Bioinformatics-driven untargeted metabolomic profiling for clinical screening of methamphetamine abuse.

PURPOSE: Amphetamine-type stimulants are very common, and their usage is becoming a very big social problem all over the world. Thousands of addicts encounter several health problems including mental, metabolic, behavioral and neurological disorders. In addition to these, there are several reports about the elevated risk of tendency on committing criminal cases by addicted persons. Hence, methamphetamine addiction is not only an individual health problem but also a social problem. In our study, we aimed to investigate the pathogenesis of chronic usage of methamphetamine via untargeted metabolomics approach. METHODS: 38 plasma samples were carefully collected and extracted for untargeted metabolomics assay. A liquid-liquid extraction was performed to get as much metabolite as possible from the samples. After the extraction procedure, samples were transferred into vials and they were evaluated via time of flight mass spectrometry instrument. RESULTS: Significantly, altered metabolites were identified by the fold analysis and Welch's test between the groups. 42 different compounds were annotated regarding to data-dependent acquisition method. Pathway analysis were also performed to understand the hazardous effect of methamphetamine on human body. CONCLUSION: It has been reported that drug exposure may affect several metabolic pathways for amino acids, fats, energy metabolism and vitamins. An alternative bioinformatic model was also developed and validated in order to predict the chronic methamphetamine drug users in any criminal cases. This generated model passes the ROC curve analysis and permutation test and classify the controls and drug users correctly by evaluating the metabolic alterations between the groups.

Co-exposure effect of different colour of LED lights and increasing temperature on zebrafish larvae (Danio rerio): Immunohistochemical, metabolomics, molecular and behaviour approaches.

Although there are studies in the literature on the effects of different coloured light-emitting diodes (LEDs) on different organisms, there is limited information on how these effects change with temperature increase. In this study, the effects of blue, green, red and white LED lights on the early development process of zebrafish (Danio rerio (Hamilton, 1822)) were comprehensively investigated. In addition, to simulate global warming, it was examined how a one-degree temperature increase affects this process. For this purpose, zebrafish embryos, which were placed at 4 hpf (hours post fertilization) in an incubator whose interior was divided into four areas, were kept at three different temperatures (28, 29 and 30 °C) for 120 h. The group kept in a dark environment was chosen as the control. The temperature of the control group was also increased at the same rate as the other groups. The results showed that at the end of the exposure period, temperature and light colour caused an increase in body malformations. Histopathological damage and immunopositive signals of HSP 70 and 8-OHdG biomarkers in larval brains, increase in free oxygen radicals, apoptotic cells and lipid accumulation throughout the body, increase in locomotor activity, decrease in heart rate and blood flow, and significant changes in more than thirty metabolite levels were detected. In addition, it has been determined that many metabolic pathways are affected, especially glutathione, vitamin B6 and pyrimidine metabolism. Moreover, it has been observed that a one-degree temperature increase worsens this negative effect. It was concluded that blue light was the closest light to the control group and was less harmful than other light colours. The study revealed that blue light produced results that were most similar to those seen in the control group.

Understanding the side effects of chronic silodosin administration via untargeted metabolomics approach.

BACKGROUND: Precision medicine, which looks for high efficacy and low toxicity in therapies, has increased in popularity with omics technology. This work aims to discover novel and low-toxicity therapy options by examining the complex relationship between silodosin-induced side effects and the metabolomic profiles associated with its administration. MATERIALS AND METHODS: The plasma samples of the control group and silodosin-treated rats were analyzed by LC-Q-TOF-MS/MS. Employing XCMS and MetaboAnalyst software, MS/MS data processed to detect compounds and investigate metabolic pathways. MATLAB 2019b was used for data categorization and multivariate analysis. A thorough comparison of METLIN and HMDB databases revealed 41m/z values with significant differences between the drug-treated and control groups (p <0.01 and fold analysis≥1.5). RESULTS: According to multivariate data analysis, 17-ß-estradiol, taurocholic acid, L-kynurenine, N-formylkynurenine, D-glutamine, L-arginine, prostaglandin H2, prostaglandine G2, 15-keto-prostaglandin E2, calcidiol, thromboxane A2, 5'-methylthioadenosine, L-methionine and S-adenosylmethionine levels changed significantly compared to the control group. Differences in the metabolisms of glycerophospholipid, tyrosine, phenylalanine, arachidonic acid, cysteine and methionine, and biosynthesis of phenylalanine, tyrosine, and tryptophan, and aminoacyl-tRNA have been successfully demonstrated by metabolic pathway analysis. According to this study, vitamin D, D-glutamine, and L-arginine supplements can be recommended to prevent side effects such as fatigue, intraoperative floppy iris syndrome, blurred vision, and dizziness in the treatment of silodosin. Silodosin treatment negatively affected the immune system by affecting the kynurenine and tryptophan metabolism pathways. CONCLUSIONS: The study is a guide for silodosin treatments that offer low side effects and high therapeutic effect within the scope of precision medicine.

LUNGBANK: a novel biorepository strategy tailored for comprehensive multiomics analysis and P-medicine applications in lung cancer.

Background/aim: LUNGBANK was established as part of Project LUNGMARK, pioneering a biorepository dedicated exclusively to lung cancer research. It employs cutting-edge technologies to streamline the handling of biospecimens, ensuring the acquisition of high-quality samples. This infrastructure is fortified with robust data management capabilities, enabling seamless integration of diverse datasets. LUNGBANK functions not merely as a repository but as a sophisticated platform crucial for advancing lung cancer research, poised to facilitate significant discoveries. Materials and methods: LUNGBANK was meticulously designed to optimize every stage of biospecimen handling, from collection and storage to processing. Rigorous standard operating procedures and stringent quality control measures guarantee the integrity of collected biospecimens. Advanced data management protocols facilitate the efficient integration and analysis of various datasets, enhancing the depth and breadth of research possibilities in lung cancer. Results: LUNGBANK has amassed a comprehensive collection of biospecimens essential for unraveling the intricate molecular mechanisms of lung cancer. The integration of state-of-the-art technologies ensures the acquisition of top-tier data, fostering breakthroughs in translational and histological research. Moreover, the establishment of patient-derived systems by LUNGBANK underscores its pivotal role in personalized medicine approaches. Conclusion: The establishment of LUNGBANK marks a significant milestone in addressing the critical challenges of lung cancer research. By providing researchers with high-quality biospecimens and advanced research tools, LUNGBANK not only supports Project LUNGMARK's objectives but also contributes extensively to the broader landscape of personalized medicine. It promises to enhance our understanding of lung cancer initiation, progression, and therapeutic interventions tailored to individual patient needs, thereby advancing the field towards more effective diagnostic and therapeutic strategies.

Investigating the pathogenesis of vitreous in postmortem COVID patients via untargeted metabolomics based bioinformatics model.

SARS-CoV-2 virus has become a worldwide pandemic causing millions of death. This severe disaster lead to a immense panic and stress all over the world. Several studies were dedicated to understand its mechanism, pathogenesis and spreading characteristics. By this way, scientists try to develop different therapy and diagnose strategies. For these reasons, several metabolomics, proteomics and genomics studies were also carried out to improve knowledge in this newly identified virus. In this study, we are aimed to explain the pathogenesis of SARS-CoV-2 exposure on postmortem COVID (+) patients via untargeted metabolomics analysis. To carry out this study, a Data Independent Acquisition SWATH method is optimized and performed. Vitreous samples were analyzed in both MS1 and MS2 ESI(+) mode. An orthogonal Partial Least Square Discriminant Analysis were performed for classification. It was observed that lipid metabolism, several amino acids and oxidative stress biomarkers were strongly affected due to high inflammation and possible cytokine storm.

Analyzing the impact of synthetic and natural steroids: a study of cytochrome P450 metabolism, morphological alterations through metabolomics, and histopathological Examination.

This study focuses on the comparative metabolic profiling and effects of two steroid types: natural and synthetic, specifically 17α-methyl testosterone (17α-MT) at varying concentrations (1.5, 2, and 3 mg/kg) in rainbow trout (Oncorhynchus mykiss). Over a 75-day feeding trial, growth metrics, such as feed efficiency, daily specific growth, live weight gain, total weight gain, and survival rate were systematically monitored every 15 days. At the end of the feeding trial, histopathology, immunohistochemistry, and metabolome analyses were performed in the high-concentration groups (3 mg/kg natural and 3 mg/kg synthetic), in which the lowest survival rate was determined. Key findings reveal that the type of hormone significantly influences growth parameters. While some natural steroids enhanced certain growth aspects, synthetic variants often yielded better results. The metabolomic analysis highlighted significant shifts in the metabolism of tryptophan, purine, folate, primary bile acids, phosphonates, phosphinates, and xenobiotics via cytochrome P450 pathways. Histopathologically, the natural hormone groups showed similar testicular, hepatic, muscular, gill, cerebral, renal, and intestinal tissue structures to the control, with minor DNA damage and apoptosis observed through immunohistochemistry. Conversely, the synthetic hormone groups exhibited moderate DNA damage and mild degenerative and necrotic changes in histopathology.

Dysregulated Leukotriene Metabolism in Patients with COVID-19.

This study aimed to examine the leukotriene metabolism during COVID-19. In total, 180 participants were included in this study, of which 60 were healthy controls, 60 required intensive care units (ICU), and 60 did not require intensive care (non-ICU). The serum levels of 5-lipoxygenase (5-LO), 5-LO activating protein (ALOX5AP), and cysteinyl leukotriene (CYSLT) were measured, and the mRNA expression levels of 5-LO, ALOX5AP, and cysteinyl leukotriene receptor 1 (CYSLTR1) were investigated. Compared with the control group, both the non-ICU and ICU groups had lower levels of 5-LO and mRNA expression. ICU patients had lower levels of 5-LO and mRNA expression than non-ICU patients. CYSLTR1 mRNA expression was highest in the ICU group, followed by the non-ICU group, and healthy controls had the lowest mRNA expression levels. CYSLT levels were higher in the control group than in the non-ICU and ICU groups. CYSLTR1 expression was higher in patients than in controls; therefore, selective leukotriene receptor blockers can be used as treatment options. CYSLTR1 expression was higher in the ICU group than in the non-ICU group. Furthermore, CYSLTR1 mRNA expression may be a promising biomarker of COVID-19 severity.

Evaluating Alterations in Breast Cancer Patients after Recovery Via A PET/CT-Assisted Metabolomics Approach.

OBJECTIVE: Breast cancer is a mortal disease that causes many deaths, especially in women. Improved therapies could contribute positively to survival rates. Metabolomics is an important tool for monitoring the alterations of several metabolites in clinical cases. This study aimed to develop a metabolomics model to observe (via mass spectroscopy) metabolic alterations in patients who suffered from breast cancer (BC), both before and after their recovery. MATERIALS AND METHODS: Grades 1 and 2 invasive ductal carcinoma patients were evaluated based on their positron emission tomography/computed tomography results. Fourteen patients who had fully recovered from BC were subjected to metabolomics analysis. Plasma samples were extracted and analyzed via quadrupole time-of-flight mass tandem spectroscopy. A chemometrics analysis was performed in order to determine the statistically significant metabolites. All the metabolites were annotated via the mummichog algorithm. RESULTS AND DISCUSSION: According to the data analysis, glucose, ornithine, phenyalanine, some vitamins, and metabolites in the fatty acid metabolism were statistically altered after recovery of each patient. CONCLUSION: Untargeted metabolomics studies can be used to understand the etiopathogenesis of breast cancer, finding new biomarkers and alterations of metabolic pathways. After the tumor burden was removed, homeostasis was restored and the concentration of several metabolites began to normalize. This study elucidated the effects of breast cancer at the molecular level.

Global warming and nanoplastic toxicity; small temperature increases can make gill and liver toxicity more dramatic, which affects fillet quality caused by polystyrene nanoplastics in the adult zebrafish model.

Increasing nanoplastics (NPs) pollution may lead to unknown environmental risks when considered together with climate change, which has the potential to become an increasingly important environmental issue in the coming decades. In this context, the present study aimed to evaluate the stressor modelling of polystyrene nanoplastic (PS-NPs) combined with temperature increase in zebrafish. For this purpose, changes in gill, liver and muscle tissues of zebrafish exposed to PS-NPs (25 ppm) and/or different temperatures (28, 29 and 30 °C) for 96 h under static conditions were evaluated. The results obtained emphasize that exposure to PS-NPs stressors under controlled conditions with temperature increase induces DNA damage through stress-induced responses accompanied by degeneration, necrosis and hyperaemia in zebrafish liver and adhesion of lamellae, desquamation and inflammation in lamellar epithelium in gills. Metabolomic analyses also supported changes indicating protein and lipid oxidation, especially PS-NPs-mediated. These findings will contribute to the literature as key data on the effects of PS-NPs presence on protein/lipid oxidation and fillet quality in muscle tissues.

Antioxidant/protective effects of carob pod (Ceratonia siliqua L.) water extract against deltamethrin-induced oxidative stress/toxicity in zebrafish larvae.

In our study, the antioxidant capacity of carob pods water extract (CPWE) against deltamethrin (DM)-induced oxidative stress, a widely used pesticide around the world, was investigated in vitro and in vivo in a zebrafish model. The in vitro antioxidant capacity of the obtained extract was evaluated with different methods using trolox, BHA and BHT standard antioxidants. For in vivo experiments, 4hpf zebrafish embryos were exposed to 10 ppb and 25 ppb DM for 120 h and the larvae were treated with 1-10 and 100 ppm CPWE for 4 h at 72th hours. According to the results obtained, it has been determined that the exposure of zebrafish to DM during the developmental period causes important body malformations, decrease in survival rate, reduction in eye size, shortening in body length and decrease in locomotor activity in the dark period. In addition, according to the results of whole-mount staining, it was determined that DM caused a significant increase in the amount of free oxygen radicals and apoptotic cells. It was also confirmed by metabolome analysis that CPWE application for 4 h reduced DM-induced toxicity and oxidative stress. As a result, it can be said that CPWE has an important antioxidant capacity in eliminating DM-induced oxidative stress.