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Journal of Pain Research 2018Acute application of decanoic acid (DA) in vivo suppresses the excitability of spinal trigeminal nucleus caudalis (SpVc) wide dynamic range (WDR) neurons associated with...
BACKGROUND
Acute application of decanoic acid (DA) in vivo suppresses the excitability of spinal trigeminal nucleus caudalis (SpVc) wide dynamic range (WDR) neurons associated with the short-term mechanical hypoalgesia via muscarinic M receptor signaling; however, the effect of DA on nociceptive trigeminal ganglion (TG) and SpVc nociceptive-specific (NS) neuronal excitability under in vivo conditions remains to be determined. The present study investigated whether this effect could be observed in naive rats.
RESULTS
Extracellular single-unit recordings were made from TG and SpVc NS neurons of pentobarbital-anesthetized rats in response to orofacial noxious mechanical stimuli. DA inhibited the mean firing frequency of both TG and SpVc NS neurons, reaching a maximum inhibition of discharge frequency within 1-5 minutes and reversing after approximately 10-minutes; however, this DA-induced suppression of SpVc NS neuronal firing frequency did not occur in rats administered with methoctramine intravenously prior to stimulation.
CONCLUSION
This in vivo study indicated that firing of TG and SpVc NS neurons induced by mechanical hypoalgesia through peripheral M receptors could be inhibited by acutely administered DA, implicating the potential of DA in the future treatment of trigeminal pain.
PERSPECTIVE
This article presents that the acute DA application suppresses the excitability of TG and SpVc NS neurons associated with mechanical hypoalgesia via peripheral M receptor signaling, supporting DA as a potential therapeutic agent in complementary and alternative medicine for the attenuation of nociception.
PubMed: 30532581
DOI: 10.2147/JPR.S181032 -
Journal of Neurochemistry May 2014The Ketogenic diet (KD) is an effective treatment with regards to treating pharmaco-resistant epilepsy. However, there are difficulties around compliance and...
The Ketogenic diet (KD) is an effective treatment with regards to treating pharmaco-resistant epilepsy. However, there are difficulties around compliance and tolerability. Consequently, there is a need for refined/simpler formulations that could replicate the efficacy of the KD. One of the proposed hypotheses is that the KD increases cellular mitochondrial content which results in elevation of the seizure threshold. Here, we have focussed on the medium-chain triglyceride form of the diet and the observation that plasma octanoic acid (C8) and decanoic acid (C10) levels are elevated in patients on the medium-chain triglyceride KD. Using a neuronal cell line (SH-SY5Y), we demonstrated that 250-μM C10, but not C8, caused, over a 6-day period, a marked increase in the mitochondrial enzyme, citrate synthase along with complex I activity and catalase activity. Increased mitochondrial number was also indicated by electron microscopy. C10 is a reported peroxisome proliferator activator receptor γ agonist, and the use of a peroxisome proliferator activator receptor γ antagonist was shown to prevent the C10-mediated increase in mitochondrial content and catalase. C10 may mimic the mitochondrial proliferation associated with the KD and raises the possibility that formulations based on this fatty acid could replace a more complex diet. We propose that decanoic acid (C10) results in increased mitochondrial number. Our data suggest that this may occur via the activation of the PPARγ receptor and its target genes involved in mitochondrial biogenesis. This finding could be of significant benefit to epilepsy patients who are currently on a strict ketogenic diet. Evidence that C10 on its own can modulate mitochondrial number raises the possibility that a simplified and less stringent C10-based diet could be developed.
Topics: Cell Line; Citrate (si)-Synthase; Decanoic Acids; Diet, Ketogenic; Electron Transport Complex I; Enzyme Activation; Humans; Mitochondria; Neurons
PubMed: 24383952
DOI: 10.1111/jnc.12646 -
Environmental Health : a Global Access... Sep 2022Perfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated...
BACKGROUND
Perfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population.
METHODS
Participants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer.
RESULTS
Perfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (OR = 1.47, 95% CI: 1.19, 1.80; OR = 1.36, 95% CI: 1.09, 1.69; OR = 1.62, 95% CI: 1.19, 2.21).
CONCLUSIONS
Overall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.
Topics: Bayes Theorem; Breast Neoplasms; Case-Control Studies; China; Female; Fluorocarbons; Humans; Prospective Studies; Risk Factors
PubMed: 36085159
DOI: 10.1186/s12940-022-00895-3 -
Molecular Brain Sep 2021The medium-chain fatty acids octanoic acid (C8) and decanoic acid (C10) are gaining attention as beneficial brain fuels in several neurological disorders. The protective...
The medium-chain fatty acids octanoic acid (C8) and decanoic acid (C10) are gaining attention as beneficial brain fuels in several neurological disorders. The protective effects of C8 and C10 have been proposed to be driven by hepatic production of ketone bodies. However, plasma ketone levels correlates poorly with the cerebral effects of C8 and C10, suggesting that additional mechanism are in place. Here we investigated cellular C8 and C10 metabolism in the brain and explored how the protective effects of C8 and C10 may be linked to cellular metabolism. Using dynamic isotope labeling, with [U-C]C8 and [U-C]C10 as metabolic substrates, we show that both C8 and C10 are oxidatively metabolized in mouse brain slices. The C enrichment from metabolism of [U-C]C8 and [U-C]C10 was particularly prominent in glutamine, suggesting that C8 and C10 metabolism primarily occurs in astrocytes. This finding was corroborated in cultured astrocytes in which C8 increased the respiration linked to ATP production, whereas C10 elevated the mitochondrial proton leak. When C8 and C10 were provided together as metabolic substrates in brain slices, metabolism of C10 was predominant over that of C8. Furthermore, metabolism of both [U-C]C8 and [U-C]C10 was unaffected by etomoxir indicating that it is independent of carnitine palmitoyltransferase I (CPT-1). Finally, we show that inhibition of glutamine synthesis selectively reduced C accumulation in GABA from [U-C]C8 and [U-C]C10 metabolism in brain slices, demonstrating that the glutamine generated from astrocyte C8 and C10 metabolism is utilized for neuronal GABA synthesis. Collectively, the results show that cerebral C8 and C10 metabolism is linked to the metabolic coupling of neurons and astrocytes, which may serve as a protective metabolic mechanism of C8 and C10 supplementation in neurological disorders.
Topics: Animals; Animals, Outbred Strains; Astrocytes; Caprylates; Carnitine O-Palmitoyltransferase; Cells, Cultured; Cerebral Cortex; Decanoic Acids; Epoxy Compounds; Glucose; Glutamine; Male; Mice; Mitochondria; Neurons; Oxygen Consumption; Specific Pathogen-Free Organisms; gamma-Aminobutyric Acid
PubMed: 34479615
DOI: 10.1186/s13041-021-00842-2 -
Nutrients Aug 2020The ketogenic diet (KD), a high-lipid and low-carbohydrate diet, has been used in the treatment of epilepsy, neurodegenerative disorders, inborn errors of metabolism and...
The ketogenic diet (KD), a high-lipid and low-carbohydrate diet, has been used in the treatment of epilepsy, neurodegenerative disorders, inborn errors of metabolism and cancer; however, the exact mechanism/s of its therapeutic effect is not completely known. We hypothesized that sirtuins (SIRT)-a group of seven NAD-dependent enzymes and important regulators of energy metabolism may be altered under KD treatment. HT22 hippocampal murine neurons were incubated with two important KD metabolites-beta-hydroxybutyrate (BHB) (the predominant ketone body) and decanoic acid (C10), both accumulating under KD. Enzyme activity, protein, and gene expressions of SIRT 1-4, enzyme capacities of the mitochondrial respiratory chain complexes (MRC), citrate synthase (CS) and gene expression of monocarboxylate transporters were measured in control (untreated) and KD-treated cells. Incubation with both-BHB and C10 resulted in significant elevation of SIRT1 enzyme activity and an overall upregulation of the MRC. C10 incubation showed prominent increases in maximal activities of complexes I + III and complex IV of the MRC and ratios of their activities to that of CS, pointing towards a more efficient functioning of the mitochondria in C10-treated cells.
Topics: 3-Hydroxybutyric Acid; Animals; Citrate (si)-Synthase; Decanoic Acids; Diet, Ketogenic; Energy Metabolism; Gene Expression; Hippocampus; Mice; Mitochondria; Multienzyme Complexes; Neurons; Sirtuins
PubMed: 32784510
DOI: 10.3390/nu12082379 -
Chembiochem : a European Journal of... Feb 2022Cycles of dehydration and rehydration could have enabled formation of peptides and RNA in otherwise unfavorable conditions on the early Earth. Development of the first...
Cycles of dehydration and rehydration could have enabled formation of peptides and RNA in otherwise unfavorable conditions on the early Earth. Development of the first protocells would have hinged upon colocalization of these biopolymers with fatty acid membranes. Using atomic force microscopy, we find that a prebiotic fatty acid (decanoic acid) forms stacks of membranes after dehydration. Using LC-MS-MS (liquid chromatography-tandem mass spectrometry) with isotope internal standards, we measure the rate of formation of serine dipeptides. We find that dipeptides form during dehydration at moderate temperatures (55 °C) at least as fast in the presence of decanoic acid membranes as in the absence of membranes. Our results are consistent with the hypothesis that protocells could have formed within evaporating environments on the early Earth.
Topics: Decanoic Acids; Dehydration; Peptides; Protein Conformation; Temperature
PubMed: 34881485
DOI: 10.1002/cbic.202100614 -
Pathogens (Basel, Switzerland) Jan 2022This study aims to investigate six food additives (octanoic acid, decanoic acid, acesulfame K, aspartame, saccharin, and sucralose) used in foods for the elderly or...
This study aims to investigate six food additives (octanoic acid, decanoic acid, acesulfame K, aspartame, saccharin, and sucralose) used in foods for the elderly or people with dysphagia because of the effect of these food additives on (), which is a keystone pathogen of periodontal diseases. The growth of was inhibited by 5 mM octanoic acid, 1.25 mM decanoic acid, 1.25% acesulfame K, 0.0625% aspartame, 0.03125% saccharin, and 0.625% sucralose. In addition, these food additives showed bactericidal activity for planktonic (5 mM octanoic acid, 5 mM decanoic acid, 0.25% aspartame, 0.25% saccharin, and 5% sucralose). Moreover, biofilm formation was inhibited by 10 mM octanoic acid, 10 mM decanoic acid, 10% acesulfame K, 0.35% aspartame, 0.5% saccharin, and 7.5% sucralose. Moreover, the same concentration of these food additives without aspartame killed in the biofilm. Aspartame and sucralose did not show cytotoxicity to human cell lines at concentrations that affected These findings may be useful in clarifying the effects of food additives on periodontopathogenic bacteria.
PubMed: 35056013
DOI: 10.3390/pathogens11010065 -
BMC Neuroscience Oct 2023Diagnosis and prognostication of severe traumatic brain injury (sTBI) continue to be problematic despite years of research efforts. There are currently no clinically... (Review)
Review
BACKGROUND
Diagnosis and prognostication of severe traumatic brain injury (sTBI) continue to be problematic despite years of research efforts. There are currently no clinically reliable biomarkers, though advances in protein biomarkers are being made. Utilizing Omics technology, particularly metabolomics, may provide new diagnostic biomarkers for sTBI. Several published studies have attempted to determine the specific metabolites and metabolic pathways involved; these studies will be reviewed.
AIMS
This scoping review aims to summarize the current literature concerning metabolomics in sTBI, review the comprehensive data, and identify commonalities, if any, to define metabolites with potential clinical use. In addition, we will examine related metabolic pathways through pathway analysis.
METHODS
Scoping review methodology was used to examine the current literature published in Embase, Scopus, PubMed, and Medline. An initial 1090 publications were identified and vetted with specific inclusion criteria. Of these, 20 publications were selected for further examination and summary. Metabolic data was classified using the Human Metabolome Database (HMDB) and arranged to determine the 'recurrent' metabolites and classes found in sTBI. To help understand potential mechanisms of injury, pathway analysis was performed using these metabolites and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database.
RESULTS
Several metabolites related to sTBI and their effects on biological pathways were identified in this review. Across the literature, proline, citrulline, lactate, alanine, valine, leucine, and serine all decreased in adults post sTBI, whereas both octanoic and decanoic acid increased. Hydroxy acids and organooxygen compounds generally increased following sTBI, while most carboxylic acids decreased. Pathway analysis showed significantly affected glycine and serine metabolism, glycolysis, branched-chain amino acid (BCAA) metabolism, and other amino acid metabolisms. Interestingly, no tricarboxylic acid cycle metabolites were affected.
CONCLUSION
Aside from a select few metabolites, classification of a metabolic profile proved difficult due to significant ambiguity between study design, sample size, type of sample, metabolomic detection techniques, and other confounding variables found in sTBI literature. Given the trends found in some studies, further metabolomics investigation of sTBI may be useful to identify clinically relevant metabolites.
Topics: Adult; Humans; Brain Injuries, Traumatic; Metabolomics; Metabolome; Biomarkers; Serine
PubMed: 37845610
DOI: 10.1186/s12868-023-00824-1 -
Nutrients Jun 2023Pediatric intestinal failure (IF) is the reduction in gut function to below the minimum necessary for the absorption of macronutrients and/or water and electrolytes,...
Pediatric intestinal failure (IF) is the reduction in gut function to below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth. The overall goal in treating IF is to achieve intestinal adaptation; however, the underlying mechanisms have not been fully understood. In this study, by performing single-cell RNA sequencing in pediatric IF patients, we found that decreased Kruppel-Like Factor 4 (KLF4) may serve as the hub gene responsible for the functional deficit in mature enterocytes in IF patients, leading to the downregulation of solute carrier (SLC) family transporters (e.g., SLC7A9) and, consequently, nutrient malabsorption. We also found that inducible KLF4 was highly sensitive to the loss of certain enteral nutrients: in a rodent model of total parenteral nutrition mimicking the deprivation of enteral nutrition, the expression of KLF4 dramatically decreased only at the tip of the villus and not at the bottom of crypts. By using IF patient-derived intestinal organoids and Caco-2 cells as in vitro models, we demonstrated that the supplementation of decanoic acid (DA) could significantly induce the expression of KLF4 along with SLC6A4 and SLC7A9, suggesting that DA may function as a potential therapeutic strategy to promote cell maturation and functional improvement. In summary, this study provides new insights into the mechanism of intestinal adaptation depending on KLF4, and proposed potential strategies for nutritional management using DA.
Topics: Humans; Kruppel-Like Factor 4; Caco-2 Cells; Intestinal Failure; Intestinal Mucosa; Serotonin Plasma Membrane Transport Proteins
PubMed: 37375564
DOI: 10.3390/nu15122660 -
Journal of Integrative Neuroscience Feb 2024Medium-chain triglycerides such as decanoic acid (C10), which is one of the fatty acids that constitute dietary fats, are of substantial interest for their potential...
BACKGROUND
Medium-chain triglycerides such as decanoic acid (C10), which is one of the fatty acids that constitute dietary fats, are of substantial interest for their potential therapeutic effects on neuropsychiatric disorders. However, the effects of C10 on attention-deficit/hyperactivity disorder (ADHD) remain to be studied. We explored the effects of C10 on behavioural activity and antioxidant defences in an experimental animal model of ADHD.
METHODS
To establish an experimental animal model of ADHD, neonatal rats were subjected to unilateral striatal lesions using 6-hydroxydopamine (6-OHDA). The rats sequentially underwent open-field and Y-maze tests before treatment [postnatal day 25 (PN25)]. After the subcutaneous administration of either vehicle or C10 solution (250 mg/kg) for 14 days, the behavioural tests were repeated on PN39. Next, we examined the effects of C10 on the expression of the constitutive antioxidant enzymes catalase and glutathione peroxidase-1/2 and the phase II transcription factor nuclear factor erythroid 2-related factor 2 in four different regions of the rat brain.
RESULTS
Injection of 6-OHDA unilaterally into the striatum resulted in elevated locomotor activity on PN39. The administration of C10 for a period of 14 days did not alter the locomotor hyperactivity. Moreover, the administration of C10 had no significant effects on the expression of proteins related to antioxidant defences in the hippocampus, prefrontal cortex, striatum or cerebellum of both control and lesioned rats.
CONCLUSIONS
The lack of significant effects of C10 in our study may depend on the dose and duration of C10 administration. Further exhaustive studies are needed to verify the efficacy and effects of different doses and treatment durations of C10 and to explore the underlying mechanisms.
Topics: Rats; Animals; Attention Deficit Disorder with Hyperactivity; Oxidopamine; Antioxidants; Disease Models, Animal; Locomotion; Decanoic Acids
PubMed: 38419446
DOI: 10.31083/j.jin2302039