-
Molecular Pain 2024Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked...
Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked prolongation of prostaglandin E (PGE)-induced mechanical hyperalgesia, in vivo. In vitro, priming in nociceptors is characterized by a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. In the present in vitro study we tested the hypothesis that a mu-opioid receptor (MOR) agonist opioid analgesic, morphine, can produce priming by its direct action on nociceptors. We report that treatment of nociceptors with morphine, in vitro, produces a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. Our findings support the suggestion that opioids act directly on nociceptors to induce priming.
Topics: Morphine; Animals; Nociceptors; Dinoprostone; Receptors, Opioid, mu; Analgesics, Opioid; Male; Rats; Ganglia, Spinal; Hyperalgesia; Rats, Sprague-Dawley; Dose-Response Relationship, Drug
PubMed: 38828868
DOI: 10.1177/17448069241260348 -
Journal of Musculoskeletal & Neuronal... Jun 2024To investigate the effects of the combined application of percutaneous vertebroplasty and zoledronic acid on bone mineral density (BMD), bone metabolism, neuropeptide Y...
Effects of Combined Application of Percutaneous Vertebroplasty and Zoledronic Acid on Bone Mineral Density, Bone Metabolism, NPY and PGE2 in Elderly Patients with Osteoporotic Lumbar Vertebral Compression Fracture.
OBJECTIVE
To investigate the effects of the combined application of percutaneous vertebroplasty and zoledronic acid on bone mineral density (BMD), bone metabolism, neuropeptide Y (NPY) and prostaglandin E2 (PGE2) in elderly patients with osteoporotic lumbar vertebral compression fracture (OVCF).
METHODS
The medical records of 118 elderly patients with OVCF who received treatment at our hospital from March 2018 to March 2020 were collected and analyzed retrospectively. Vertebral body height, spinal function, pain degree, and lumbar BMD were compared between the two groups upon admission and three years after the operation. Additionally, the levels of bone-specific alkaline phosphatase (BALP), 25-hydroxyvitamin D (25-(OH)D), beta collagen degradation fragments (β-CTx), neuropeptide Y (NPY), and prostaglandin E2 (PGE2) in the two groups were measured at admission and three years after the operation. Furthermore, complications in the two groups within three years after the operation were documented.
RESULTS
After three years post-operation, the combination group showed a significantly greater improvement in vertebral body height compared to the control group (P<0.05). Moreover, the combination group exhibited a significantly lower Oswestry Disability Index (ODI) score compared to the control group (P<0.05).
CONCLUSION
In elderly patients with OVCF, the combined use of zoledronic acid and percutaneous vertebroplasty is effective in improving lumbar function, BMD, and bone metabolism indices, while reducing pain and the levels of NPY and PGE2.
Topics: Humans; Aged; Female; Fractures, Compression; Zoledronic Acid; Male; Vertebroplasty; Lumbar Vertebrae; Dinoprostone; Bone Density; Spinal Fractures; Neuropeptide Y; Osteoporotic Fractures; Aged, 80 and over; Bone Density Conservation Agents; Retrospective Studies; Combined Modality Therapy
PubMed: 38826002
DOI: No ID Found -
The Journal of Allergy and Clinical... May 2024Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs) and leukotrienes (LTs) with a pathophysiological role in established atopic disease....
INTRODUCTION
Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs) and leukotrienes (LTs) with a pathophysiological role in established atopic disease. However, their role in the inception of disease is unclear. We aimed to investigate the association between urinary eicosanoids in early life and development of atopic disease.
METHODS
We quantified the levels of 21 eicosanoids in urine from children from the COPSAC (age 1 year, n=450) and VDAART (age 3 years, n=575) mother-child cohorts and analyzed the associations with development of wheeze/asthma, atopic dermatitis, and biomarkers of Type-2 inflammation, applying FDR5% multiple testing correction.
RESULTS
In both cohorts, analyses adjusted for environmental determinants showed that higher TXA2 eicosanoids in early life were associated with increased risk of developing atopic dermatitis (P
CONCLUSIONS
This study suggests that early life perturbations in the eicosanoid metabolism are present before the onset of atopic disease in childhood, which provides pathophysiological insight in the inception of atopic diseases.
PubMed: 38825025
DOI: 10.1016/j.jaci.2024.05.022 -
Prostaglandins, Leukotrienes, and... Feb 2024We examined the relationship between Apolipoprotein E (APOE) genotype and n-3 highly unsaturated fatty acid (HUFA) levels in participants of the seAFOod trial, who were... (Randomized Controlled Trial)
Randomized Controlled Trial
APOE genotype, eicosapentaenoic acid (EPA) supplementation and n-3 highly unsaturated fatty acid (HUFA) levels in patients with multiple colorectal polyps: A secondary analysis of the seAFOod polyp prevention trial.
INTRODUCTION
We examined the relationship between Apolipoprotein E (APOE) genotype and n-3 highly unsaturated fatty acid (HUFA) levels in participants of the seAFOod trial, who were undergoing colonoscopy surveillance after removal of colorectal polyps.
METHODS
Baseline and on-treatment (eicosapentaenoic acid [EPA] 2 g daily or placebo for 6 months) levels of n-3 HUFAs, and plasma 18-hydroxyeicosapentaenoic acid (HEPE), were analysed according to APOE genotype (based on polymorphisms rs429358 and rs7412) in 584 participants.
RESULTS
Before treatment, APOE2/2 individuals had lower levels, and APOE4/4 participants had higher levels, of n-3 HUFAs, including EPA, than APOE3/3 counterparts (P < 0.01 for the APOE2/2 versus APOE4/4 comparison). After EPA supplementation, n-3 HUFA levels were not significantly different when stratified by APOE genotype, although APOE4 carriers displayed lower plasma 18-HEPE levels than individuals without an APOE4 allele (P = 0.002).
CONCLUSIONS
APOE genotype is associated with differential n-3 HUFA and 18-HEPE levels in individuals with multiple colorectal polyps.
Topics: Humans; Eicosapentaenoic Acid; Female; Male; Middle Aged; Dietary Supplements; Fatty Acids, Omega-3; Apolipoproteins E; Genotype; Aged; Colonic Polyps; Seafood
PubMed: 38823349
DOI: 10.1016/j.plefa.2024.102623 -
Journal of Animal Science and... Jun 2024The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these...
BACKGROUND
The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce, particularly regarding dietary interventions. Therefore, our study undertook a comprehensive analysis, incorporating both metabolomics and transcriptomics, to explore the effects of a grain-based diet on the functionality of the hypothalamus, as well as on blood and milk in dairy cows.
RESULTS
The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E (PGE) level as a prominent response to the grain-based diet introduction. Furthermore, the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet. Conversely, the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE, including phospholipase A2 (PLA2G4E, PLA2G2A, and PLA2G12B), cyclooxygenase-2 (COX2), and prostaglandin E synthase (PTGES). Additionally, the plasma metabolome analysis indicated a substantial decrease in the level of PGE, along with a decline in adrenal steroid hormones (tetrahydrocortisol and pregnenolone) following the grain-based diet introduction. Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE level. Importantly, PGE was identified as a critical metabolic marker in the hypothalamus, blood, and milk in response to grain intervention. Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus, blood, and milk following the grain-based diet.
CONCLUSIONS
Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet.
PubMed: 38822422
DOI: 10.1186/s40104-024-01034-3 -
World Journal of Gastroenterology May 2024Chronic enteropathy associated with the gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic... (Review)
Review
Chronic enteropathy associated with the gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss. This review explores the potential mechanisms underlying the pathogenesis of CEAS, focusing on the role of -encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2 (PGE2) levels. Studies have suggested that elevated PGE2 levels contribute to mucosal damage, inflammation, and disruption of the intestinal barrier. The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality, as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS. Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel, targeted therapies.
Topics: Humans; Organic Anion Transporters; Intestinal Mucosa; Chronic Disease; Dinoprostone; Intestine, Small; Anti-Inflammatory Agents, Non-Steroidal; Intestinal Diseases; Animals; Gastrointestinal Hemorrhage; Ulcer
PubMed: 38817656
DOI: 10.3748/wjg.v30.i19.2505 -
Scientific Reports May 2024Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully...
Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.
Topics: Animals; Female; Fibroblast Growth Factors; Mice, Transgenic; Mice; Linoleic Acids, Conjugated; Corticosterone; Dinoprostone; Glucagon; Epinephrine; Thermogenesis; Male; Lipid Metabolism; Adipose Tissue, Brown; Fatty Liver; Lipolysis; Hypertriglyceridemia; Adiposity
PubMed: 38816541
DOI: 10.1038/s41598-024-63282-7 -
Science Advances May 2024Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on...
Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit ), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit ), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.
Topics: Humans; Colorectal Neoplasms; Anti-Inflammatory Agents, Non-Steroidal; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Aspirin; Receptors, Prostaglandin E, EP4 Subtype; Male; Genetic Predisposition to Disease; Female; Case-Control Studies; Middle Aged; Genetic Loci; Aged
PubMed: 38809988
DOI: 10.1126/sciadv.adk3121 -
Scientific Reports May 2024The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in...
The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.
Topics: Female; Animals; Phenylacetates; Vagina; Mice; Humans; Chryseobacterium; Candida albicans; Symbiosis; Hydrogen-Ion Concentration; Gardnerella vaginalis; Disease Models, Animal; Vaginitis
PubMed: 38806600
DOI: 10.1038/s41598-024-62947-7 -
Biomedicine & Pharmacotherapy =... Jul 2024Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the... (Review)
Review
Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy.
Topics: Myocardial Reperfusion Injury; Humans; Animals; Hormones; Cardiotonic Agents
PubMed: 38805965
DOI: 10.1016/j.biopha.2024.116764