Exploring ethylene insertion reaction mechanism in nickel complexes: a comparative study by the reaction force and reaction electronic flux in molecular and SiO2-supported catalysts.

CONTEXT: This study investigates the ethylene insertion reaction mechanism for polymerization catalysis, aiming to discern differences between Ni-α-imine ketone-type catalyst and their SiO2-supported counterpart. The reaction force analysis unveils a more intricate mechanism with SiO2 support, shedding light on unexplored factors and elucidating the observed lower catalytic activity. Furthermore, reactivity indexes suggest earlier ethylene activation in the supported catalyst, potentially enhancing overall selectivity. Finally, the reaction electronic flux analysis provides detailed insights into the electronic activity at each step of the reaction mechanism. In sum, this study offers a comprehensive understanding of the ethylene insertion reaction mechanism in both molecular and supported catalysts, underscoring the pivotal role of structural and electronic factors in catalytic processes. METHODS: Density functional theory (DFT) calculations were conducted using the ωB97XD functional and the 6-31 + G(d,p) basis sets with Gaussian16 software. Computational techniques utilized in this study encompassed the IRC method, reaction force analysis, and evaluation of electronic descriptors such as electronic chemical potential, molecular hardness, and electrophilicity reactivity indexes. Additionally, reaction electronic flux analysis was employed to investigate electronic activity along the reaction coordinate.

Interaction mechanism of water-soluble inorganic arsenic onto pristine nanoplastics.

Nanoplastics (NPLs) persist in aquatic habitats, leading to incremental research on their interaction mechanisms with metalloids in the environment. In this regard, it is known that plastic debris can reduce the number of water-soluble arsenicals in contaminated environments. Here, the arsenic interaction mechanism with pure NPLs, such as polyethylene terephthalate (PET), aliphatic polyamide (PA), polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP), and polystyrene (PS) is evaluated using computational chemistry tools. Our results show that arsenic forms stable monolayers on NPLs through surface adsorption, with adsorption energies of 9-24 kcal/mol comparable to those on minerals and composite materials. NPLs exhibit varying affinity towards arsenic based on their composition, with As(V) adsorption showing higher stability than As(III). The adsorption mechanism results from a balance between electrostatics and dispersion forces (physisorption), with an average combined contribution of 87%. PA, PET, PVC, and PS maximize the electrostatic effects over dispersion forces, while PE and PP maximize the dispersion forces over electrostatic effects. The electrostatic contribution is attributed to hydrogen bonding and the activation of terminal O-C, C-H, and C-Cl groups of NPLs, resulting in several pairwise interactions with arsenic. Moreover, NPLs polarity enables high mobility in aqueous environments and fast mass transfer. Upon adsorption, As(III) keeps the NPLs polarity, while As(V) limits subsequent uptake but ensures high mobility in water. The solvation process is destabilizing, and the higher the NPL polarity, the higher the solvation energy penalty. Finally, the mechanistic understanding explains how temperature, pressure, pH, salinity, and aging affect arsenic adsorption. This study provides reliable quantitative data for sorption and kinetic experiments on plastic pollution and enhances our understanding of interactions between water contaminants.

Modulation of Kynurenic Acid Production by N-acetylcysteine Prevents Cognitive Impairment in Adulthood Induced by Lead Exposure during Lactation in Mice.

Lead (Pb2+) exposure during early life induces cognitive impairment, which was recently associated with an increase in brain kynurenic acid (KYNA), an antagonist of NMDA and alpha-7 nicotinic receptors. It has been described that N-acetylcysteine (NAC) favors an antioxidant environment and inhibits kynurenine aminotransferase II activity (KAT II, the main enzyme of KYNA production), leading to brain KYNA levels decrease and cognitive improvement. This study aimed to investigate whether the NAC modulation of the brain KYNA levels in mice ameliorated Pb2+-induced cognitive impairment. The dams were divided into four groups: Control, Pb2+, NAC, and Pb2++NAC, which were given drinking water or 500 ppm lead acetate in the drinking water ad libitum, from 0 to 23 postnatal days (PNDs). The NAC and Pb2++NAC groups were simultaneously fed NAC (350 mg/day) in their chow from 0 to 23 PNDs. At PND 60, the effect of the treatment with Pb2+ and in combination with NAC on learning and memory performance was evaluated. Immediately after behavioral evaluation, brain tissues were collected to assess the redox environment; KYNA and glutamate levels; and KAT II activity. The NAC treatment prevented the long-term memory deficit exhibited in the Pb2+ group. As expected, Pb2+ group showed redox environment alterations, fluctuations in glutamate levels, and an increase in KYNA levels, which were partially avoided by NAC co-administration. These results confirmed that the excessive KYNA levels induced by Pb2+ were involved in the onset of cognitive impairment and could be successfully prevented by NAC treatment. NAC could be a tool for testing in scenarios in which KYNA levels are associated with the induction of cognitive impairment.

Mechanisms Associated with Cognitive and Behavioral Impairment Induced by Arsenic Exposure.

Arsenic (As) is a metalloid naturally present in the environment, in food, water, soil, and air; however, its chronic exposure, even with low doses, represents a public health concern. For a long time, As was used as a pigment, pesticide, wood preservative, and for medical applications; its industrial use has recently decreased or has been discontinued due to its toxicity. Due to its versatile applications and distribution, there is a wide spectrum of human As exposure sources, mainly contaminated drinking water. The fact that As is present in drinking water implies chronic human exposure to this metalloid; it has become a worldwide health problem, since over 200 million people live where As levels exceed safe ranges. Many health problems have been associated with As chronic exposure including cancer, cardiovascular diseases, gastrointestinal disturbances, and brain dysfunctions. Because As can cross the blood-brain barrier (BBB), the brain represents a target organ where this metalloid can exert its long-term toxic effects. Many mechanisms of As neurotoxicity have been described: oxidative stress, inflammation, DNA damage, and mitochondrial dysfunction; all of them can converge, thus leading to impaired cellular functions, cell death, and in consequence, long-term detrimental effects. Here, we provide a current overview of As toxicity and integrated the global mechanisms involved in cognitive and behavioral impairment induced by As exposure show experimental strategies against its neurotoxicity.

Computational Insights on the Chemical Reactivity of Functionalized and Crosslinked Polyketones to Cu2+ Ion for Wastewater Treatment.

Today, the high concentrations of copper found in water resources result in an urgent problem to solve since human health and aquatic ecosystems have been affected. Functionalized crosslinked polyketone resins (XLPK) have demonstrated high performance for the uptake of heavy metals in water solutions. In addition, its green chemical synthesis makes these resins very attractive as sorbents for metal ions contained in wastewater. XLPK are not soluble in aqueous media and do not require any catalyst, solvent, or harsh conditions to carry out the uptake process. In this paper, a series of functionalized XLPK with pending amino-derivatives namely; butylamine (BA), amino 2-propanol (A2P), 4-(aminomethyl) benzoic acid (HAMC), 6-aminohexanoic acid (PAMBA), and 1,2 diamino propane (DAP) directly attached to the pyrrole backbone of the polymers and crosslinked by di-amine derivatives was investigated using Density Functional Theory (DFT) calculations. Our computational analysis revealed that dipole-dipole interactions played a crucial role in enhancing the adsorption of Cu2+ ions onto XLPKs. The negatively charged ketone moieties and functional groups within XLPKs were identified as key adsorption sites for the selective binding of Cu2+ ions. Additionally, we found that XLPKs exhibited strong electrostatic interactions primarily through the -NH2 and -C=O groups. Evaluation of the adsorption energies in XLPK-Cu(II) complexes showed that the DAP-Cu(II) complex exhibited the highest stability, attributed to strong Cu(II)-N binding facilitated by the amino moiety (-NH2). The remaining XLPKs displayed binding modes involving oxygen atoms (Cu(II)-O) within the ketone moieties in the polymer backbone. Furthermore, the complexation and thermochemical analysis emphasized the role of the coordinator atom (N or O) and the coordinating environment, in which higher entropic effects involved in the adsorption of Cu2+ ions onto XLPKs describes a lower spontaneity of the adsorption process. The adsorption reactions were favored at lower temperatures and higher pressures. These findings provide valuable insights into the reactivity and adsorption mechanisms of functionalized and crosslinked polyketones for Cu2+ uptake, facilitating the design of high-performance polymeric resins for water treatment applications.

A novel scale based on biomarkers associated with COVID-19 severity can predict the need for hospitalization and intensive care, as well as enhanced probabilities for mortality.

Prognostic scales may help to optimize the use of hospital resources, which may be of prime interest in the context of a fast spreading pandemics. Nonetheless, such tools are underdeveloped in the context of COVID-19. In the present article we asked whether accurate prognostic scales could be developed to optimize the use of hospital resources. We retrospectively studied 467 files of hospitalized patients after COVID-19. The odds ratios for 16 different biomarkers were calculated, those that were significantly associated were screened by a Pearson's correlation, and such index was used to establish the mathematical function for each marker. The scales to predict the need for hospitalization, intensive-care requirement and mortality had enhanced sensitivities (0.91 CI 0.87-0.94; 0.96 CI 0.94-0.98; 0.96 CI 0.94-0.98; all with p < 0.0001) and specificities (0.74 CI 0.62-0.83; 0.92 CI 0.87-0.96 and 0.91 CI 0.86-0.94; all with p < 0.0001). Interestingly, when a different population was assayed, these parameters did not change considerably. These results show a novel approach to establish the mathematical function of a marker in the development of highly sensitive prognostic tools, which in this case, may aid in the optimization of hospital resources. An online version of the three algorithms can be found at: http://benepachuca.no-ip.org/covid/index.php.

Interaction mechanism of triclosan on pristine microplastics.

Urban wastewaters comprise different hydrophobic pollutants such as microplastics (MPs), pharmaceuticals, and personal care products. Among these pollutants, triclosan (TCS) shows a worrying interaction ability with MPs; recent studies show MPs serve as a vector between TCS and aquatic environments, whose interaction is still being studied to understand their combined toxicity and transport ability. Using computational chemistry tools, this work evaluates the TCS-MPs interaction mechanism, including pristine polymers, i.e., aliphatic polyamides (PA), polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), and polyethylene terephthalate (PET). Our results show that TCS adsorption on MPs solely occurs via physisorption, where PA reaches the higher adsorption ability. Remarkably, MPs reach higher or comparable adsorption stability than carbon-based materials, boron nitrides, and minerals, indicating their worrying transport properties. Also, the adsorption capacity is strongly influenced by entropy changes rather than thermal effects, which determine the different sorption capacities among polymers and agree well with reported sorption capacities from adsorption kinetic experiments in the literature. MPs show a polar and highly susceptible surface to establish electrostatics and dispersion effects on TCS. Accordingly, the TCS-MPs interaction mechanism arises from the interplay between electrostatics and dispersion forces, with a combined contribution of 81-93 %. Specifically, PA and PET maximize the electrostatic effects, while PE, PP, PVC, and PS maximize the dispersion effects. From the chemical viewpoint, TCS-MPs complexes interact by a series of pairwise interactions such as Van der Waals, hydrogen bonding, C-H⋯π, C-H⋯C-H, C-Cl⋯C-H, and C-Cl⋯Cl-C. Finally, the mechanistic information explains the effects of temperature, pressure, aging, pH, and salinity on TCS adsorption. This study quantitatively elucidates the interaction mechanism of TCS-MP systems, which were hard to quantify to date, and explains the TCS-MPs sorption performance for sorption/kinetic studies.

Systemic Disease Associations in a Cohort of Hispanic Patients with Scleritis.

(1) Purpose: A patient with scleritis may have an associated systemic disease, which is often autoimmunological and seldom infectious in origin. The data regarding such associations in Hispanic populations are scarce. Therefore, we evaluated the clinical characteristics and systemic-disease associations of a cohort of Hispanic patients with scleritis. (2) Methods: A retrospective review of the medical records (January 1990-July 2021) of two private uveitis practices in Puerto Rico was performed. Clinical characteristics and systemic-disease associations observed either at presentation or diagnosed as a consequence of the initial workup were recorded. (3) Results: A total of 178 eyes of 141 patients diagnosed with scleritis were identified. An associated autoimmune disease was present in 33.3% of the patients (rheumatoid arthritis, 22.7%; Sjögren's syndrome, 3.5%; relapsing polychondritis, 2.8%; sarcoidosis, 1.4%; systemic lupus erythematosus, 1.4%; and systemic vasculitis, 0.7%). An associated infectious disease was present in 5.7% of the patients (2.13%, syphilis; 1.41%, herpes simplex; 1.14%, herpes zoster; and 0.71%, Lyme disease). One patient had all-trans retinoic-acid-associated scleritis. Statistical analysis revealed that patients with nodular anterior scleritis were less likely to have an associated immune-mediated disease (OR: 0.21; p = 0.011). (4) Conclusion: Rheumatoid arthritis was the most common systemic autoimmune disease association, while syphilis was the most common infectious disease associated with scleritis patients. Our study suggests that patients with nodular scleritis have a lower risk of having an associated immune-mediated disease.

Mechanistic insights into the adsorption of endocrine disruptors onto polystyrene microplastics in water.

Microplastics and endocrine disruptors (EDs) are contaminants of emerging concerns and ubiquitously present in aquatic ecosystems, establishing interactions that still are the subject of investigation due to their implications in the cotransport of pollutants. Then, we conducted mechanistic studies based on state-of-art computational chemistry methods to quantitatively understand the interaction mechanisms whereby polystyrene micro or nanoplastics (PS-MPs) interact with representative classes of EDs in water (Ethynylestradiol, Estradiol, and Bisphenol A). The results showed that PS-MPs increase their charge distribution when forming microparticles in water, giving a permanent dipole that explains their increasing solubility in aqueous conditions. In agreement with experimental assessments, the PS-MPs favorably adsorb EDs with adsorption energies larger than 15 kcal/mol, even with comparable stability to nanostructured materials for adsorption, removal, and/or analysis of pollutants. The adsorption occurs via physisorption without covalent binding, bond breaking, or structural preparation energies, where the molecular structure of EDs can favor inner or outer surface adsorption depending on the molecular structure of the adsorbates. A balanced contribution of dispersion and electrostatic stabilizing effects determines the interaction mechanisms, accounting for a whole contribution of 88-90%. The electrostatic contribution emerges from the favorable alignment of the PS-MPs and EDs dipoles upon interaction due to the mild charge transfer between them in solution. In contrast, the dispersion contribution emerges from electron-electron interactions due to the permanent dipoles in adsorbates and adsorbents. Furthermore, thermochemical analyses clarify the role of temperature and pressure effects on the relative adsorption stability among EDs in aquatic environments. Therefore, modeling the adsorption process contributes to new knowledge on the sorption properties of PS-MPs, providing a mechanistic basis to understand the cotransport of pollutants in water environments and their impacts on environmental pollution.

The interaction mechanism of polystyrene microplastics with pharmaceuticals and personal care products.

Microplastics (MPs) have been detected in the hydrosphere, with hazardous implications in transporting coexisting water pollutants. Our knowledge about the interaction mechanisms that MPs establish with organic pollutants are still growing, which is essential to understand the adsorption properties of MPs and their relative stability with adsorbates. Here, we used classical (force field methods) and ab-initio (density functional theory) computational chemistry tools to characterize the interaction mechanisms between Polystyrene-MPs (PS-MPs) and pharmaceuticals/personal care products (PPCPs). Adsorption conformations and energies, thermochemistry, binding, and energy decomposition analyses were performed to obtain the quantitative mechanistic information. Our results show that PS-MPs have permanent dipoles, increasing the interaction with neutral PPCPs while repelling the charged pollutants; in all cases, a stable physisorption takes place. Moreover, PS-MPs increase their solubility upon pollutant adsorption due to an increase in the dipole moment, increasing their co-transport ability in aqueous environments. The stability of the PS-MPs/PPCPs complexes is further confirmed by thermochemical and molecular dynamics trajectory analysis as a function of temperature and pressure. The interaction mechanism of high pKa pollutants (pKa > 5) is due to a balanced contribution of electrostatic and dispersion forces, while the adsorption of low pKa pollutants (pKa < 5) maximizes the electrostatic forces, and steric repulsion effects explain their relative lower adsorption stability. In this regard, several pairwise intermolecular interactions are recognized as a source of stabilization in the PS-MPs/PPCPs binding: hydrogen bonding, π-π, OH⋯π, and CH⋯π, CCl⋯CH and CH⋯CH interactions. The ionic strength in solution slightly affects the adsorption stability of neutral PPCPs, while the sorption of charged pollutants is enhanced. This mechanistic information provides quantitative data for a better understanding of the interactions between organic pollutants and MPs, serving as valuable information for sorption/kinetic studies.

Atmospheric microplastics and nanoplastics as vectors of primary air pollutants - A theoretical study on the polyethylene terephthalate (PET) case.

Polyethylene terephthalate (PET) microplastics and nanoplastics are ubiquitously present in the atmosphere as atmospheric and airborne forms (PET-aMPs). Using first-principles calculations, we analyze the uptake of primary air pollutants onto PET-aMPs, focusing on their stabilities, adsorption mechanisms, and thermochemistry. The results show that PET-aMPs are selective for the spontaneous adsorption of CO, CO2, NO, N2O, NO2, NH3, and SO2, reaching stable adsorption energies of 6-20 kcal/mol per molecule, with comparable uptake ability than carbon-based materials, metals/metalloids, and metal oxide surfaces. Then, PET-aMPs become a vector for coexisting air pollutants in the atmosphere, which adsorb by inner or outer adsorption depending on the molecular polarity (dipole moment) and atomic constitution (electronegativity) of gaseous molecules. Also, atmospheric H2O and O2 are not competitive molecules, and ozone could enhance adsorption due to surface oxidation and structure breakdown. The interplay of electrostatic (46-61%) and dispersion forces (21-58%) drives the adsorption mechanism, where low-polar pollutants display almost a balanced electrostatic vs. dispersion contribution, while high polar molecules display a higher electrostatic stabilization. The outer adsorption is reached by strong dispersion, hydrogen bonding, and dipole-dipole-induced pairs, while lone-pair-π interactions appear in the inner adsorption regime. These results expand the understanding of the hazards and risks of atmospheric and airborne microplastics/nanoplastics, their impacts, co-transport ability, and interaction with the environment.

Characterization of Redox Environment and Tryptophan Catabolism through Kynurenine Pathway in Military Divers' and Swimmers' Serum Samples.

Endurance and resistance exercises, alone or in combination, induce metabolic changes that affect tryptophan (Trp) catabolism. The kynurenine pathway (KP) is the main route of Trp degradation, and it is modulated by the inflammatory and redox environments. Previous studies have shown that KP metabolites work as myokines that mediate the positive systemic effects related to exercise. However, it is poorly understood how different exercise modalities and intensities impact the KP. The aim of this study was to characterize the effect of two different exercise modalities, military diving and swimming, on the KP and the redox environment. A total of 34 healthy men from the Mexican Navy were included in the study, 20 divers and 14 swimmers, who started and stayed in military training consistently during the six months of the study; 12 Mexican men without fitness training were used as the control group. Physical fitness was determined at the beginning and after 6 months of training; criteria included body composition; serum levels of Trp, kynurenine (KYN), kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK); the glutathione ratio (GSH/GSSG); and malondialdehyde (MDA).. Results showed a significant loss of body fat in both the diver and swimmer groups. Compared with the control group, divers showed a decrease in Trp and 3-HK levels, but no changes were observed in the KYN/Trp, KYNA/Trp or 3-HK/Trp ratios, while swimmers showed a decrease in KYN levels and an increase in the KYNA and 3-HK levels. Additionally, divers showed a decrease in the GSH/GSSG ratio and an increase in MDA levels, in contrast to the swimmers, who showed a decrease in MDA levels and an increase in GSH/GSSG levels. Our findings suggest a differential shift in the KP and redox environment induced by diving and swimming. Swimming promotes an antioxidant environment and a peripheral overactivation of the KP.

Pomegranate and Its Components, Punicalagin and Ellagic Acid, Promote Antidepressant, Antioxidant, and Free Radical-Scavenging Activity in Ovariectomized Rats.

Previous reports described the antidepressant-like action of the aqueous extract of pomegranate (Punica granatum: AEPG). Thus we evaluated the effect of AEPG and the main compounds found in the extract, punicalagin (PNCG) and ellagic acid (EA), on forced swimming test and the redox environment (reactive oxygen species [ROS] production, lipoperoxidation [LPX], and cellular function) in the brain of rats treated with 3 weeks post ovariectomy exposed ex vivo to pro-oxidants. Also, we selected PNCG and EA to study their antidepressant-like effects (0.001, 0.01, 0.1, 1.0, and 10 mg/kg) in the forced swimming test and their scavenging capacities in chemical combinatorial assays (expressed as IC50 values). We observed a 2-fold increase in the formation of ROS and LPX in the brain after exposure to FeSO4. However, these effects were significantly attenuated when rats were treated with AEPG, PNCG, and EA (1 mg/kg and 0.010 mg/kg for 14 days). AEPG and EA significantly increased the cellular function values of brains that had been affected by the effect of FeSO4 and with ONOO-. PNCG and EA significantly reduced immobility behavior at the lower doses used in this study. The capacity of scavenging compounds to eliminate radicals was for hydroxyl radical (⋅OH), superoxide anion (O2⋅⁣-), and peroxynitrite (ONOO-) as follows: AEPG > punicalagin > ellagic acid. In conclusion, the AEPG and their active compounds PNCG and EA promote antidepressant-like actions and antioxidant activity as they attenuate oxidative damage and prevent cellular dysfunction in ovariectomized rat brains.

Cellular Localization of Kynurenine 3-Monooxygenase in the Brain: Challenging the Dogma.

Kynurenine 3-monooxygenase (KMO), a key player in the kynurenine pathway (KP) of tryptophan degradation, regulates the synthesis of the neuroactive metabolites 3-hydroxykynurenine (3-HK) and kynurenic acid (KYNA). KMO activity has been implicated in several major brain diseases including Huntington's disease (HD) and schizophrenia. In the brain, KMO is widely believed to be predominantly localized in microglial cells, but verification in vivo has not been provided so far. Here, we examined KP metabolism in the brain after depleting microglial cells pharmacologically with the colony stimulating factor 1 receptor inhibitor PLX5622. Young adult mice were fed PLX5622 for 21 days and were euthanized either on the next day or after receiving normal chow for an additional 21 days. Expression of microglial marker genes was dramatically reduced on day 22 but had fully recovered by day 43. In both groups, PLX5622 treatment failed to affect Kmo expression, KMO activity or tissue levels of 3-HK and KYNA in the brain. In a parallel experiment, PLX5622 treatment also did not reduce KMO activity, 3-HK and KYNA in the brain of R6/2 mice (a model of HD with activated microglia). Finally, using freshly isolated mouse cells ex vivo, we found KMO only in microglia and neurons but not in astrocytes. Taken together, these data unexpectedly revealed that neurons contain a large proportion of functional KMO in the adult mouse brain under both physiological and pathological conditions.

Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study.

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Kynurenine Monooxygenase Expression and Activity in Human Astrocytomas.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. The enzyme indoleamine-2,3-dioxygenase (IDO), which participates in the rate-limiting step of tryptophan catabolism through the kynurenine pathway (KP), is associated with poor prognosis in patients with GBM. The metabolites produced after tryptophan oxidation have immunomodulatory properties that can support the immunosuppressor environment. In this study, mRNA expression, protein expression, and activity of the enzyme kynurenine monooxygenase (KMO) were analyzed in GBM cell lines (A172, LN-18, U87, U373) and patient-derived astrocytoma samples. KMO mRNA expression was assessed by real-time RT-qPCR, KMO protein expression was evaluated by flow cytometry and immunofluorescence, and KMO activity was determined by quantifying 3-hydroxykynurenine by HPLC. Heterogenous patterns of both KMO expression and activity were observed among the GBM cell lines, with the A172 cell line showing the highest KMO expression and activity. Higher KMO mRNA expression was observed in glioma samples than in patients diagnosed with only a neurological disease; high KMO mRNA expression was also observed when using samples from patients with GBM in the TCGA program. The KMO protein expression was localized in GFAP+ cells in tumor tissue. These results suggest that KMO is a relevant target to be explored in glioma since it might play a role in supporting tumor metabolism and immune suppression.

Redox and Anti-Inflammatory Properties from Hop Components in Beer-Related to Neuroprotection.

Beer is a fermented beverage widely consumed worldwide with high nutritional and biological value due to its bioactive components. It has been described that both alcoholic and non-alcoholic beer have several nutrients derived from their ingredients including vitamins, minerals, proteins, carbohydrates, and antioxidants that make beer a potential functional supplement. Some of these compounds possess redox, anti-inflammatory and anticarcinogenic properties making the benefits of moderate beer consumption an attractive way to improve human health. Specifically, the hop cones used for beer brewing provide essential oils, bitter acids and flavonoids that are potent antioxidants and immune response modulators. This review focuses on the redox and anti-inflammatory properties of hop derivatives and summarizes the current knowledge of their neuroprotective effects.

Theoretical Insight into the Effect of Fluorine-Functionalized Metal-Organic Framework Supported Palladium Single-Site Catalyst in the Ethylene Dimerization Reaction.

Ethylene dimerization reaction is one of the most common mechanisms for the production of 1-butene. Recently, metal-organic frameworks (MOFs) have received extensive attention in this area since they combine all the advantages of homogeneous and heterogeneous catalysts in a single compound. Here a computational mechanistic study of MOF-supported palladium single-site catalyst for ethylene dimerization reaction is reported. Catalytic systems with both biphenyl-type backbone as organic ligand and its fluorine-functionalization have been investigated to reveal the origin of ligand effects on the catalytic activity and selectivity. The calculations revealed that the nonfluorinated palladium MOF catalyst undergoes dimerization over isomerization reaction. Then the influence of the fluorine-functionalized organic ligand was compared in the dimerization catalytic cycle, which was strongly favored in terms of activity and selectivity. Catalyst-substrate interactions were analyzed by energy decomposition analysis revealing the critical role of ligand backbone functionalization on the activity. This theoretical analysis identified three chemically meaningful dominant effects on these catalysts; steric, electrostatic and charge transfer effects. The steric effects promote nonfluorinated MOF catalyst, whereas the electrostatic effects are the dominant factor that promotes its fluorinated counterpart. This theoretical study provides feedback with future experimental studies about the role of fluorine ligand functionalization in palladium MOF catalysts for ethylene dimerization reaction.

Cognitive Impairment Induced by Lead Exposure during Lifespan: Mechanisms of Lead Neurotoxicity.

Lead (Pb) is considered a strong environmental toxin with human health repercussions. Due to its widespread use and the number of people potentially exposed to different sources of this heavy metal, Pb intoxication is recognized as a public health problem in many countries. Exposure to Pb can occur through ingestion, inhalation, dermal, and transplacental routes. The magnitude of its effects depends on several toxicity conditions: lead speciation, doses, time, and age of exposure, among others. It has been demonstrated that Pb exposure induces stronger effects during early life. The central nervous system is especially vulnerable to Pb toxicity; Pb exposure is linked to cognitive impairment, executive function alterations, abnormal social behavior, and fine motor control perturbations. This review aims to provide a general view of the cognitive consequences associated with Pb exposure during early life as well as during adulthood. Additionally, it describes the neurotoxic mechanisms associated with cognitive impairment induced by Pb, which include neurochemical, molecular, and morphological changes that jointly could have a synergic effect on the cognitive performance.

Subchronic N-acetylcysteine Treatment Decreases Brain Kynurenic Acid Levels and Improves Cognitive Performance in Mice.

The tryptophan (Trp) metabolite kynurenic acid (KYNA) is an α7-nicotinic and N-methyl-d-aspartate receptor antagonist. Elevated brain KYNA levels are commonly seen in psychiatric disorders and neurodegenerative diseases and may be related to cognitive impairments. Recently, we showed that N-acetylcysteine (NAC) inhibits kynurenine aminotransferase II (KAT II), KYNA's key biosynthetic enzyme, and reduces KYNA neosynthesis in rats in vivo. In this study, we examined if repeated systemic administration of NAC influences brain KYNA and cognitive performance in mice. Animals received NAC (100 mg/kg, i.p.) daily for 7 days. Redox markers, KYNA levels, and KAT II activity were determined in the brain. We also assessed the effect of repeated NAC treatment on Trp catabolism using brain tissue slices ex vivo. Finally, learning and memory was evaluated with and without an acute challenge with KYNA's bioprecursor L-kynurenine (Kyn; 100 mg/kg). Subchronic NAC administration protected against an acute pro-oxidant challenge, decreased KYNA levels, and lowered KAT II activity and improved memory both under basal conditions and after acute Kyn treatment. In tissue slices from these mice, KYNA neosynthesis from Trp or Kyn was reduced. Together, our data indicate that prolonged treatment with NAC may enhance memory at least in part by reducing brain KYNA levels.