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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 -
Frontiers in Molecular Biosciences 2024Nutrition during the perinatal period is an essential component of health and one that can severely impact the correct development of a human being and its overall...
Nutrition during the perinatal period is an essential component of health and one that can severely impact the correct development of a human being and its overall condition, in all the subsequent stages of life. The availability of several compounds, mainly macronutrients and micronutrients, plays a key role in the balanced nutrition of both mother and baby and is a process with direct relation to the gut microbiome. Thus, we hereby refer to the set of small molecules derived from gut microbiome metabolism as the gut metabolome. These continuous processes occurring in the gut of a gestating or lactating mother related to microbial communities and nutrients, can be revealed by metabolomics. In this study, we explore for the first time the gut metabolome of pregnant and lactating women, from our region of Antioquia-Colombia, applying untargeted metabolomics by LC-QTOF-MS, and molecular networking. Regarding the gut metabolome composition of the cohort, we found, key metabolites that can be used as biomarkers of microbiome function, overall metabolic health, dietary intake, pharmacology, and lifestyle. In our cohort, pregnant women evidenced a significantly higher abundance of prostaglandins, alkaloids, corticosteroids, organosilicons, and natural toxins, while in lactating women, lipids stand out. Our results suggest that unveiling the metabolic phenotype of the gut microbiome of an individual, by untargeted metabolomics, allows a broad visualization of the chemical space present in this important niche and enables the recognition of influential indicators of the host's health status and habits, especially of women during this significant perinatal period. This study constitutes the first evidence of the use of untargeted LC-QTOF-MS coupled with molecular networking analysis, of the gut microbiome in a Colombian cohort and establishes a methodology for finding relative abundances of key metabolites, with potential use in nutritional and physiological state assessments, for future personalized health and nutrition practices.
PubMed: 38803424
DOI: 10.3389/fmolb.2024.1250413 -
Animal Nutrition (Zhongguo Xu Mu Shou... Jun 2024This study was conducted to evaluate the effects of M-32 fermented soybean meal (MFSM) on growth, immunity, intestinal morphology, intestinal microbiota, and intestinal...
M-32 fermented soybean meal improves the growth, immunity parameters, intestinal morphology, disease resistance, intestinal microbiota and metabolome in Pacific white shrimp ().
This study was conducted to evaluate the effects of M-32 fermented soybean meal (MFSM) on growth, immunity, intestinal morphology, intestinal microbiota, and intestinal metabolome of Pacific white shrimp (). Four groups of diets were formulated, including control group (30% fish meal and 30% soybean meal [SBM] included in the basal diet) and three experimental groups which MFSM replaced 20% (MFSM20), 40% (MFSM40), and 60% (MFSM60) of SBM in control group, respectively. Results showed that the soluble proteins larger than 49 kDa in MFSM were almost completely degraded. Meanwhile, the crude protein, acid-soluble protein, and amino acid in MFSM were increased. The results of shrimp culture experiment showed that the replacement of SBM with MFSM decreased FCR ( < 0.001) and content of malondialdehyde ( = 0.007) in the experimental groups, and increased weight gain rate ( = 0.006), specific growth rate ( = 0.002), survival rate ( = 0.005), intestinal villus height ( < 0.001), myenteric thickness ( = 0.002), the activities of superoxide dismutase ( = 0.002), and lysozyme ( = 0.006) in experimental groups, as well as increased content of calcium (Ca) and phosphorus () in blood and muscle, and enhanced resistance to infection. The gut microbiota of MFSM groups was significantly different from that of the control group, and the abundance of Actinobacteria and Verrucomicrobia increased significantly in the MFSM60 group, whereas Proteobacteria and Firmicutes decreased. Compared with the control group, there were significant changes in the levels of several intestinal metabolites in the MFSM60 group, including leukotriene C5, prostaglandin A1, taurochenodeoxycholic acid, carnosine, and itaconic acid. The fermentation of SBM by the strain M-32 has the potential to enhance the nutritional quality of SBM, promote the growth of , boost immune response, improve intestinal morphology and microbiota composition, as well as influence intestinal metabolites.
PubMed: 38800738
DOI: 10.1016/j.aninu.2024.03.009 -
The International Journal of... Jul 2024Elevated levels of prostaglandin E have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of...
Elevated levels of prostaglandin E have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of cyclooxygenase enzymatic activity, thereby leading to the suppression of prostaglandin E, are often associated with several side effects due to their non-specific inhibition of cyclooxygenase enzymes. Consequently, the targeted suppression of prostaglandin E production with innovative molecules and/or mechanisms emerges as a compelling therapeutic strategy for the treatment of inflammatory-related diseases. Therefore, in this study, a systematic analysis of 28 pyrazole derivatives was conducted to explore their potential mechanisms for reducing prostaglandin E levels. In this context, the evaluation of these derivatives extended to examining their capacity to reduce prostaglandin Ein vitro in human whole blood, inhibit cyclooxygenase-1 and cyclooxygenase-2 enzymes, modulate cyclooxygenase-2 expression, and suppress oxidative burst in human leukocytes. The results enabled the establishment of significant structure-activity relationships, elucidating key determinants for their activities. In particular, the 4-styryl group on the pyrazole moiety and the presence of chloro substitutions were identified as key determinants. Pyrazole 8 demonstrated the capacity to reduce prostaglandin E levels by downregulating cyclooxygenase-2 expression, and pyrazole-1,2,3-triazole 18 emerged as a dual-acting agent, inhibiting human leukocytes' oxidative burst and cyclooxygenase-2 activity. Furthermore, pyrazole 26 demonstrated effective reduction of prostaglandin E levels through selective cyclooxygenase-1 inhibition. These results underscore the multifaceted anti-inflammatory potential of pyrazoles, providing new insights into the substitutions and structural frameworks that are beneficial for the studied activity.
Topics: Humans; Pyrazoles; Dinoprostone; Respiratory Burst; Leukocytes; Cyclooxygenase 2; Cyclooxygenase 1; Anti-Inflammatory Agents; Structure-Activity Relationship; Cyclooxygenase Inhibitors
PubMed: 38797495
DOI: 10.1016/j.biocel.2024.106599 -
Lipids in Health and Disease May 2024Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction,... (Review)
Review
Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction, leveraging the distinct lipid profiles of cancer patient-derived specimens. This review aims to systematically summarize the application of MS-based lipidomic analysis in prognostic prediction for cancer patients. Our systematic review summarized 38 studies from the past decade that attempted prognostic prediction of cancer patients through lipidomics. Commonly analyzed cancers included colorectal, prostate, and breast cancers. Liquid (serum and urine) and tissue samples were equally used, with liquid chromatography-tandem MS being the most common analytical platform. The most frequently evaluated prognostic outcomes were overall survival, stage, and recurrence. Thirty-eight lipid markers (including phosphatidylcholine, ceramide, triglyceride, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, diacylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidylethanolamine, lysophosphatidic acid, dihydroceramide, prostaglandin, sphingosine-1-phosphate, phosphatidylinosito, fatty acid, glucosylceramide and lactosylceramide) were identified as prognostic factors, demonstrating potential for clinical application. In conclusion, the potential for developing lipidomics in cancer prognostic prediction was demonstrated. However, the field is still nascent, necessitating future studies for validating and establishing lipid markers as reliable prognostic tools in clinical practice.
Topics: Humans; Prognosis; Neoplasms; Lipidomics; Biomarkers, Tumor; Mass Spectrometry; Female; Lipids; Male; Breast Neoplasms; Prostatic Neoplasms; Lysophospholipids; Colorectal Neoplasms
PubMed: 38796445
DOI: 10.1186/s12944-024-02121-0