Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis

Metabolomics, Journal Year: 2020, Volume and Issue: 16(3)

Published: Feb. 27, 2020

Abstract Introduction Osteoarthritis (OA) is the most common form of joint disease, causing pain and disability. Previous studies have demonstrated role lipid mediators in OA pathogenesis. Objectives To explore potential alterations plasma lipidomic profile an established mouse model OA, with a view to identification biomarkers and/or pathology. Methods Pain behaviour was assessed following destabilisation medial meniscus (DMM) (n = 8 mice) compared sham controls 7). Plasma knee joints were collected at 16 weeks post-surgery. samples analysed using ultra-high performance liquid chromatography accurate mass high resolution spectrometry (UHPLC-HR-MS) identify differences lipidome, multivariate univariate statistical analyses. Correlations between behaviour, pathology levels lipids investigated. Results 24 lipids, predominantly from classes cholesterol esters (CE), fatty acids (FA), phosphatidylcholines (PC), N -acylethanolamines (NAE) sphingomyelins (SM), differentially expressed DMM plasma. Six these which increased identified as CE(18:2), CE(20:4), CE(22:6), PC(18:0/18:2), PC(38:7) SM(d34:1). CEs positively correlated all six species cartilage damage. Pathways shown be involved altered homeostasis steroid biosynthesis sphingolipid metabolism. Conclusion We associated OA.

Language: Английский

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Fat of the Gut: Epithelial Phospholipids in Inflammatory Bowel Diseases

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11682 - 11682

Published: Oct. 28, 2021

Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic inflammation within the gastrointestinal (GI) tract. Despite significant progress in understanding etiology and development treatment strategies, IBD remain incurable for thousands patients. Metabolic deregulation is indicative IBD, including substantial shifts lipid metabolism. Recent data showed that changes some phospholipids are very common For instance, phosphatidylcholine (PC)/phosphatidylethanolamine (PE) lysophosphatidylcholine (LPC)/PC ratios associated with severity inflammatory process. Composition also upon towards an increase arachidonic acid decrease linoleic a-linolenic levels. Moreover, certain phospholipid metabolites, such as lysophosphatidylcholine, sphingosine-1-phosphate ceramide, can result enhanced intestinal inflammation, malignancy, apoptosis or necroptosis. Because pathogenesis they may provide basis new strategies to treat IBD. Current attempts aimed at controlling fatty levels through diet via pharmacological manipulation

Language: Английский

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TRPV1: A Common Denominator Mediating Antinociceptive and Antiemetic Effects of Cannabinoids

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 10016 - 10016

Published: Sept. 2, 2022

The most common medicinal claims for cannabis are relief from chronic pain, stimulation of appetite, and as an antiemetic. However, the mechanisms by which reduces pain prevents nausea vomiting not fully understood. Among more than 450 constituents in cannabis, abundant cannabinoids Δ9-tetrahydrocannabinol (THC) cannabidiol (CBD). Cannabinoids either directly or indirectly modulate ion channel function. Transient receptor potential vanilloid 1 (TRPV1) is responsible mediating several modalities it expressed both peripheral central pathways. Activation TRPV1 sensory neurons mediates nociception ascending pathway, while activation descending involves rostral ventral medulla (RVM) periaqueductal gray (PAG), antinociception. channels thought to be implicated neuropathic/spontaneous perception setting impaired antinociceptive control. also can cause release calcitonin gene-related peptide (CGRP) other neuropeptides/neurotransmitters nerve terminals, including vagal terminal innervating gut that forms synapses at nucleus tractus solitarius (NTS). One adverse effects use paradoxical cannabis-induced hyperemesis syndrome (HES), becoming common, perhaps due wider availability cannabis-containing products containing higher levels cannabinoids. Although, mechanism HES unknown, effective treatment options include hot-water hydrotherapy topical application capsaicin, activate may involve vagal-NTS area postrema (AP) pathway. In this review, we will delineate their role antinociceptive/nociceptive antiemetic/emetic involving peripheral, spinal, supraspinal structures.

Language: Английский

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Garcinol Reduces Obesity in High‐Fat‐Diet‐Fed Mice by Modulating Gut Microbiota Composition

Molecular Nutrition & Food Research, Journal Year: 2018, Volume and Issue: 63(2)

Published: Dec. 5, 2018

Scope Obesity has become a major health problem worldwide and is associated with low‐grade chronic inflammation intestinal dysbiosis. This study conducted to investigate the chemopreventive effects of garcinol, polyisoprenylated benzophenone derivative isolated from fruit rind Garcinia indica . How garcinol protects against obesity in high‐fat diet (HFD)‐induced mice delineated whether its anti‐obesity are related gut microbiota been determined. Methods results The show that reduces HFD‐fed body weight gain relative visceral adipose tissue fat dose‐dependent manner. Furthermore, markedly plasma levels glutamate pyruvate transaminase, total cholesterol, triacylglycerol. 16S rRNA gene sequence data indicate not only reverses HFD‐induced dysbiosis—as indicated by decreased Firmicutes‐to‐Bacteroidetes ratios—but also controls increasing commensal bacteria, Akkermansia In addition, AMP‐activated protein kinase α signaling pathway involved adipocyte adipogenesis affected garcinol. Conclusion Taken together, these demonstrate for first time can prevent may be used as novel modulator dysbiosis obesity‐related metabolic disorders.

Language: Английский

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Cannabis for cancer – illusion or the tip of an iceberg: a review of the evidence for the use of Cannabis and synthetic cannabinoids in oncology

Expert Opinion on Investigational Drugs, Journal Year: 2018, Volume and Issue: 28(3), P. 285 - 296

Published: Dec. 21, 2018

A flowering plant of variegated ingredients and psychoactive qualities, Cannabis has long been used for medicinal recreational purposes. Regulatory approvals have gained across a broad range palliative therapeutic indications, in some cases, included standard treatment guidelines.The use cannabinoid-based-medicines oncology is summarized this article. Cannabinoids are classified according to natural synthetic subtypes their mechanisms action expounded. The variability available products discussed the clinical context data regarding chemotherapy-induced nausea vomiting, cancer-related pain, anorexia, insomnia, anxiety presented. Moreover, immunological antineoplastic effects preclinical trials addressed. Concepts such as synergism or opposition with conventional modalities, sequence administration dosage, molecular cross-talk malignancy-cannabinoid congruence, explored. Finally, side-effects, limitations trial design legislation barriers related.Sufficient evidence supports indications oncology; however, patients should be carefully selected, guided followed. Promising research suggests potent activity, but more must accrued before conclusions can drawn.

Language: Английский

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