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Novel benzophenone-thiazole hybrids with different substituents were synthesized and evaluated for anti-inflammatory activity using an ex vivo human whole-blood assay. All hybrids (3c and 5a-h) showed significant anti-inflammatory activity via prostaglandin E2 (PGE2) release inhibition. Moreover, 5c (82.8% of PGE2 inhibition), 5e (83.1% of PGE2 inhibition), and 5h (82.1% of PGE2 inhibition) were comparable to the reference drugs. Molecular docking revealed potential preferable binding to the active sites of cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) enzymes. This study provides the first evidence that benzophenone-thiazole hybrids may also dock in mPGES-1, a new attractive anti-inflammatory drug target, besides providing promising ex vivo anti-inflammatory activity. Thus, the novel hybrids are promising anti-inflammatory lead compounds and highlight the significance of optimal substituent selection in the design of potent PGE2 inhibitors., (© 2024 John Wiley & Sons Ltd.)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by diverse symptoms, where accurate diagnosis remains challenging. Traditional clinical observation methods often result in misdiagnosis, highlighting the need for biomarker-based diagnostic approaches. This study utilizes ultraperformance liquid chromatography coupled to an electrospray ionization source and quadrupole time-of-flight untargeted metabolomics combined with biochemometrics to identify novel serum biomarkers for PD. Analyzing a Brazilian cohort of serum samples from 39 PD patients and 15 healthy controls, we identified 15 metabolites significantly associated with PD, with 11 reported as potential biomarkers for the first time. Key disrupted metabolic pathways include caffeine metabolism, arachidonic acid metabolism, and primary bile acid biosynthesis. Our machine learning model demonstrated high accuracy, with the Rotation Forest boosting model achieving 94.1% accuracy in distinguishing PD patients from controls. It is based on three new PD biomarkers (downregulated: 1-lyso-2-arachidonoyl-phosphatidate and hypoxanthine and upregulated: ferulic acid) and surpasses the general 80% diagnostic accuracy obtained from initial clinical evaluations conducted by specialists. Besides, this machine learning model based on a decision tree allowed for visual and easy interpretability of affected metabolites in PD patients. These findings could improve the detection and monitoring of PD, paving the way for more precise diagnostics and therapeutic interventions. Our research emphasizes the critical role of metabolomics and machine learning in advancing our understanding of the chemical profile of neurodegenerative diseases.

The Croton genus (Euphorbiaceae) is recognized as a promising source for identifying bioactive compounds with antiproliferative activity. However, knowledge on the chemical composition and activity of Croton floribundus, Croton echinocarpus, and Croton zehntneri is limited. Thus, this study aimed to investigate the antiproliferative activity of these species on cells derived from tumoral breast, lung, and melanoma cells, and primary fibroblasts derived from human skin. Metabolomic strategies were applied via ultra-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to target the main active compound. The C. floribundus leaf extract exhibited the highest activity, with an IC 50 value lower than that of the reference drug - temozolomide - in the most responsive cell line - SK-MEL-147 - and in all the evaluated melanoma cell lines (SK-MEL-147, CHL-1 and WM-1366). Four tetrahydrofurofuran lignans were isolated for the first time from the most promising fraction of the C. floribundus extract. According to the metabolomic and multivariate statistical analyses, the isolated lignan epi-yangambin constituted the main antiproliferative compound against SK-MEL-147; furthermore, it exhibited selective antiproliferative activity for this cell line (IC 50  = 13.09 μg/mL and selectivity index = 3.82; temozolomide, IC 50  = 121.50 μg/mL) due to, at least in part, its ability to inhibit cell cycle progression at G2/M. This is especially relevant considering the high resistance of melanoma cells to available drugs. Thus, epi-yangambin can serve as a prototype for further antiproliferative investigations., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The Cissus gongylodes has traditionally been used in the diet of indigenous people in Brazil and in traditional medicine for kidney stone removal and inflammatory diseases. The active compounds responsible for these pharmacological activities are unknown., Aim of the Study: This study aims to isolate, for the first time, the compounds in the decoction of C. gongylodes leaves responsible for their anti-inflammatory and anti-urolithiatic ethnopharmacological properties., Materials and Methods: The most active fractions of the C. gongylodes leaf decoction were fractionated using SPE-C18 and the compounds were purified through HPLC-UV-DAD. The decoction fractions and isolated compounds were evaluated for their anti-inflammatory and anti-urolithiatic activities. The anti-inflammatory activity was assessed using an ex vivo assay in human blood induced by LPS and calcium ionophore, measuring inflammatory mediators, PGE2 and LTB4. The anti-urolithiatic activity was evaluated using an in vitro experimental model with human urine to determine the dissolution of the most recurrent calcium oxalate (CaOx) crystals. Additionally, the decoction was chemically characterized through metabolomic analysis using UHPLC-ESI-HRMS., Results: The isolated compounds from the decoction of C. gongylodes, including rutin, eriodictyol 3'-O-glycoside, and isoquercetin, have demonstrated significant multi-target actions. These components act as anti-inflammatory agents by inhibiting the release of main inflammatory mediators, PGE2 and LTB4. Additionally, they exhibit anti-urolithiatic properties, promoting the dissolution of calcium oxalate (CaOx) crystals. Furthermore, the characterization of the decoction by UHPLC-ESI-HRMS revealed a high content of flavonoids, mainly glycosylated flavonoids., Conclusions: The results support the traditional use of C. gongylodes decoction, identifying the compounds responsible for its anti-inflammatory and anti-urolithiatic effects. The decoction fractions and isolated compounds exhibited dual anti-inflammatory activity, effectively inhibiting key inflammatory pathways and potentially presenting fewer adverse effects while also promoting the dissolution of CaOx crystals associated with urolithiasis. The multi-target action displayed by C. gongylodes is particularly desirable in the treatment of urolithiasis, as inflammation and PGE2 production precede and contribute to the formation of CaOx crystals in the kidneys. Based on these actions, C. gongylodes emerges as a potent source of active compounds for the development of new treatments for urolithiasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We introduce a liquid chromatography - mass spectrometry with data-independent acquisition (LC-MS/DIA)-based strategy, specifically tailored to achieve comprehensive and reliable glycosylated flavonoid profiling. This approach facilitates in-depth and simultaneous exploration of all detected precursors and fragments during data processing, employing the widely-used open-source MZmine 3 software. It was applied to a dataset of six Ocotea plant species. This framework suggested 49 flavonoids potentially newly described for these plant species, alongside 45 known features within the genus. Flavonols kaempferol and quercetin, both exhibiting O -glycosylation patterns, were particularly prevalent. Gas-phase fragmentation reactions further supported these findings. For the first time, the apigenin flavone backbone was also annotated in most of the examined Ocotea species. Apigenin derivatives were found mainly in the C -glycoside form, with O. porosa displaying the highest flavone : flavonol ratio. The approach also allowed an unprecedented detection of kaempferol and quercetin in O. porosa species, and it has underscored the untapped potential of LC-MS/DIA data for broad and reliable flavonoid profiling. Our study annotated more than 50 flavonoid backbones in each species, surpassing the current literature., Competing Interests: There are no known conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Liquid chromatography coupled with high-resolution mass spectrometry data-independent acquisition (LC-HRMS/DIA), including MSE, enable comprehensive metabolomics analyses though they pose challenges for data processing with automatic annotation and molecular networking (MN) implementation. This motivated the present proposal, in which we introduce DIA-IntOpenStream, a new integrated workflow combining open-source software to streamline MSE data handling. It provides 'in-house' custom database construction, allows the conversion of raw MSE data to a universal format (.mzML) and leverages open software (MZmine 3 and MS-DIAL) all advantages for confident annotation and effective MN data interpretation. This pipeline significantly enhances the accessibility, reliability and reproducibility of complex MSE/DIA studies, overcoming previous limitations of proprietary software and non-universal MS data formats that restricted integrative analysis. We demonstrate the utility of DIA-IntOpenStream with two independent datasets: dataset 1 consists of new data from 60 plant extracts from the Ocotea genus; dataset 2 is a publicly available actinobacterial extract spiked with authentic standard for detailed comparative analysis with existing methods. This user-friendly pipeline enables broader adoption of cutting-edge MS tools and provides value to the scientific community. Overall, it holds promise for speeding up metabolite discoveries toward a more collaborative and open environment for research., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Species within the Ocotea genus (Lauraceae), have demonstrated an interesting profile of bioactivities. Renowned for their diverse morphology and intricate specialized metabolite composition, Ocotea species have re-emerged as compelling candidates for bioprospecting in drug discovery research. However, it is a genus insufficiently studied, particularly regarding anti-inflammatory activity., Purpose: To investigate the anti-inflammatory activity of Ocotea spp. extracts and determine the major markers in this genus., Methods: Extracts of 60 different Ocotea spp. were analysed by an ex vivo anti-inflammatory assay in human whole blood. The experiment estimates the prostaglandin E2 levels, which is one of the main mediators of the inflammatory cascade, responsible for the classical symptoms of fever, pain, and other common effects of the inflammatory process. Untargeted metabolomics analysis through liquid chromatography coupled with high-resolution mass spectrometry was performed, along with statistical analysis, to investigate which Ocotea metabolites are correlated with their anti-inflammatory activity., Results: The anti-inflammatory screening indicated that 49 out of 60 Ocotea spp. extracts exhibited significant inhibition of PGE2 release compared to the vehicle (p < 0.05). Furthermore, 10 of these extracts showed statistical similarity to the reference drugs. The bioactive markers were accurately identified using multivariate statistics combined with a fold change (> 1.5) and adjusted false discovery rate analysis as unknown compounds and alkaloids, with a majority of aporphine and benzylisoquinolines. These alkaloids were annotated with an increased level of confidence since MS E spectra were compared with comprehensive databases., Conclusion: This study represents the first bioprospecting report revealing the anti-inflammatory potential of several Ocotea spp. The determination of their anti-inflammatory markers could contribute to drug discovery and the chemical knowledge of the Ocotea genus., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Introduction: Similar to what it has been reported with preceding viral epidemics (such as MERS, SARS, or influenza), SARS-CoV-2 infection is also affecting the human immunometabolism with long-term consequences. Even with underreporting, an accumulated of almost 650 million people have been infected and 620 million recovered since the start of the pandemic; therefore, the impact of these long-term consequences in the world population could be significant. Recently, the World Health Organization recognized the post-COVID syndrome as a new entity, and guidelines are being established to manage and treat this new condition. However, there is still uncertainty about the molecular mechanisms behind the large number of symptoms reported worldwide. Aims and Methods: In this study we aimed to evaluate the clinical and lipidomic profiles (using non-targeted lipidomics) of recovered patients who had a mild and severe COVID-19 infection (acute phase, first epidemic wave); the assessment was made two years after the initial infection. Results: Fatigue (59%) and musculoskeletal (50%) symptoms as the most relevant and persistent. Functional analyses revealed that sterols, bile acids, isoprenoids, and fatty esters were the predicted metabolic pathways affected in both COVID-19 and post-COVID-19 patients. Principal Component Analysis showed differences between study groups. Several species of phosphatidylcholines and sphingomyelins were identified and expressed in higher levels in post-COVID-19 patients compared to controls. The paired analysis (comparing patients with an active infection and 2 years after recovery) show 170 dysregulated features. The relationship of such metabolic dysregulations with the clinical symptoms, point to the importance of developing diagnostic and therapeuthic markers based on cell signaling pathways., Competing Interests: MM and JV are employed by Waters Corporation. The remaining authors declare that the research was conducted in the absence of any commercial of financial relationships that could be seen as a potential conflict of interest., (Copyright © 2023 López-Hernández, Oropeza-Valdez, García Lopez, Borrego, Murgu, Valdez, López and Monárrez-Espino.)

Fenoterol is a sympathomimetic β2 receptor agonist primarily used as a bronchodilator. Due to its sympathomimetic actions, the World Anti-Doping Agency (WADA) has banned it. Multiple acute weight loss protocols (WLP) are used by Olympic athletes for sports that segregate athletes by weight; these generally involve caloric and water deprivation combined with heat exposure. Athletes use WLP before weigh-in, then transition to different body acute weight regain protocols (WRP) before competitions. Here, we studied the pharmacokinetics of fenoterol under WLP conditions: energetic dietary restriction, decreased water intake, and exposure to a dry sauna (80 ± 2 °C), followed by a WRP. Five elite-level female judo athletes participated in the study. Four received fenoterol (200 μg; n = 2 or 400 μg; n = 2), while one was a control receiving placebo under identical conditions. We measured excretion of the fenoterol parent molecule and presented qualitative data of its sulfated metabolite using QqQ tandem quadrupole mass spectrometry for 118 h. The fenoterol parent appeared earlier in urine than did its conjugated metabolite; excretion profiles were similar among all subjects. The centers of mass for fenoterol parent curves were (time, fenoterol): athlete A (10.9, 7.3); athlete B (9.2, 27.3); athlete C (8.5, 6.9); athlete D (9.7, 5.0). After initiating WRP, we observed a burst in urinary fenoterol excretion once in complete decay. This trend was observed for all four athletes who received fenoterol. Our results suggest that during hypohydration, some of the unmetabolized fenoterol accumulates in tissues, then is released during rehydration. These findings can be important for detecting fenoterol use in athletes., Competing Interests: Declaration of Competing Interest JA and BA-N are attorneys. LCC is a biochemistry consultant for doping cases., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hops (Humulus lupulus L.) are edible flowers commonly used to add flavour and aroma to beer, besides they have rich chemical diversity and medicinal potential. In this work, an ex vivo anti-inflammatory assay via the LPS-induced signalling pathway and metabolomics approaches were performed to evaluate the ability of hops to inhibit the production of prostaglandin E2 (PGE2) inflammatory mediator and analyze which metabolites produced by the nine different hop cultivars are potential anti-inflammatory markers. Columbus, Chinook and Hallertau Mittelfrüh hop cultivars yielded extracts with PGE2 release inhibition rates of 86.7, 92.5 and 73.5 %, respectively. According to the multivariate statistical analysis, the majority of the metabolites correlated with the activity were prenylated phloroglucinol and phenolic homologs. These results suggest promissory anti-inflammatory hop metabolites., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Introduction: Plants have been considered a promising source for discovering new compounds with pharmacological activities. The Fabaceae family comprises a large variety of species that produce substances with diverse therapeutic potential, including anti-inflammatory activity. The limitations of current anti-inflammatories generate the need to research new anti-inflammatory structures with higher efficacy as well as develop methods for screening multiple samples, reliably and ethically, to assess such therapeutic properties., Objective: Validate and apply a quantification method for prostaglandin E 2 (PGE 2 ) production from an ex vivo assay in human blood in order to screen anti-inflammatory activity present in many Fabaceae species extracts., Methods: Human blood was incubated with extracts from 47 Fabaceae species. After lipopolysaccharide (LPS)-induced inflammation, PGE 2 was quantified in the plasma by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The extracts that presented PGE 2 production inhibition were further assessed through in vivo assay and then chemically characterised through an analysis of ultra-performance liquid chromatography electrospray ionisation quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-QTOF-MS 2 ) data., Results: The new ex vivo anti-inflammatory assay showed that five out of the 47 Fabaceae species inhibited PGE 2 production. Results from an in vivo assay and the metabolic profile of the active extracts supported the anti-inflammatory potential of four species., Conclusion: The quantification method for PGE 2 demonstrated fast, sensitive, precise, and accurate results. The new ex vivo anti-inflammatory assay comprised a great, reliable, and ethical approach for the screening of a large number of samples before an in vivo bioassay. Additionally, the four active extracts in both ex vivo and in vivo assays may be useful for the development of more efficient anti-inflammatory drugs., (© 2021 John Wiley & Sons, Ltd.)

Atypical antipsychotics are widely used to manage schizophrenia symptoms. However, these drugs can induce deleterious side effects, such as MetS, which are associated with an increased cardiovascular risk to patients. Lipids play a central role in this context, and changes in lipid metabolism have been implicated in schizophrenia's pathobiology. Furthermore, recent evidence suggests that lipidome changes may be related to antipsychotic treatment response. The aim of this study was to evaluate the lipidome changes in blood plasma samples of schizophrenia patients before and after 6 weeks of treatment with either risperidone, olanzapine, or quetiapine. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis showed changes in the levels of ceramides (Cer), glycerophosphatidic acids (PA), glycerophosphocholines (PC), phosphatidylethanolamines (PE), phosphatidylinositols (PI), glycerophosphoglycerols (PG), and phosphatidylserines (PS) for all treatments. However, the treatment with risperidone also affected diacylglycerides (DG), ceramide 1-phosphates (CerP), triglycerides (TG), sphingomyelins (SM), and ceramide phosphoinositols (PI-Cer). Moreover, specific lipid profiles were observed that could be used to distinguish poor and good responders to the different antipsychotics. As such, further work in this area may lead to lipid-based biomarkers that could be used to improve the clinical management of schizophrenia patients., Competing Interests: Declaration of Competing Interest “The authors have declared no conflict of interest”., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In this era of precision medicine, there is an increasingly urgent need for highly sensitive tests for detecting tumors such as colon cancer (CC), a silent disease where the first symptoms may take 10-15 years to appear. Mass spectrometry-based lipidomics is an emerging tool for such clinical diagnosis. We used ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry operating in high energy collision spectral acquisition mode (MS E ) mode (UPLC-QTOF-MS E ) and gas chromatography (GC) to investigate differences between the plasmatic lipidic composition of CC patients and control (CTR) subjects. Key enzymes in lipidic metabolism were investigated using immuno-based detection assays. Our partial least squares discriminant analysis (PLS-DA) resulted in a suitable discrimination between CTR and CC plasma samples. Forty-two statistically significant discriminating lipids were putatively identified. Ether lipids showed a prominent presence and accordingly, a decrease in glyceronephosphate O-acyltransferase (GNPAT) enzyme activity was found. A receiver operating characteristic (ROC) curve built for three plasmalogens of phosphatidylserine (PS), named PS(P-36:1), PS(P-38:3) and PS(P-40:5), presented an area under the curve (AUC) of 0.998, and sensitivity and specificity of 100 and 85.7% respectively. These results show significant differences in CC patients' plasma lipid composition that may be useful in discriminating them from CTR individuals with a special role for plasmalogens.

Ethnopharmacology Relevance: Ayahuasca is a tea produced through decoction of Amazonian plants. It has been used for centuries by indigenous people of South America. The beverage is considered to be an ethnomedicine, and it is traditionally used for the treatment of a wide range of diseases, including neurological illness. Besides, some scientific evidence suggests it may be applicable to Parkinson's disease (PD) treatment. Thus, Ayahuasca deserves in depth studies to clarify its potential role in this disease., Aim of the Study: This study aimed to use an untargeted metabolomics approach to evaluate the neuroprotective potential of the Ayahuasca beverage, the extracts from its matrix plants (Banisteriopsis caapi and Psychotria viridis), its fractions and its main alkaloids on the viability of SH-SY5Y neuroblastoma cells in an in vitro PD model., Material and Methods: The cytotoxicity of Ayahuasca, crude extracts, and fractions of B. caapi and P. viridis, as well as neuroprotection promoted by these samples in a 6-hydroxydopamine (6-OHDA)-induced neurodegeneration model, were evaluated by the MTT assay at two time-points: 48 h (T1) and 72 h (T2). The main alkaloids from Ayahuasca matrix plants, harmine (HRE) and N,N-dimethyltryptamine (DMT), were also isolated and evaluated. An untargeted metabolomics approach was developed to explore the chemical composition of samples with neuroprotective activity. Ultra-Performance Liquid Chromatography coupled to Electrospray Ionisation and Time-of-Flight (UPLC-ESI-TOF) metabolome data was treated and further analysed using multivariate statistical analyses (MSA): principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The metabolites were dereplicated using the Dictionary of Natural Products and an in house database. The main alkaloids were also quantified by UPLC-MS/MS., Results: The samples did not cause cytotoxicity in vitro and three of samples intensely increased cell viability at T1. The crude extracts, alkaloid fractions and HRE demonstrated remarkable neuroprotective effect at T2 while the hydroalcoholic fractions demonstrated this neuroprotective effect at T1 and T2. Several compounds from different classes, such as β-carbolines and monoterpene indole alkaloids (MIAs) were revealed correlated with this property by MSA. Additionally, a total of 2419 compounds were detected in both ionisation modes. HRE showed potent neuroprotective action at 72 h, but it was not among the metabolites positively correlated with the most efficacious neuroprotective profile at either time (T1 and T2). Furthermore, DMT was statistically important to differentiate the dataset (VIP value > 1), although it did not exhibit sufficient neuroprotective activity by in vitro assay, neither a positive correlation with T1 and T2 neuroprotective profile, which corroborated the MSA results., Conclusion: The lower doses of the active samples stimulated neuronal cell proliferation and/or displayed the most efficacious neuroprotection profile, namely by preventing neuronal damage and improving cell viability against 6-OHDA-induced toxicity. Intriguingly, the hydroalcoholic fractions exhibited enhanced neuroprotective effects when compared to other samples and isolated alkaloids. This finding corroborates the significance of a holistic approach. The results demonstrate that Ayahuasca and its base plants have potential applicability for PD treatment and to prevent its progression differently from current drugs to treat PD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Plasma and tissue from breast cancer patients are valuable for diagnostic/prognostic purposes and are accessible by multiple mass spectrometry (MS) tools. Liquid chromatography-mass spectrometry (LC-MS) and ambient mass spectrometry imaging (MSI) were shown to be robust and reproducible technologies for breast cancer diagnosis. Here, we investigated whether there is a correspondence between lipid cancer features observed by desorption electrospray ionization (DESI)-MSI in tissue and those detected by LC-MS in plasma samples. The study included 28 tissues and 20 plasma samples from 24 women with ductal breast carcinomas of both special and no special type (NST) along with 22 plasma samples from healthy women. The comparison of plasma and tissue lipid signatures revealed that each one of the studied matrices (i.e., blood or tumor) has its own specific molecular signature and the full interposition of their discriminant ions is not possible. This comparison also revealed that the molecular indicators of tissue injury, characteristic of the breast cancer tissue profile obtained by DESI-MSI, do not persist as cancer discriminators in peripheral blood even though some of them could be found in plasma samples.

The limited access to functional human brain tissue has led to the development of stem cell-based alternative models. The differentiation of human pluripotent stem cells into cerebral organoids with self-organized architecture has created novel opportunities to study the early stages of the human cerebral formation. Here we applied state-of-the-art label-free shotgun proteomics to compare the proteome of stem cell-derived cerebral organoids to the human fetal brain. We identified 3,073 proteins associated with different developmental stages, from neural progenitors to neurons, astrocytes, or oligodendrocytes. The major protein groups are associated with neurogenesis, axon guidance, synaptogenesis, and cortical brain development. Glial cell proteins related to cell growth and maintenance, energy metabolism, cell communication, and signaling were also described. Our data support the variety of cells and neural network functional pathways observed within cell-derived cerebral organoids, confirming their usefulness as an alternative model. The characterization of brain organoid proteome is key to explore, in a dish, atypical and disrupted processes during brain development or neurodevelopmental, neurodegenerative, and neuropsychiatric diseases., (Copyright © 2019 Nascimento, Saia-Cereda, Sartore, Madeiro da Costa, Schitine, Freitas, Murgu, de Melo Reis, Rehen and Martins-de-Souza.)

Chronic exposure to arsenic (As), whether directly through the consumption of contaminated drinking water or indirectly through the daily intake of As-contaminated food, is a health threat for more than 150 million people worldwide. Epidemiological studies found an association between chronic consumption of As and several pathologies, the most common being cancer-related disorders. However, As consumption has also been associated with metabolic disorders that could lead to diverse pathologies, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease, and obesity. Here, we used ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization/quadrupole time-of-flight mass spectrometry (ESI-QToF) to assess the effect of chronic intergenerational As exposure on the lipid metabolism profiles of serum from 4-month-old Wistar rats exposed to As prenatally and also during early life in drinking water (3 ppm). Significant differences in the levels of certain identified lysophospholipids, phosphatidylcholines, and triglycerides were found between the exposed rats and the control groups, as well as between the sexes. Significantly increased lipid oxidation determined by the malondialdehyde (MDA) method was found in exposed rats compared with controls. Chronic intergenerational As exposure alters the rat lipidome, increases lipid oxidation, and dysregulates metabolic pathways, the factors associated with the chronic inflammation present in different diseases associated with chronic exposure to As (i.e., keratosis, Bowen's disease, and kidney, liver, bladder, and lung cancer)., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Cesar Rivas-Santiago et al.)

Gestational diabetes mellitus (GDM) is a disorder in pregnancy with highest impact in the future life of both mother and newborn. Increasing incidence, economic impact, and potential for severe GDM-related pregnancy complications are some factors that have motivated the deep study of physiopathology, risk factors for developing GDM, and potential biomarkers for its diagnosis. In the present pilot study, we analyzed the urinary metabolome profile of GDM patients in the 3rd trimester of pregnancy, when GDM is already established and the patients are under dietary and pharmacological control. An untargeted metabolomics method based on liquid chromatography⁻mass spectrometry analysis was developed to identify differentially expressed metabolites in the GDM group. We identified 14 metabolites that are significantly upregulated in the urine of GDM patients, and, more importantly, we identified those related with the steroid hormone biosynthesis and tryptophan (TRP) metabolism pathways, which are associated with GDM pathophysiology. Thus, these metabolites could be screened as potential prognostic biomarkers of type two diabetes mellitus, coronary artery disease and chronic renal failure in future follow-up studies with GDM patients.

Type-2 Diabetes (T2D) is a predisposing cause for developing tuberculosis (TB) in low- and middle-income countries. TB-T2D comorbidity worsens clinical control and prognosis of the affected individuals. The underlying metabolic alterations for this infectious-metabolic disease are still largely unknown. Possible mediators of the increased susceptibility to TB in diabetic patients are lipids levels, which are altered in individuals with T2D. To evaluate the modulation of glycerophospholipids in patients with TB-T2D, an untargeted lipidomic approach was developed by means of ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization/quadrupole time-of-flight mass spectrometry (ESI-QToF). In addition, tandem mass spectrometry was performed to determine the identity of the differentially expressed metabolites. We found that TB infected individuals with or without T2D share a common glycerophospholipid profile characterized by a decrease in phosphatidylcholines. A total of 14 glycerophospholipids were differentially deregulated in TB and TB-T2D patients and could potentially be considered biomarkers. It is necessary to further validate these identified lipids as biomarkers, focusing on the anticipate diagnosis for TB development in T2D predisposed individuals., (Copyright © 2019 IMSS. Published by Elsevier Inc. All rights reserved.)

This is the first study to identify lipidomic markers in plasma associated with response of acutely ill schizophrenia patients in response to specific antipsychotic treatments. The study population included 54 schizophrenia patients treated with antipsychotics for 6 weeks. Treatment led to significant improvement in positive and negative symptoms for 34 patients with little or no improvement for 20 patients. In addition, 37 patients showed an increase in body mass index after the 6 week treatment period, consistent with effects on metabolism and the association of such effects with symptom improvement. Profiling of plasma samples taken prior to therapy using liquid chromatography tandem mass spectrometry (LC-MS/MS) resulted in identification of 38, 10, and 52 compounds associated with the olanzapine, risperidone, and quetiapine treatment groups, which could be used to distinguish responders from non-responders. Limitations include the retroactive active nature of the study and the small sample size. Further investigations with larger sample sets could lead to the development of a molecular test that could be used to help psychiatrists determine the best treatment options for each patient.

Atmospheric solids analysis probe mass spectrometry (ASAP-MS) is a powerful tool for analysis of solid and liquid samples. It is an excellent alternative for crude oil analysis without any sample preparation step. Here, ASAP-MS in positive ion mode, ASAP(+)-MS, has been optimized for analysis of condensed aromatics (CA) standards, crude oil, and paraffinic fraction samples using a Synapt G2-S HDMS. Initially, two methodologies were used to access the chemical composition of samples: (1) using a temperature gradient varying from 150 to 600 °C at a heating rate of 150 °C min -1 , and (2) with constant temperature of 300 and 400 °C. ASAP(+)-MS ionized many compounds with a typical petroleum profile, showing a greater signals range of m/z 250-1300 and 200-1400 for crude oil and paraffin samples, respectively. Such performance, mainly related to the detection of high molecular weight compounds (>1000 Da), is superior to that of other traditional ionization sources, such as ESI, APCI, DART, and DESI. Additionally, the CA standards were identified in both forms: radicals, [M] +• , and protonated cations, [M + H] + , with minimum fragmentation. Therefore, ASAP was more efficient in accessing the chemical composition of nonpolar and polar compounds. It is promising in its application with ultrahigh resolution MS instruments, such as FT-ICR MS and Orbitrap, since molecular formulas with greater resolution and mass accuracy (<1 ppm) would be assigned. Graphical Abstract ᅟ.

It is highly desirable to screen for a large variety of organic compounds in water. Ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) can analyse semi-polar to polar organic compounds in tap and mineral water. The use of UHPLC-HRMS is well consolidated for lipidomic, metabolomic and proteomic studies; based on the detection of a very large number of compounds of a variety of organic functions. Water analysis is usually performed by gas chromatography -mass spectrometry (GC-MS) techniques that are efficient for volatile organic compounds. Therefore the use of UHPLC-HRMS as a screening method based on an untargeted omic approach for the analysis of organic compounds with polar functional groups is welcome. This UHPLC-HRMS method was developed and tested with tap water and mineral water. We analysed six different brands of mineral water from France, Spain, Norway and Brazil and tap water from Jandaia do Sul, PR, Brazil to test the approach and demonstrate how UHPLC-HRMS may be used as a screening method for water quality. Forty-seven different ions were observed in tap and mineral water and their intensities were submitted to principal component analysis (PCA) evaluation. Fifteen ions were identified comparing the mass spectrometric results to metabolomic and lipidomic libraries., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Docosahexaenoic acid (DHA) is an n-3 polyunsaturated fatty acid that is highly enriched in the brain, and the oxidation products of DHA are present or increased during neurodegenerative disease progression. The characterization of the oxidation products of DHA is critical to understanding the roles that these products play in the development of such diseases. In this study, we developed a sensitive and specific analytical tool for the detection and quantification of twelve major DHA hydroperoxide (HpDoHE) and hydroxide (HDoHE) isomers (isomers at positions 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, 19 and 20) in biological systems. In this study, HpDoHE were synthesized by photooxidation, and the corresponding hydroxides were obtained by reduction with NaBH4. The isolated isomers were characterized by LC-MS/MS, and unique and specific fragment ions were chosen to construct a selected reaction monitoring (SRM) method for the targeted quantitative analysis of each HpDoHE and HDoHE isomer. The detection limits for the LC-MS/MS-SRM assay were 1-670 pg for HpDoHE and 0.5-8.5 pg for HDoHE injected onto a column. Using this method, it was possible to detect the basal levels of HDoHE isomers in both rat plasma and brain samples. Therefore, the developed LC-MS/MS-SRM can be used as an important tool to identify and quantify the hydro(pero)xy derivatives of DHA in biological system and may be helpful for the oxidative lipidomic studies.

The synthesis, structure, and hydrolase-like catalytic activity of a new mononuclear gadolinium complex [Gd(L)(NO3)(H2O)3](NO3)2 (1) are reported. A clean two-stage kinetic reaction for hydrolysis of the diester 2,4-bis(dinitrophenyl)phosphate by 1 was followed, and the rate constants were determined. A high DNA cleavage activity was also demonstrated. The active species in the hydrolytic process is proposed based on the X-ray structure, electrospray ionization mass spectrometry analysis, and kinetic and potentiometric equilibrium studies of 1.