Fibromyalgia (FM) is characterized by chronic widespread pain. The pathogenesis of FM remains unclear. No specific biomarkers are available. Animal models of FM may provide an opportunity to explore potential biomarkers in a relative homogenous disease condition. Here, we probed the metabolomics profiles of serum and urine in a mouse model of FM induced by intermittent cold stress (ICS). We focused on the role of acid-sensing ion channel 3 (ASIC3) in the metabolomics profiling because ICS treatment induced chronic widespread muscle pain lasting for 1 month in wild-type ( Asic3 +/+ ) but not Asic3 -knockout ( Asic3 −/− ) mice. Serum and urine samples were collected from both genotypes at different ICS stages, including before ICS (basal level) and post-ICS at days 10 (middle phase, P10) and 40 (recovery phase, P40). Control naïve mice and ICS-induced FM mice differed in 1 H-NMR- and LC-MS-based metabolomics profiling. On pathway analysis, the leading regulated pathways in Asic3 +/+ mice were taurine and hypotaurine, cysteine and methionine, glycerophospholipid, and ascorbate and aldarate metabolisms, and the major pathways in Asic3 −/− mice involved amino acid-related metabolism. Finally, we developed an algorithm for the impactful metabolites in the FM model including cis -aconitate, kynurenate, taurine, pyroglutamic acid, pyrrolidonecarboxylic acid, and 4-methoxyphenylacetic acid in urine as well as carnitine, deoxycholic acid, lysoPC(16:0), lysoPC(20:3), oleoyl- L -carnitine, and trimethylamine N -oxide in serum. Asic3 −/− mice were impaired in only muscle allodynia development but not other pain symptoms in the ICS model, so the ASIC3-dependent metabolomics changes could be useful for developing diagnostic biomarkers specific to chronic widespread muscle pain, the core symptom of FM. Further pharmacological validations are needed to validate these metabolomics changes as potential biomarkers for FM diagnosis and/or treatment responses.

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Background: Fibromyalgia (FM) is characterized by chronic widespread pain.Its pathophysiological mechanisms remain poorly understood, and effective diagnosis and treatments are lacking. This study aimed to identify significantly changed biosignatures in FM and propose a novel classification for FM based on pain and soreness (sng) symptoms.Methods: Urine and serum samples from 30 FM patients and 25 controls underwent metabolomic and proteomic profiling.Results: Compared with controls, FM patients showed significant differential expression of three metabolites in urine and five metabolites and eight proteins in serum. Of them, DETP, 4-guanidinobutanoic acid, SM(d18:1/18:0), PC(20:1(11Z)/18:0), S100A7, SERPINB3, galectin-7 and LYVE1 were first reported as potential biomarkers for FM. Furthermore, lactate, 2-methylmaleate and cotinine in urine and lactate, SM(d18:1/25:1), SM(d18:1/26:1) and prostaglandin D2 (PGD2) and PCYOX1, ITIH4, PFN1, LRG1, C8G, C8A, CP, CDH5 and DBH in serum could differentiate pain-(PG) and sng-dominant groups (SG). Lactate, 2-methylmaleate, cotinine, PCYOX1, ITIH4, PFN1 and DBH have a higher level in SG. SM(d18:1/25:1), SM(d18:1/26:1), PGD2, LRG1, C8G, C8A, CP and CDH5 in SG are lower than PG. The omics results indicated disordered free radical scavenging,This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Background The pathophysiology of reversible cerebral vasoconstriction syndrome is unclear. An unbiased systems-based approach might help to illustrate the metabolite profiling and underlying pathophysiology. Methods Urine samples were collected from reversible cerebral vasoconstriction syndrome patients and matched controls recruited in Taipei Veterans General Hospital. 1H-Nuclear magnetic resonance was used to initially explore the metabolic profile, and liquid chromatography tandem mass spectrometry was then used to identify metabolic alterations in reversible cerebral vasoconstriction syndrome. Untargeted metabolite screening was randomly performed on 10 reversible cerebral vasoconstriction syndrome patients and 10 control subjects in the discovery phase. The selected untargeted metabolites were further validated on 47 reversible cerebral vasoconstriction syndrome patients during their ictal stage (with 40 of them having remission samples) and 47 controls in the replication phase. Results and conclusion Six metabolites-hippurate, citrate, 1,3,7-trimethyluric acid, ascorbic acid, D-glucurono-6,3-lactone, and D- threo-isocitric acid-with t-test derived p-value < 0.05 and VIP score >1, were identified as potential urine signatures that can well distinguish reversible cerebral vasoconstriction syndrome subjects at ictal stage from controls. Among them, citrate, hippurate, ascorbic acid, and D-glucurono-6,3-lactone were significantly lower, and 1,3,7-trimethyluric acid and D- threo-isocitric acid were higher in reversible cerebral vasoconstriction syndrome patients. Of these, four selected metabolites, citrate, D-glucurono-6,3-lactone, ascorbic acid, and 1,3,7-trimethyluric acid, returned to normal levels in remission. These metabolites are related to pathways associated with free radical scavenging, with the hub molecules being associated with endothelial dysfunction or sympathetic overactivity. Whether these metabolites and their implicated networks play a role in the pathogenesis of reversible cerebral vasoconstriction syndrome remains to be confirmed.

Aging is a natural human process. It is uniquely individual, taking into account experiences, lifestyle habits and environmental factors. However, many disorders and syndromes, such as osteoporosis, neurodegenerative disorders, cognitive decline etc., often come with aging. The present study was designed to investigate the possible anti-aging effect of N 6 -(4-hydroxybenzyl)adenine riboside (T1-11), an adenosine analog isolated from Gastrodia elata , in a mouse model of aging created by D-galactose (D-gal) and the underlying mechanism, as well as explore the role of adenosine signaling in aging. T1-11 activated A 2A R and suppressed D-gal- and BeSO 4 -induced cellular senescence in vitro . In vivo results in mice revealed that T1-11 abated D-gal-induced reactive oxygen species generation and ameliorated cognitive decline by inducing neurogenesis and lowering D-gal-caused neuron death. T1-11 could be a potent agent for postponing senility and preventing aging-related neuroinflammation and neurodegeneration.