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1. Targeted and untargeted urinary metabolic profiling of bladder cancer

   https://doi.org/10.1016/j.jpba.2023.115473  

   Ossoliński, Krzysztof; Ruman, Tomasz; Copié, Valérie; Tripet, Brian P.; Kołodziej, Artur; Płaza-Altamer, Aneta; Ossolińska, Anna; Ossoliński, Tadeusz; Nieczaj, Anna; Nizioł, Joanna (May 2023, Journal of Pharmaceutical and Biomedical Analysis)

   Bladder cancer (BC) is frequent cancer affecting the urinary tract and is one of the most prevalent malignancies worldwide. No biomarkers that can be used for effective monitoring of therapeutic interventions for this cancer have been identified to date. This study investigated polar metabolite profiles in urine samples from 100 BC patients and 100 normal controls (NCs) using nuclear magnetic resonance (NMR) and two methods of high- resolution nanoparticle-based laser desorption/ionization mass spectrometry (LDI-MS). Five urine metabolites were identified and quantified using NMR spectroscopy to be potential indicators of bladder cancer. Twenty-five LDI-MS-detected compounds, predominantly peptides and lipids, distinguished urine samples from BC and NCs individuals. Level changes of three characteristic urine metabolites enabled BC tumor grades to be distinguished, and ten metabolites were reported to correlate with tumor stages. Receiver-Operating Characteristics analysis showed high predictive power for all three types of metabolomics data, with the area under the curve (AUC) values greater than 0.87. These findings suggest that metabolite markers identified in this study may be useful for the non-invasive detection and monitoring of bladder cancer stages and grades. 

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2. Silencing of the Transmembrane Transporter (swnT) Gene of the Fungus Slafractonia leguminicola Results in a Reduction of Mycotoxin Transport

   https://doi.org/10.3390/jof9030370  

   Das, Sumanjari; Gardner, Dale R.; Neyaz, Marwa; Charleston, Allen B.; Cook, Daniel; Creamer, Rebecca (March 2023, Journal of Fungi)

   Slafractonia leguminicola infects red clover and other legumes, causing black patch disease. This pathogenic fungus also produces two mycotoxins, slaframine and swainsonine, that are toxic to livestock grazing on clover hay or pasture infested with S. leguminicola. Swainsonine toxicosis causes locoism, while slaframine causes slobbers syndrome. The mechanism of toxin secretion by S. leguminicola is poorly understood. The aim of this research was to investigate the role of a putative transmembrane transporter, SwnT, in mycotoxin transport. The swnT gene was silenced by RNA interference using the silencing vector Psilent1, which included inverted repeat transgenes of swnT. This resulted in a significant reduction of swnT transcript levels compared with the controls. Silencing caused a decline in the active efflux of toxins from the mycelia to the media, as shown by LC–MS analysis. Transformants in which swnT was silenced showed higher concentrations of both toxins in the mycelia compared with the concentrations in the media. These transformants exhibited a visibly distinct phenotype with much thicker and shorter mycelia than in the wild type. These transformants were also unable to infect detached clover leaves, unlike the controls, suggesting that SwnT function may play an important role in pathogenesis in addition to mycotoxin transport. This research demonstrates the importance of this transporter to the secretion of mycotoxins for this phytopathogenic fungus. 

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3. Metabolomic and elemental profiling of blood serum in bladder cancer

   https://doi.org/10.1016/j.jpha.2022.08.004  

   Ossoliński, Krzysztof; Ruman, Tomasz; Copié, Valérie; Tripet, Brian P.; Nogueira, Leonardo B.; Nogueira, Katiane O.P.C.; Kołodziej, Artur; Płaza-Altamer, Aneta; Ossolińska, Anna; Ossoliński, Tadeusz; et al (September 2022, Journal of Pharmaceutical Analysis)

   Bladder cancer (BC) is one of the most frequently diagnosed types of urinary cancer. Despite advances in treatment methods, no specific biomarkers are currently in use. Targeted and untargeted profiling of metabolites and elements of human blood serum from 100 BC patients and the same number of normal controls (NCs), with external validation, was attempted using three analytical methods, i.e., nuclear magnetic resonance, gold and silver-109 nanoparticle-based laser desorption/ionization mass spec- trometry (LDI-MS), and inductively coupled plasma optical emission spectrometry (ICP-OES). All results were subjected to multivariate statistical analysis. Four potential serum biomarkers of BC, namely, iso- butyrate, pyroglutamate, choline, and acetate, were quantified with proton nuclear magnetic resonance, which had excellent predictive ability as judged by the area under the curve (AUC) value of 0.999. Two elements, Li and Fe, were also found to distinguish between cancer and control samples, as judged from ICP-OES data and AUC of 0.807 (in validation set). Twenty-five putatively identified compounds, mostly related to glycans and lipids, differentiated BC from NCs, as detected using LDI-MS. Five serum metab- olites were found to discriminate between tumor grades and nine metabolites between tumor stages. The results from three different analytical platforms demonstrate that the identified distinct serum metabolites and metal elements have potential to be used for noninvasive detection, staging, and grading of BC. 

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4. Noninvasively Monitoring Orangutan Health Status: Determining Urine Concentrations

   Malbouf, Bryanna; Kane, Erin E; L Durgavich, Lara; Knott, Cheryl D (November 2019, Fifth Annual Meeting of the Northeastern Evolutionary Primatologists)

   Biomarkers including reproductive hormones and indicators of energy balance can be used to analyze health status in wild animals. Non-invasive measures, analyzed through urine or feces, enable biomarker monitoring without interfering with organisms, important for critically endangered species like orangutans. A measure of urine concentration such as creatinine concentrations or specific gravity is necessary when analyzing urine samples. Here, we measure specific gravity in urine samples from three captive female orangutans using a digital hand-held urine specific gravity refractometer. We compare specific gravity to previously measured creatinine values for two orangutans, and assess the influence of time of collection and refractometer temperature on specific gravity for all three. We found a significant positive correlation between specific gravity and creatinine concentrations (N=1021, Pearson’s R=0.578, p<0.001). While we found no significant correlation between the time that samples were collected and specific gravity readings (N= 314, Pearson’s R = 0.079, p=0.17), readings from samples collected in the morning were slightly but significantly lower (N=255, mean=1.008) than samples collected in the afternoon (N=60, mean=1.009) (independent samples t-test, t312=-1.969, p=0.05). We found a significant negative correlation between specific gravity and the refractometer temperature (Pearson’s R=-0.23, p<0.001). In future studies, specific gravity can be used to determine urine concentration rather than creatinine, which is more costly and requires more time for lab work. Our future research will examine the correlation between specific gravity and creatinine concentrations as orangutans age, and the effects of aging on muscle wasting and reproductive status. 

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5. High-Resolution Magic Angle Spinning (HRMAS) NMR Identifies Oxidative Stress and Impairment of Energy Metabolism by Zearalenone in Embryonic Stages of Zebrafish (Danio rerio), Olive Flounder (Paralichthys olivaceus) and Yellowtail Snapper (Ocyurus chrysurus)

   https://doi.org/10.3390/toxins15060397  

   Annunziato, Mark; Bashirova, Narmin; Eeza, Muhamed_N H; Lawson, Ariel; Benetti, Daniel; Stieglitz, John D; Matysik, Jörg; Alia, A; Berry, John P (June 2023, Toxins)

   Zearalenone (ZEA) is a mycotoxin, commonly found in agricultural products, linked to adverse health impacts in humans and livestock. However, less is known regarding effects on fish as both ecological receptors and economically relevant “receptors” through contamination of aquaculture feeds. In the present study, a metabolomics approach utilizing high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) was applied to intact embryos of zebrafish (Danio rerio), and two marine fish species, olive flounder (Paralichthys olivaceus) and yellowtail snapper (Ocyurus chrysurus), to investigate the biochemical pathways altered by ZEA exposure. Following the assessment of embryotoxicity, metabolic profiling of embryos exposed to sub-lethal concentrations showed significant overlap between the three species and, specifically, identified metabolites linked to hepatocytes, oxidative stress, membrane disruption, mitochondrial dysfunction, and impaired energy metabolism. These findings were further supported by analyses of tissue-specific production of reactive oxygen species (ROS) and lipidomics profiling and enabled an integrated model of ZEA toxicity in the early life stages of marine and freshwater fish species. The metabolic pathways and targets identified may, furthermore, serve as potential biomarkers for monitoring ZEA exposure and effects in fish in relation to ecotoxicology and aquaculture. 

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