG and other molecules were measured. Experimental data were used in combination with the slope method to infer PEG-H3PO4 interactions, and the interpretation is consistent with molecular simulation results. Based on our experimental and simulation results, we propose a solvation mechanism governed by hydrogen bonding interactions: at low concentrations of H3PO4 within the polymer-rich aqueous solution, entropy dominates and phosphoric acid molecules have weak interactions with PEG; as the concentration of phosphoric acid increases above a certain critical value, enthalpy dominates with PEG molecules interacting strongly with H3PO4 molecules via hydrogen bonds.

Fenotipos de la enfermedad por reflujo gastroesofágico: una visión basada en su fisiopatología.

The advancement of knowledge in pathophysiology and underlying etiologies of gastroesophageal reflux disease (GERD) has allowed the development of the concept of disease beyond the acidity of reflux. The variability in the symptom presentation and the response to treatment cannot be attributed only to reflux composition, since esophageal factors, such as structural, mechanical, biochemical, and physiological aspects, play an important role. The proposed personalized approach to GERD uses a stepwise approach that optimizes performance and phenotypic outcome while minimizing invasiveness, risk, and cost. Throughout the staggered approach to determine the GERD phenotype, clinicians may choose to stop further testing and continue treatment if available information identifies a different GERD phenotype. Since not all phenotypes GERD are the same and not all treatments are appropriate for all patients, therapeutic strategies must be personalized according to their phenotype.

El avance del conocimiento sobre la fisiopatología y la etiología subyacentes a la enfermedad por reflujo gastroesofágico (ERGE) ha permitido que el desarrollo de esta se extienda más allá de la acidez del reflujo. La variabilidad en la presentación de los síntomas y la respuesta al tratamiento no se puede atribuir solo a la composición del reflujo, ya que factores esofágicos, como aspectos estructurales, mecánicos, bioquímicos y fisiológicos, desempeñan un papel importante. El enfoque personalizado propuesto para la ERGE utiliza un método gradual que optimiza el rendimiento y el resultado fenotípico, y minimiza la invasividad, el riesgo y el costo. A lo largo del método escalonado para determinar el fenotipo de la ERGE, los médicos pueden optar por detener las pruebas adicionales y continuar con el tratamiento si la información disponible identifica un fenotipo de ERGE distinto. Dado que la ERGE no es la misma y no todos los tratamientos disponibles para controlarla son apropiados para todos los pacientes, las estrategias terapéuticas deben personalizarse de acuerdo con su fenotipo.

Curvature and confinement effects on chiral liquid crystal morphologies.

Chiral liquid crystals (ChLCs) exhibit an inherent twist that originates at the molecular scale and can extend over multiple length scales when unconstrained. Under confinement, the twist is thwarted, leading to formation of defects in the molecular order that offer distinct optical responses and opportunities for colloidal driven assembly. Past studies have explored spheroidal confinement down to the nanoscopic regime, where curved boundaries produce surface defects to accommodate topological constraints and restrict the propagation of cuboidal defect networks. Similarly, strict confinement in channels and shells has been shown to give rise to escaped configurations and skyrmions. However, little is known about the role of extrinsic curvature in the development of cholesteric textures and Blue Phases (BP). In this paper, we examine the palette of morphologies that arises when ChLCs are confined in toroidal and cylindrical cavities. The equilibrium morphologies are obtained following an annealing strategy of a Landau-de Gennes free energy functional. Three dimensionless groups are identified to build phase diagrams: the natural twist, the ratio of elastic energies, and the circumscription of a BP cell. Curvature is shown to introduce helical features that are first observed as a Double Twist, and progress to Chiral Ribbons and, ultimately, Helical BP and BP. Chiral ribbons are examined as useful candidates for driven assembly given their tunability and robustness.

Prevalencia de infarto de miocardio sin enfermedad coronaria aterosclerótica obstructiva (MINOCA) / Prevalence of myocardial infarction with non-obstructive atherosclerotic coronary artery disease (MINOCA)

Resumen Objetivo: Determinar la prevalencia y factores de riesgo cardiovascular de los pacientes con infarto agudo de miocardio sin evidencia de lesiones coronarias obstructivas en la arteriografía coronaria, en una institución de salud con servicios de mediana y alta complejidad en la ciudad de Valledupar (Cesar), Colombia. Materiales y métodos: Estudio descriptivo, de corte transversal, único centro, en el que se incluyeron pacientes mayores de 18 años, atendidos en un centro hospitalario en la ciudad de Valledupar con síndrome coronario agudo, a quienes se les realizó arteriografía coronaria y cumplían con los criterios para MINOCA según la cuarta definición universal de infarto de miocardio, desde enero de 2016 hasta diciembre de 2019. Se calculó la prevalencia de MINOCA y descripción por sexo, edad, factores de riesgo cardiovascular y tipo de presentación del SCA. Resultados: De un total de 3.022 pacientes de la población estudiada con diagnóstico de infarto agudo de miocardio, 215 no tenían lesiones coronarias obstructivas, lo cual arrojó una prevalencia del 7.11% (IC 95%: 6.20-8.03%). La mayoría fueron mujeres (53.02%) con una edad promedio de 56,6 años. El 75.8% de los pacientes tenía al menos un factor de riesgo cardiovascular, con predominio de hipertensión arterial (67.4 %). La mayoría presentó síndrome coronario agudo sin elevación del segmento ST (93.5%). Conclusión: La prevalencia de MINOCA en nuestra institución se encuentra en el rango descrito en la literatura médica y tiene características clínicas similares en reportes publicados. Se plantea la necesidad de realizar estudios posteriores para la determinación de la causa en este tipo de pacientes.

Abstract Objective: To determine the prevalence and cardiovascular risk factors in patients with acute myocardial infarction with non-obstructive coronary lesions in coronary arteriography in a health institution with intermediate and specialized care in the city of Valledupar (Cesar), Colombia. Materials and methods: This was a descriptive, cross-sectional, single-center study. All patients included were over 18 years of age. They presented an acute coronary syndrome and were treated in a health center in Valledupar, Colombia. Coronary arteriography was completed, and patients met the criteria for MINOCA according to the fourth universal definition of myocardial infarction. The prevalence of MINOCA and description by sex, age, cardiovascular risk factors, and type of ACS presentation were calculated. The study was carried out between January 2016 and December 2019. Results: Of the 3.022 patients diagnosed with acute myocardial infarction, 215 did not have non-obstructive coronary lesions, with a prevalence of 7.11% (CI 95%: 6.20-8.03%). Most subjects were women (53.02 %), and the mean age was 56.6 years. 75.8% of participants had at least one cardiovascular risk factor, predominantly arterial hypertension (67.4%). Most patients had non-ST-segment elevation acute coronary syndrome (93.5%). Conclusion: The prevalence of MINOCA in our institution is within the range described in the medical literature. The clinical characteristics found were similar to those reported in the literature. Further studies need to be conducted to determine the cause in this type of patient.

Short-term administration of tibolone reduces inflammation and oxidative stress in the hippocampus of ovariectomized rats fed high-fat and high-fructose.

Inflammation and oxidative stress are critical events involved in neurodegeneration. In animal models, it has been shown that chronic consumption of a hypercaloric diet, which leads to inflammatory processes, affects the hippocampus, a brain region fundamental for learning and memory processes. In addition, advanced age and menopause are risk factors for neurodegeneration. Hormone replacement therapy (HRT) ameliorates menopause symptoms. Tibolone (TB), a synthetic hormone, exerts estrogenic, progestogenic and androgenic effects on different tissues. We aimed to determine the effect of short-term TB administration on oxidative stress and inflammation markers in the hippocampus of ovariectomized rats fed a high-fat-and-fructose diet (HFFD). Adult female rats were ovariectomized (OVX) and fed standard diet or HFFD-consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water-and administered vehicle or TB (1 mg/kg for seven days). Finally, we administered hormone receptor antagonists (MPP, RU486 or FLU) to each of the OVX + HFFD + TB groups. Bodyweight, triglycerides and cholesterol, oxidative stress and inflammation markers, and the activity and expression of antioxidant enzymes were quantified in the hippocampus of each experimental group. We observed that short-term TB administration significantly reduced body weight, AGEs, MDA levels, increased SOD and GPx activity, improved GSH/GSSG ratio, and reduced IL-6 and TNF-α. Our findings suggest that short-term administration of TB decreases oxidative stress and reduces inflammation caused by HFFD and early estrogenic decline. These effects occurred via estrogen receptor alpha.

4-Hydroxybenzoic Acid and ß-Sitosterol from Cucurbita ficifolia Act as Insulin Secretagogues, Peroxisome Proliferator-Activated Receptor-Gamma Agonists, and Liver Glycogen Storage Promoters: In Vivo, In Vitro, and In Silico Studies.

Insulin secretion and GLUT4 expression are two critical events in glucose regulation. The receptors G-protein-coupled receptor 40 (GPR40) and peroxisome proliferator-activated receptor-gamma (PPARγ) modulate these processes, and they represent potential therapeutic targets for new antidiabetic agent's design. Cucurbita ficifolia fruit is used in traditional medicine for diabetes control. Previous studies demonstrated several effects: a hypoglycemic effect mediated by an insulin secretagogue action, antihyperglycemic effect, and promoting liver glycogen storage. Anti-inflammatory and antioxidant effects were also reported. Moreover, some of its phytochemicals have been described, including d-chiro-inositol. However, to understand these effects integrally, other active principles should be investigated. The aim was to perform a chemical fractionation guided by bioassay to isolate and identify other compounds from C. ficifolia fruit that explain its hypoglycemic action as insulin secretagogue, its antihyperglycemic effect by PPARγ activation, and on liver glycogen storage. Three different preparations of C. ficifolia were tested in vivo. Ethyl acetate fraction derived from aqueous extract showed antihyperglycemic effect in an oral glucose tolerance test and was further fractioned. The insulin secretagogue action was tested in RINm5F cells. For the PPARγ activation, C2C12 myocytes were treated with the fractions, and GLUT4 mRNA expression was measured. Chemical fractionation resulted in the isolation and identification of ß-sitosterol and 4-hydroxybenzoic acid (4-HBA), which increased insulin secretion, GLUT4, PPARγ, and adiponectin mRNA expression, in addition to an increase in glycogen storage. 4-HBA exhibited an antihyperglycemic effect, while ß-sitosterol showed hypoglycemic effect, confirming the wide antidiabetic related results we found in our in vitro models. An in silico study revealed that 4-HBA and ß-sitosterol have potential as dual agonists on PPARγ and GPR40 receptors. Both compounds should be considered in the development of new antidiabetic drug development.

Antinociceptive and gastroprotective activities of Bocconia arborea S. Watson and its bioactive metabolite dihydrosanguinarine in murine models.

ETHNOPHARMACOLOGICAL RELEVANCE: Bocconia arborea S. Watson (Papaveraceae) is known as "palo llora sangre" and is used in Mexican traditional medicine for the treatment of infections, it is also used as anxiolytic, analgesic, and antidiabetic, among others. AIM OF THE STUDY: to evaluate the antinociceptive and gastroprotective activities of extracts from B. arborea and dihydrosanguinarine (DHS) in murine models. MATERIALS AND METHODS: Organic extracts [hexane (HEX), dichloromethane (DCM) and methanol (MeOH)] were obtained by maceration. DHS was isolated and purified from HEX and DCM by precipitation and chromatographic column, respectively. Organic extracts and DHS were evaluated to determine their antinociceptive effect using formalin test in murine model. Also, the ambulatory effect of the HEX and DHS was determined in Open field test. The possible mechanism of action of DHS was explored in the presence of naltrexone (NTX, 1 mg/kg, i.p.), and picrotoxin (PTX, 1 mg/kg, i.p.). Gastric damage as possible adverse effect or gastroprotection were also investigated. Whereas DHS acute toxicological study was done, and 100 mg/kg of DHS was examined by electroencephalographic (EEG) analysis to discard neurotoxic effects. RESULTS: The B. arborea extracts significantly showed effects in both neurogenic and inflammatory phases of the formalin test, where the HEX extract reached the major antinociceptive effect. A significant and dose-response (10, 30, and 100 mg/kg) antinociceptive activity was observed with the HEX (ED50 = 69 mg/kg) and DHS (ED50 = 85 mg/kg) resembling the effect of the reference analgesic drug tramadol (30 mg/kg). The significant effect of DHS was inhibited in the presence of NTX and PTX. Neither the extracts or DHS produced sedative effects or gastric damage per se at antinociceptive doses. The EEG analysis demonstrated central depressant activity but not sedative or neurotoxic effects at the highest antinociceptive dosage tested, and LD50 is higher than 2000 mg/kg. CONCLUSIONS: HEX, DCM, and MeOH extracts showed significant antinociceptive activity, and DHS was identified as one of bioactive compounds without producing sedative, neurotoxic or gastric damage effects, as possible adverse effects reported for analgesic drugs. A role of opioid and GABAA neurotransmission appears to be involved as mechanisms of action of DHS, suggesting its potential for pain therapy and reinforcing the traditional use of B. arborea.

Determination of liquid-vapor equilibrium and critical properties of fatty acids for biodiesel production through molecular dynamics.

In recent years, biodiesel production has emerged as an option for renewable and green fuel generation due to the constant reduction of fossil fuel reservoirs. Biofuels as biodiesel also show valuable attributes, environmentally speaking, due to their low environmental impact, contributing to the achievement of sustainability. However, costs are not allowable for large-scale production. Thereby, several novel processes have been proposed (e.g., reactive distillation) to solve this issue. An inconvenience for the development of these processes is the little information in the literature about the critical properties of fatty acids, which are precursors of biodiesel. Determination of critical properties for fatty acids through experimentation is difficult. The reason is that fatty acids tend to self-associate (to dimerize) due to carboxylic groups presence through hydrogen bonds, and consequently, have higher boiling points than other compounds of similar molecular mass (e.g., hydrocarbons, esters). Therefore, alternative methods for this determination are required. One choice is the group-contribution method, which is based on the structure of the molecule; however, results can significantly vary among different group-contribution approaches. Another alternative (and the focus of this research) for the determination of these properties is molecular simulation techniques. In this work, the liquid-vapor equilibrium as a function of temperature and the surface tension of three pure fatty acids of long chain (linoleic, oleic, and palmitic acid) have been calculated. Simulations have been performed by molecular dynamics using the method of direct determination of phase coexistence with the software GROMACS; in which the transferable potentials for phase equilibria united atom forcefield (TraPPE-UA) have been implemented for these specific molecules. Orthobaric densities and surface tension values have been reported at temperatures near the critical point (from 650 K to 800 K). Critical properties (temperature, pressure, density) have been extrapolated from trajectories obtained in these simulations using scaling law relations. Critical properties for these compounds are not available experimentally, therefore, group contribution calculations from the literature were used as a reference. In this comparison, the palmitic acid properties calculated in this work, show the best agreement among the three substances investigated.

Dynamics and phase behavior of two-dimensional size-asymmetric binary mixtures of core-softened colloids.

The self-assembly of binary colloidal mixtures provides a bottom-up approach to create novel functional materials. To elucidate the effect of composition, temperature, and pressure on the self-assembly behavior of size-asymmetric mixtures, we performed extensive dynamics simulations of a simple model of polymer-grafted colloids. We have used a core-softened interaction potential and extended it to represent attractive interactions between unlike colloids and repulsions between like colloids. Our study focused on size-asymmetric mixtures where the ratio between the sizes of the colloidal cores was fixed at σBσA=0.5. We have performed extensive simulations in the isothermal-isobaric and canonical (NVT) ensembles to elucidate the phase behavior and dynamics of mixtures with different stoichiometric ratios. Our simulation results uncovered a rich phase behavior, including the formation of hierarchical structures with many potential applications. For compositions where small colloids are the majority, sublattice melting occurs for a wide range of densities. Under these conditions, large colloids form a well-defined lattice, whereas small colloids can diffuse through the system. As the temperature is decreased, the small colloids localize, akin to a metal-insulator transition, with the small colloids playing a role similar to electrons. Our results are summarized in terms of phase diagrams.

Synthesis, molecular docking, dynamic simulation and pharmacological characterization of potent multifunctional agent (dual GPR40-PPARγ agonist) for the treatment of experimental type 2 diabetes.

The current manuscript describes two molecules that were designed against PPARγ and GPR40 receptors. The preparation of the compounds was carried out following a synthetic route of multiple steps. Then, the mRNA expression levels of PPARγ, GLUT4, and GPR40 induced by compounds were measured and quantified in adipocyte and ß-pancreatic cell cultures. The synthesized compound 1 caused an increase in the 4-fold expression of mRNA of PPARγ regarding the control and had a similar behavior to the pioglitazone, while compound 2 only increased 2-fold the expression. Also, the compound 1 increased to 7-fold the GLUT4 expression levels, respect to the control and twice against the pioglitazone. On the other hand, the 1 increase 3-fold GPR40 expression, and compound 2 had a minor activity. Besides, 1 and 2 showed a moderated increase on insulin secretion and calcium mobilization versus the glibenclamide. Based on the molecular docking studies, the first compound had a similar conformation to co-crystal ligands into the binding site of both receptors. The poses were docked keeping the most important interactions and maintaining the interaction along the Molecular Dynamics simulation (20 ns). Finally, compound (1) showed an antihyperglycemic effect at 5 mg/kg, however at higher doses of 25 mg/kg it controlled blood glucose levels associated with feeding intake and without showing the adverse effects associated with insulin secretagogues (hypoglycemia). For these reasons, we have concluded that molecule 1 acts as a dual PPARγ and GPR40 agonist offering a better glycemic control than current treatments.

Glycine is a competitive antagonist of the TNF receptor mediating the expression of inflammatory cytokines in 3T3-L1 adipocytes.

OBJECTIVE: To determine the involvement of TNF-α and glycine receptors in the inhibition of pro-inflammatory adipokines in 3T3-L1 cells. METHODS: RT-PCR evidenced glycine receptors in 3T3-L1 adipocytes. 3T3-L1 cells were transfected with siRNA for the glycine (Glrb) and TNF1a (Tnfrsf1a) receptors and confirmed by confocal microscopy. Transfected cells were treated with glycine (10 mM). The expressions of TNF-α and IL-6 mRNA were measured by qRT-PCR, while concentrations were quantified by ELISA. RESULTS: Glycine decreased the expression and concentration of TNF-α and IL-6; this effect did not occur in the absence of TNF-α receptor due to siRNA. In contrast, glycine produced only slight changes in the expression of TNF-α and IL-6 in the absence of the glycine receptor due to siRNA. A docking analysis confirmed the possibility of binding glycine to the TNF-α1a receptor. CONCLUSION: These findings support the idea that glycine could partially inhibit the binding of TNF-α to its receptor and provide clues about the mechanisms by which glycine inhibits the secretion of pro-inflammatory adipokines in adipocytes through the TNF-α receptor.

Directing the far-from-equilibrium assembly of nanoparticles in confined liquid crystals by hydrodynamic fields.

The assembly of nematic colloids relies on long-range elastic interactions that can be manipulated through external stimuli. Confinement and the presence of a hydrodynamic field alter the defect structures and the energetic interactions between the particles. In this work, the assembly landscape of nanoparticles embedded in a nematic liquid crystal confined in a nanochannel under a pressure-driven flow is determined. The dynamics of the liquid crystal tensor alignment field is determined through a Poisson-Bracket framework, namely the Stark-Lubensky equations, coupled with the zero-Reynolds momentum equations and the liquid crystal Landau-de Gennes free energy functional. A second order semi-implicit time integration and a three-dimensional Galerkin finite element method are used to resolve flow and nematic fields under several conditions. In general, the zero Reynolds flow displaces the defects around the particles in the upstream direction and renders the surface anchoring ineffective when the flow strength dominates over the nematic elasticity. More importantly, the potential of mean force for particle assembly is non-monotonic independent of surface anchoring. Our results show that the confinement length scale determines the repulsion/attraction transition between colloids, while the flow strength modifies the static defect structure surrounding the particles and determines the magnitude of the energetic barrier for successful assembly. In the attractive regime, the particles move at different rates through the nematic until one particle eventually catches up with the other. This process occurs against or along the direction of flow depending on the flow strength. Ultimately, these results provide a template for engineering and controlling the transport and assembly of nanoparticles under far-from equilibrium conditions in anisotropic media.

Antihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: In vivo, functional ex vivo and in silico studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Achillea millefolium L. (Asteraceae), known as yarrow (milenrama), is a plant used in Mexican traditional medicine for the treatment of hypertension, diabetes, and related diseases. AIM: To determine the vasorelaxant and antihypertensive effect of A. millefollium and to isolate the main bioactive antihypertensive agents. MATERIALS AND METHODS: Organic (hexane, dichloromethane and methanol) and hydro-alcohol (Ethanol-H2O: 70:30) extracts obtained from flowers, leaves and stems were evaluated on isolated aorta rat rings with and without endothelium to determine their vasorelaxant effect. Hexane extract from flowers (HEAmF) was studied to evaluate its antihypertensive effect on spontaneously hypertensive rats (SHR). From HEAmF, bioactive compounds were obtained by bio-guided phytochemical separation through chromatography. RESULTS: Organic extracts showed the best vasorelaxant activity. Hexane extract from flowers was the most potent and efficient ex vivo vasorelaxant agent, showing significant decrease of systolic and diastolic blood pressure in SHR (p < 0.05). Phytochemical separation of HEAmF yielded two epimeric sesquiterpene lactones: leucodin (1) and achillin (2), the major components of the extract. Both 1 and 2 showed similar vasorelaxant action ex vivo (p < 0.05), and their effects where modified by L-NAME (10 µM, nitric oxide synthase inhibitor), by ODQ (1 µM, soluble guanylyl cyclase inhibitor), and also relaxed the contraction induced by KCl (80 mM). Finally, 1 and 2 intragastric administration (50 mg/kg) decreased systolic and diastolic blood pressure in SHR. CONCLUSIONS: Achillea millefolium showed antihypertensive and vasorelaxant effects, due mainly to leucodin and achillin (epimers). Both compounds showed antihypertensive activity by vasorelaxation putatively by endothelium-dependent NO release and cGMP increase, as well as by calcium channels blockade.

Oleanolic acid induces a dual agonist action on PPARγ/α and GLUT4 translocation: A pentacyclic triterpene for dyslipidemia and type 2 diabetes.

Type 2 diabetes (T2D) is a metabolic disease characterized by defects in glycemia regulation. This disease is associated with alterations in insulin action and lipid metabolism, generating hyperglycemia and dyslipidemias. Currently, it is necessary to develop new or known drugs that promote the sensitization of insulin action. Thus, activation of peroxisome proliferator-activated receptors (PPARs) is probably the key to doing this. PPARs participate in maintaining an energetic balance between storage and the expenditure of energy. The activation of PPARγ produces the storage of energy, mainly as glycogen and fat. Meanwhile, PPARα activation promotes lipid degradation. Oleanolic acid (OA), a pentacyclic triterpenoid of numerous edible and medicinal plants, decreases hyperglycemia and lipid accumulation. However, the effects on PPARs and their regulated genes are unknown. Our aim was to determine the effects of OA on PPAR γ/α expression and their regulated genes (adiponectin, type 4 glucose transporter, fatty acid transport protein, and long-chain acyl-CoA synthetase) in C2C12 myoblasts by RT-PCR, Western blot, GLUT-4 translocation, and lipid storage in 3T3-L1 adipocytes. In C2C12 myoblasts, OA increased the expression of mRNA in both PPARγ/α and their regulated genes; also, PPARγ, GLUT-4, and FATP-1 protein expression increased, as well as GLUT-4 translocation. In 3T3-L1, OA increased the expression of mRNA in both PPARγ/α and maintained lipid storage unchanged. In conclusion, OA exhibited a dual action on PPARγ/α, which might explain in part its antihyperglycemic effect. This compound represents an alternative for designing novel therapeutic strategies in the control of T2D.

Cuboidal liquid crystal phases under multiaxial geometrical frustration.

Cuboidal liquid crystal phases - the so-called blue phases - consist of a network of topological defects arranged into a cubic symmetry. They exhibit striking optical properties, including Bragg reflection in the visible range and fast response times. Confining surfaces can interfere with the packing of such a network, leading to structures that have not been explored before. In this work, a Landau-de Gennes free energy formalism for the tensor alignment field Q is used to investigate the behavior of chiral liquid crystals under non-isotropic confinement. The underlying free energy functional is solved by relying on a Monte Carlo method that facilitates efficient exploration of configuration space. The results of simulations are expressed in terms of phase diagrams as a function of chirality and temperature for three families of spheroids: oblate, spherical, and prolate. Upon deformation, blue phases adapt and transform to accommodate the geometrical constraints, thereby resulting in a wider range of thermal stability. For oblate spheroids, confinement interferes with the development of a full blue phase structure, resulting on a combination of half skyrmions. For prolate spheroids, the blue phases are hybridized and exhibit features of blue phases I and II. More generally, it is shown that mechanical deformation provides an effective means to control, manipulate and stabilize blue phases and cholesterics confined in tactoids.

Efficacy of the Combination of Pinaverium Bromide 100 mg Plus Simethicone 300 mg in Abdominal Pain and Bloating in Irritable Bowel Syndrome: A Randomized, Placebo-controlled Trial.

GOALS: We aimed to evaluate the efficacy and safety of PB+S (pinaverium bromide 100 mg plus simethicone 300 mg) in patients with irritable bowel syndrome (IBS). BACKGROUND: IBS is a multifactorial disorder; thus, combination therapy with different mechanisms of action is expected to be useful. PB+S has shown effectiveness in an open-label clinical study in IBS. However, there are no placebo-controlled trials. MATERIALS AND METHODS: IBS-Rome III patients with abdominal pain/discomfort for at least 2 days within the week prior to baseline assessment were included in this 12-week, randomized, double-blind, placebo-controlled study of PB+S versus placebo, bid. The primary endpoint was overall symptom improvement, evaluated weekly by the patient (Likert Scale). Secondary endpoints included the weekly improvement in the severity of abdominal pain and bloating assessed both by patients (10-cm Visual Analogue Scale) and investigators (Likert Scale); frequency of Bristol Scale stool types (consistency) evaluated by patients and the IBS Quality of Life scores. RESULTS: A total of 285 patients (female: 83%; 36.5±8.9 y old) received at least 1 dose of PB+S (n=140) or placebo (n=145). No difference was observed in overall symptom improvement between the groups (P=0.13). However, PB+S was superior in abdominal pain (effect size: 31%, P=0.038) and bloating (33%, P=0.019). Patients with IBS-C and IBS-M showed the best improvement in the frequency of stool types with PB+S. No differences were observed in IBS Quality of Life scores and adverse events. CONCLUSIONS: PB+S was superior to placebo in improving abdominal pain and bloating in patients with active IBS. The effect on the frequency of stool consistency was particularly significant in IBS-C and IBS-M.

Hierarchical complex self-assembly in binary nanoparticle mixtures.

Hierarchical self-assembly of soft matter provides a powerful route to create complex materials with enhanced physical properties. The understanding of the fundamental processes leading to such organization can provide design rules to create new functional materials. In this work, we use a simple model of polymer-grafted nanoparticles to explore the self-assembly of binary mixtures. By using Monte Carlo simulations we study the interplay of composition, density and particle sizes on the self-organization of such nanoparticle systems. It is found that complex hierarchical organization can take place for conditions where one-component systems form simple lattices. In particular, a mixture where one component forms a structure with 18-fold symmetry in a sea of an apparent disordered phase of the second component is observed to emerge for certain parameter combinations.

Fluctuations and phase transitions of uniaxial and biaxial liquid crystals using a theoretically informed Monte Carlo and a Landau free energy density.

In this work, we explore fluctuations during phase transitions of uniaxial and biaxial liquid crystals using a phenomenological free energy functional. We rely on a continuum-level description of the liquid crystal ordering with a tensorial parameter and a temperature dependent Landau polynomial expansion of the tensor's invariants. The free energy functional, over a three-dimensional periodic domain, is integrated with a Gaussian quadrature and minimized with a theoretically informed Monte Carlo method. We reconstruct analytical phase diagrams, following Landau and Doi's notations, to verify that the free energy relaxation reaches the global minimum. Importantly, our relaxation method is able to follow the thermodynamic behavior provided by other non-phenomenological approaches; we predict the first order character of the isotropic-nematic transition, and we identify the uniaxial-biaxial transition as second order. Finally, we use a finite-size scaling method, using the nematic susceptibility, to calculate the transition temperatures for 4-Cyano-4'-pentylbiphenyl (5CB) and N-(4-methoxybenzylidene)-4-butylaniline (MBBA). Our results show good agreement with experimental values, thereby validating our minimization method. Our approach is an alternative towards the relaxation of temperature dependent continuum-level free energy functionals, in any geometry, and can incorporate complicated elastic and surface energy densities.

Triterpenoids from Hibiscus sabdariffa L. with PPARδ/γ Dual Agonist Action: In Vivo, In Vitro and In Silico Studies.

Hibiscus sabdariffa is a medicinal plant consumed as a diuretic and anti-obesity remedy. Several pharmacological studies have shown its beneficial effects in metabolism. Peroxisome proliferator-activated receptors δ and γ may play a role in the actions of H. sabdariffa. These nuclear receptors regulate lipid and glucose metabolism and are therapeutic targets for type 2 diabetes. This research aimed to perform a phytochemical study guided by a bioassay from H. sabdariffa to identify compounds with peroxisome proliferator-activated receptor δ and peroxisome proliferator-activated receptor γ agonist activity, supported by messenger ribonucleic acid expression, molecular docking, lipid accumulation, and an antihyperglycemic effect. An oral glucose tolerance test in mice with the aqueous extract of H. sabdariffa and the dichloromethane extract of H. sabdariffa was performed. The dichloromethane extract of H. sabdariffa exhibited an antihyperglycemic effect. The dichloromethane extract of H. sabdariffa was fractioned, and four fractions were evaluated in 3T3-L1 adipocytes on peroxisome proliferator-activated receptor δ, peroxisome proliferator-activated receptor γ, fatty acid transporter protein, and glucose transporter type 4 messenger ribonucleic acid expression. Fraction F3 exhibited peroxisome proliferator-activated receptor δ/γ dual agonist activity, and a further fractionation yielded two subfractions, F3-1 and F3-2, which also increased peroxisome proliferator-activated receptor δ and peroxisome proliferator-activated receptor γ expression. Subfractions were analyzed by GC/MS. The main compounds identified in F3-1 were linoleic acid, oleic acid, and palmitic acid, while in F3-2, the main compounds identified were α-amyrin and lupeol. These molecules were subjected to molecular docking analysis. α-Amyrin and lupeol showed the highest affinity. Moreover, both produced an increase in peroxisome proliferator-activated receptor δ, peroxisome proliferator-activated receptor γ, fatty acid transporter protein, and glucose transporter type 4 expression. Additionally, α-amyrin and lupeol decreased lipid accumulation in 3T3-L1 adipocytes and blood glucose in mice. Until now, α-amyrin and lupeol have not been reported with activity on peroxisome proliferator-activated receptors. This study provides evidence that α-amyrin and lupeol possess antidiabetic effects through a peroxisome proliferator-activated receptor δ/γ dual agonist action.

[Preacondicionamiento isquémico remoto sobre viabilidad del injerto hepático]. / Remote ischemic preconditioning in liver graft viability.

ANTECEDENTES: El preacondicionamiento isquémico remoto (PIR) en trasplante hepático ha sido sugerido en el ámbito experimental como estrategia para disminuir la lesión por isquemia- reperfusión. OBJETIVO: Evaluar el efecto del PIR sobre el injerto hepático en donante cadáver y el impacto de diversos mediadores inflamatorios en este proceso. MÉTODO: Se incluyeron 10 receptores de trasplante hepático, 5 controles y 5 con PIR, el cual fue realizado en los donantes cadavéricos mediante la aplicación de un torniquete neumático en ambos muslos por 10 minutos seguido de 10 minutos de reperfusión. Se determinaron interleucina (IL)-1, IL-6, factor de necrosis tumoral alfa (FNT-α), factor de crecimiento endotelial vascular (FCEV) y molécula de adhesión intracelular (ICAM)-1, parámetros hematológicos y bioquímicos en diversas fases del trasplante hepático. RESULTADOS: Se observó un aumento significativo de la aspartato aminotransferasa (AST), la alanino aminotransferasa (ALT) y la fosfatasa alcalina en las fases tempranas tras el trasplante hepático, y a las 72 horas los sujetos con PIR mostraron mejor respuesta, con recuperación de plaquetas, que persistió hasta los 3 meses en este grupo. La IL-6 participa en las fases tempranas de la lesión por isquemia- reperfusión, contrario al FNT-α, que se incrementa hasta el día 7, mientras que la ICAM-1 aumentó en todas las fases. CONCLUSIONES: En este estudio piloto, el PIR disminuyó el daño por lesión por isquemia- reperfusión, aunque el mayor efecto se observó después de 72 horas. BACKGROUND: Remote ischemic preconditioning (RIP) in liver transplantation has been suggested experimentally as a strategy to reduce ischemia-reperfusion injury. OBJECTIVE: Evaluate the effect of RIP on liver graft in cadaveric donors and the impact of various inflammatory mediators in this process. METHOD: Ten liver transplantation recipients, 5 controls and 5 PIR, were made in the cadaver donors by applying a pneumatic tourniquet in the upper third of both thighs for a period of 10 minutes followed by 10 minutes reperfusion. The determination of interleukine (IL)-1, IL-6, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), intracellular adhesion molecule (ICAM)-1 was performed as well as hematological and biochemical parameters at various stages of liver transplantation. RESULTS: Significant increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase in the early stages of post-liver transplantation were observed, after 72 hours subjects who received liver transplantation subjected to RIP they showed a better response, which was also evident in platelet recovery, which persisted until phase 3 months in this group. IL-6 appears to participate in the early stages of the ischemia-reperfusion injury, contrary to TNF-α that increases until day 7 while ICAM-1 was increased in all phases. CONCLUSIONS: In this pilot study the PIR decreased the damage by ischemia-reperfusion injury, although the greatest effect was observed after 72 hours.