Characterization and Quantification of Naphthenic Acids in Produced Water by Orbitrap MS and a Multivariate Approach.

Naphthenic acids (NAs) naturally occur in crude oil and its associated produced water, presenting significant challenges, such as corrosion, in refinery apparatus and ecotoxicity in aquatic habitats. This study delineates a multivariate method to quantify NAs in produced water via electrospray ionization coupled with high-resolution Orbitrap mass spectrometry (ESI-Orbitrap MS). By employing liquid-liquid extraction, followed by direct infusion ESI(-)-Orbitrap MS, we characterized and quantified NAs employing a partial least-squares regression (PLS) model enhanced by the ordered predictor selection (OPS) algorithm. Thirty-six produced water samples were utilized, with 24 allocated for calibration and 12 designated for validation. The PLS-OPS model demonstrated notable accuracy in predicting NA concentrations in simulated and actual produced water samples ranging from ∼30 to 300 mg·L-1. This methodology offers a rapid yet robust alternative for quantifying NAs using mass spectrometry augmented by PLS and the OPS. Its significance is underscored by its potential to equip the petroleum industry with a swift and reliable monitoring mechanism for NAs in produced water, thereby aiding in mitigating environmental and operational risks.

A novel arylpiperazine derivative (LQFM181) protects against neurotoxicity induced by 3- nitropropionic acid in in vitro and in vivo models.

In the pursuit of novel antioxidant therapies for the prevention and treatment of neurodegenerative diseases, three new arylpiperazine derivatives (LQFM181, LQFM276, and LQFM277) were synthesized through a molecular hybridization approach involving piribedil and butylated hydroxytoluene lead compounds. To evaluate the antioxidant and neuroprotective activities of the arylpiperazine derivatives, we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (neurotoxicity induced by 3-nitropropionic acid in Swiss mice) models. In the in vitro tests, LQFM181 showed the most promising antioxidant activity at the neuronal membrane and cytoplasmic levels, and significant neuroprotective activity against the neurotoxicity induced by 3-nitropropionic acid. Hence, this compound was further subjected to in vivo evaluation, which demonstrated remarkable antioxidant capacity such as reduction of MDA and carbonyl protein levels, increased activities of succinate dehydrogenase, catalase, and superoxide dismutase. Interestingly, using the same in vivo model, LQFM181 also reduced locomotor behavior and memory dysfunction through its ability to decrease cholinesterase activity. Consequently, LQFM181 emerges as a promising candidate for further investigation into its neuroprotective potential, positioning it as a new therapeutic agent for neuroprotection.

Integrated Metabolic and Inflammatory Signatures Associated with Severity of, Fatality of, and Recovery from COVID-19.

Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19. IMPORTANCE COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.

Anxiolytic- and antidepressant-like effects of new phenylpiperazine derivative LQFM005 and its hydroxylated metabolite in mice.

The current treatments available for anxiety and depression are only palliative. Full remission has remained elusive, characterizing unmet medical needs. In the scope of an academic drug discovery program, we describe here the design, synthesis, in vitro metabolism prediction and pharmacological characterization of a new piperazine compound, 1-(4-methoxyphenyl)-4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazine (LQFM005), and of its main putative metabolite, 4-(4-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)- 1H-pyrazol-1-yl)phenol (LQFM235). The production of the metabolite was initially performed by in vitro biotransformation of LQFM005 using Aspergillus candidus and then by chemical synthesis. Oral administration of either 12 or 24 µmol/kg LQFM005 to mice did not affect spontaneous locomotor activity but increased the time spent in the center of the open field. Both LQFM005 and LQFM235 (24 µmol/kg) increased the time spent by the mice in the open arms of the elevated plus maze (EPM), a good indication of anxiolytic-like effect, and decreased the immobility time in the forced swimming test (FST), suggesting an antidepressant-like effect. The previous administration of WAY-100635 (a 5-HT1A antagonist) abolished the effects of LQFM005 in both EPM and FST. Binding experiments showed that LQFM005 and its metabolite bind to the 5-HT1A receptor with a moderate affinity (Ki around 5-9 µM). The two compounds are relatively safe, as indicated by cytotoxic assessment using the 3T3 fibroblast cell line and estimated LD50 around 600 mg/kg. In conclusion, oral administration of the newly synthesized phenylpiperazines produced anxiolytic- and antidepressant-like effects in behavioral tests, putatively in part through the activation of 5-HT1A receptors.

A New Strategy for the Analysis of Steroid Hormones in Industrial Wastewaters by Paper Spray Ionization Mass Spectrometry.

A new approach using paper spray ionization mass spectrometry (PSI-MS) for the analysis of steroid hormones in wastewater samples has been demonstrated. Triangular papers containing paraffin barriers as microfluidic channels were used to direct the sample solution to the paper tip, preventing the sample from spreading over the corners of the paper. The method was used to analyze the hormones levonorgestrel and algestone acetophenide in industrial wastewaters. Analytical curves presented a correlation coefficient (R2) above 0.99. Limits of quantification were below 2.3 ppm and limits of detection below 0.7 ppm. Values of precision (coefficient of variation) and accuracy (relative error) were less than 15% for all analyses. Recovery results ranged from 82% to 102%. Levonorgestrel was also analyzed by high-performance liquid chromatography coupled to mass spectrometry in order to compare the analytical performance with PSI-MS. No statistically significant differences were found between both methods. This study demonstrates the usefulness of PSI-MS for rapid analysis of hormones in industrial wastewater samples and also indicates its potential to be employed as a simple and reliable analytical method in environmental sciences.

Chemical characterization and pharmacological assessment of polysaccharide free, standardized cashew gum extract (Anacardium occidentale L.).

ETHNOPHARMACOLOGICAL RELEVANCE: The cashew gum (Anacardium occidentale L.) is used in traditional Brazilian medicine in the treatment of inflammatory conditions, asthma, diabetes, and gastrointestinal disturbances. AIM OF THE STUDY: In the present study, we aimed at forming a chemical characterization and investigation of the antinociceptive and anti-inflammatory activities of the aqueous extract of cashew gum without the presence of polysaccharides in its composition (CGE). MATERIALS AND METHODS: The CGE was obtained after the precipitation and removal of polysaccharides through the use of acetone. After, the acetone was removed by rotaevaporation, and the concentrated extract was lyophilized. The chemical characterization of CGE was performed by liquid chromatography mass spectrometry (LC-MS) and tandem mass spectrometry (MS/MS) analyses. Mice were used for the evaluation of the antinociceptive and anti-inflammatory activities. CGE was analyzed via the Irwin test, acetic acid-induced writhing test, formalin-induced pain test, and carrageenan-induced paw edema test. The motor activity or probable sedation was verified through the chimney, open-field, and sodium pentobarbital-induced sleep tests. We investigated if the analgesic and anti-inflammatory effects of CGE depend of reduction in PGE2 levels, were performed the carrageenan or PGE2-induced hyperalgesia tests. RESULTS: The chemical characterization of CGE showed the presence of anacardic acids as the predominant phytoconstituents. The treatment with CGE (75, 150, and 300mg/kg, p.o.) inhibited the number of writhing in a dose-dependent manner. With an intermediate dose, CGE did not cause motor impairment with the chimney test or alterations in either the open-field or sodium pentobarbital-induced sleep. In the formalin-induced pain test, CGE (150mg/kg, p.o.) produced an antinociceptive effect only in the first phase of the test, suggesting anti-inflammatory activity. With the same dosage, CGE also reduced the carrageenan-induced paw edema at all hours of the test, confirming its anti-inflammatory effect. Furthermore, CGE (150mg/kg, p.o.) presented an antihyperalgic effect at all hours of the carrageenan-induced hyperalgesia test. However, this dose of CGE was not able to reduce the hyperalgesia induced by PGE2, suggesting that the anti-inflammatory effect of this extract depends on the reduction in the PGE2 levels. CONCLUSION: The anacardic acids are the predominant phytoconstituents identified in the CGE. The action mechanisms of CGE suggest the reduction in the PGE2 levels. These findings support the use of cashew gum in popular medicine and demonstrate that part of its antinociceptive and anti-inflammatory effects should also be attributed to the presence of anacardic acids in its composition, independent of the presence of polysaccharides.

Molecularly imprinted polymer (MIP) membrane assisted direct spray ionization mass spectrometry for agrochemicals screening in foodstuffs.

Paper spray ionization (PSI) has some limitations such as low sensitivity and ionization suppression when complex samples are analyzed. The use of sample preparation devices directly coupled to MS can avoid these restrictions. Molecularly imprinted polymers (MIPs) are materials widely used as adsorbent in sample preparation methods such as solid-phase extraction and solid-phase microextraction, and they can provide specifics cavities with affinity to a target molecule. Here, we introduce a new MIP membrane spray ionization method combining MIP and PSI. MIP was synthesized directly on a cellulose membrane. Monuron and 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) were used as template molecules in MIP synthesis for diuron and 2,4-D (2,4-dichlorophenoxyacetic acid) analyte sequesters, respectively. Apple, banana and grape methanolic extracts were used as matrices. The MIP membrane spray showed signal intensities of diuron and 2,4-D that were much higher compared to those obtained by non-imprinted polymers(NIP). Calibration curves exhibited R2 > 0.99 for diuron and 2,4-D in all fruit extracts analyzed. LODs were found less than 0.60µgL-1 and LLOQs were found less than 2.00µgL-1. The coefficients of variation and relative errors were less than 15% for almost all analyses. The apparent recovery test results ranged between 92,5% and 116.9%. Finally, the MIP membrane spray method was employed for the quantification of diuron and 2,4-D in real samples. Diuron contents were only found in three bananas (4.0, 6.5, and 9.9µgL-1). The proposed MIP membrane spray ionization method was straightforward, fast to carry out and provided satisfactory results for analyses of diuron and 2,4-D in apple, banana and grape samples.