Dataset Information

Untargeted Metabolomics: Biochemical Perturbations in Golestan Cohort Study Opium Users Inform Intervention Strategies.

ABSTRACT: Objective: Over 50 million people worldwide are estimated to use opioids, of which ~30 million use opiates (opium and its derivatives). Use of opiates has been associated with a variety of adverse complications such as neurological and behavioral outcomes, addiction, cancers, diabetes, and cardiovascular disease. While it is well known that opiates exert their neurobiological effects through binding with mu, kappa, and delta receptors to exert analgesic and sedative effects, mechanistic links to other health effects are not well understood. Our study focuses on the identification of biochemical perturbations in Golestan Cohort Study (GCS) opium users. Methods: We used untargeted metabolomics to evaluate the metabolic profiles of 218 opium users and 80 non-users participating in the GCS. Urine samples were obtained from adult (age 40-75) opium users living in the Golestan Province of Iran. Untargeted analysis of urine was conducted using a UPLC-Q-Exactive HFx Mass Spectrometry and a 700 MHz NMR Spectrometry. Results: These GCS opium users had a significantly higher intake of tobacco and alcohol and a significantly decreased BMI compared with non-users. Metabolites derived from opium (codeine, morphine, and related glucuronides), nicotine, and curing or combustion of plant material were increased in opium users compared with non-users. Endogenous compounds which differentiated the opium users and non-users largely included vitamins and co-factors, metabolites involved in neurotransmission, Kreb's cycle, purine metabolism, central carbon metabolism, histone modification, and acetylation. Conclusions: Our study reveals biochemical perturbations in GCS opium users that are important to the development of intervention strategies to mitigate against the development of adverse effects of substance abuse.

SUBMITTER: Li YY

PROVIDER: S-EPMC7783045 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Untargeted Metabolomics: Biochemical Perturbations in Golestan Cohort Study Opium Users Inform Intervention Strategies.

Li Yuan-Yuan YY Ghanbari Reza R Pathmasiri Wimal W McRitchie Susan S Poustchi Hossein H Shayanrad Amaneh A Roshandel Gholamreza G Etemadi Arash A Pollock Jonathan D JD Malekzadeh Reza R Sumner Susan C J SCJ

Frontiers in nutrition 20201222

<b>Objective:</b> Over 50 million people worldwide are estimated to use opioids, of which ~30 million use opiates (opium and its derivatives). Use of opiates has been associated with a variety of adverse complications such as neurological and behavioral outcomes, addiction, cancers, diabetes, and cardiovascular disease. While it is well known that opiates exert their neurobiological effects through binding with mu, kappa, and delta receptors to exert analgesic and sedative effects, mechanistic l ...[more]

PMID: 33415121

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Project description:The health and safety of using e-cigarette products (vaping) have been challenging to assess and further regulate due to their complexity. Inhaled e-cigarette aerosols contain chemicals with under-recognized toxicological profiles, which could influence endogenous processes once inhaled. We urgently need more understanding on the metabolic effects of e-cigarette exposure and how they compare to combustible cigarettes. To date, the metabolic landscape of inhaled e-cigarette aerosols, including chemicals originated from vaping and perturbed endogenous metabolites in vapers, is poorly characterized. To better understand the metabolic landscape and potential health consequences of vaping, we applied liquid chromatography-mass spectrometry (LC-MS) based nontargeted metabolomics to analyze compounds in the urine of vapers, cigarette smokers, and nonusers. Urine from vapers (n = 34), smokers (n = 38), and nonusers (n = 45) was collected for verified LC-HRMS nontargeted chemical analysis. The altered features (839, 396, and 426 when compared smoker and control, vaper and control, and smoker and vaper, respectively) among exposure groups were deciphered for their structural identities, chemical similarities, and biochemical relationships. Chemicals originating from e-cigarettes and altered endogenous metabolites were characterized. There were similar levels of nicotine biomarkers of exposure among vapers and smokers. Vapers had higher urinary levels of diethyl phthalate and flavoring agents (e.g., delta-decalactone). The metabolic profiles featured clusters of acylcarnitines and fatty acid derivatives. More consistent trends of elevated acylcarnitines and acylglycines in vapers were observed, which may suggest higher lipid peroxidation. Our approach in monitoring shifts of the urinary chemical landscape captured distinctive alterations resulting from vaping. Our results suggest similar nicotine metabolites in vapers and cigarette smokers. Acylcarnitines are biomarkers of inflammatory status and fatty acid oxidation, which were dysregulated in vapers. With higher lipid peroxidation, radical-forming flavoring, and higher level of specific nitrosamine, we observed a trend of elevated cancer-related biomarkers in vapers as well. Together, these data present a comprehensive profiling of urinary biochemicals that were dysregulated due to vaping.

Project description:BACKGROUND:Evidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence. METHODS:This study was done in a population-based cohort of 50 045 individuals aged 40-75 years from northeast Iran. Data on participant demographics, diet, lifestyle, opium use, and different exposures were collected upon enrolment using validated questionnaires. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between opium use and different cancer types. FINDINGS:During a median 10 years of follow-up, 1833 participants were diagnosed with cancer. Use of opium was associated with an increased risk of developing all cancers combined (HR 1·40, 95% CI 1·24-1·58), gastrointestinal cancers (1·31, 1·11-1·55), and respiratory cancers (2·28, 1·58-3·30) in a dose-dependent manner (ptrend<0·001). For site-specific cancers, use of opium was associated with an increased risk of developing oesophageal (1·38, 1·06-1·80), gastric (1·36, 1·03-1·79), lung (2·21, 1·44-3·39), bladder (2·86, 1·47-5·55), and laryngeal (2·53, 1·21-5·29) cancers in a dose-dependent manner (ptrend<0·05). Only high-dose opium use was associated with pancreatic cancer (2·66, 1·23-5·74). Ingestion of opium (but not smoking opium) was associated with brain (2·15, 1·00-4·63) and liver (2·46, 1·23-4·95) cancers in a dose-dependent manner (prend<0·01). We observed consistent associations among ever and never tobacco users, men and women, and individuals with lower and higher socioeconomic status. INTERPRETATION:Opium users have a significantly higher risk of developing cancers in different organs of the respiratory, digestive, and urinary systems and the CNS. The results of this analysis show that regular use of opiates might increase the risk of a range of cancer types. FUNDING:World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, US National Cancer Institute, International Agency for Research on Cancer.

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Project description:Neuroprostheses designed to interface with the nervous system to replace injured or missing senses can significantly improve a patient's quality of life. The challenge remains to provide implants that operate optimally over several decades. Changes in the implant-tissue interface may precede performance problems. Tools to identify and characterize such changes using existing clinical measures would be highly valuable. Modern cochlear implant (CI) systems allow easy and regular measurements of electrode impedance (EI). This measure is routinely performed as a hardware integrity test, but it also allows a level of insight into the immune-mediated response to the implant, which is associated with performance outcomes. This study is a 5-year retrospective investigation of MED-EL CI users at the University of Southampton Auditory Implant Service including 176 adult ears (18-91) and 74 pediatric ears (1-17). The trend in EI in adults showed a decrease at apical electrodes. An increase was seen at the basal electrodes which are closest to the surgery site. The trend in the pediatric cohort was increasing EI over time for nearly all electrode positions, although this group showed greater variability and had a smaller sample size. We applied an outlier-labeling rule to statistically identify individuals that exhibit raised impedance. This highlighted 14 adult ears (8%) and 3 pediatric ears (5%) with impedance levels that deviated from the group distribution. The slow development of EI suggests intra-cochlear fibrosis and/or osteogenesis as the underlying mechanism. The usual clinical intervention for extreme impedance readings is to deactivate the relevant electrode. Our findings highlight some interesting clinical contradictions: some cases with raised (but not extreme) impedance had not prompted an electrode deactivation; and many cases of electrode deactivation had been informed by subjective patient reports. This emphasizes the need for improved objective evidence to inform electrode deactivations in borderline cases, for which our outlier-labeling approach is a promising candidate. A data extraction and analysis protocol that allows ongoing and automated statistical analysis of routinely collected data could benefit both the CI and wider neuroprosthetics communities. Our approach provides new tools to inform practice and to improve the function and longevity of neuroprosthetic devices.

Dataset Information

Untargeted Metabolomics: Biochemical Perturbations in Golestan Cohort Study Opium Users Inform Intervention Strategies.

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Untargeted Metabolomics: Biochemical Perturbations in Golestan Cohort Study Opium Users Inform Intervention Strategies.

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