Metabolites最新文献

Background: Fibroblast activation protein (FAP) is a cell surface glycoprotein expressed by myofibroblasts in areas of active tissue remodeling. It plays a potentially important role in cardiac remodeling, atherosclerotic plaque formation, and plaque rupture. Given the distinct pathophysiology and morphology of different forms of atherosclerosis, we analyzed FAP expression in human coronary vessels with no coronary artery disease, atherosclerotic plaques at different levels of progression, and other distinct forms of coronary disease in post bypass vein grafting and cardiac allograft vasculopathy after a heart transplant. Methods: Immunohistochemical staining with monoclonal F19 mouse anti-human FAP antibody was performed to identify FAP in human atherosclerotic plaques, coronary bypass atherosclerosis, and post-transplant arteriosclerosis. The presence and distribution of FAP in different types and stages of human atherosclerosis were compared. Results: There was no FAP staining in patients with no significant coronary disease. All different types of human atherosclerotic lesioning lesions showed the presence of FAP expression, with different staining patterns in advanced atherosclerotic plaque, vein graft atherosclerosis lesions, and arteriosclerosis after a heart transplant. Conclusions: These data suggest that FAP may be a potential diagnostic marker and target for interventions, not only in coronary atherosclerotic plaque, but also in other forms of coronary disease, which have distinct pathophysiologies and currently limited treatment options.

This Special Issue was published to celebrate 10+ years of research and services at the UC Davis West Coast Metabolomics Center (WCMC) [...].

Objectives: Antibiotic-resistant bacterial infections are a growing global concern. A natural remedy for bacterial infections could be available in the Selenicereus undatus fruit, but its antibacterial and biochemical properties are not fully known.

Methods: In this study, the biochemical composition and antibacterial, antioxidant, and cytotoxic activities of the Jindu No. 1 (JD) and Bird's Nest (YW) dragon fruit varieties and their potential effects against E. coli, Pseudomonas sp., and Staphylococcus sp. were scrutinized.

Results: The JD fruit extract showed higher antibacterial activity than the YW variety against E. coli, Pseudomonas sp., and Staphylococcus sp. in vitro. Additionally, the JD variety demonstrated more significant antioxidant activity than the YW variety and showed less cytotoxic activity. The JD variety had a higher glucose content, while the YW variety had a higher fructose content, and the phytoconstituents analysis confirmed 659 metabolites in total from the two varieties. Through in silico analyses, phytoconstituents were evaluated to identify potential drug molecules against the selected bacterial strain. Moreover, the molecular docking study revealed that riboprobe and Z-Gly-Pro might be effective against E. coli, 4-hydroxy retinoic acid, and that succinyl adenosine may target Pseudomonas sp., and xanthosine and 2'-deoxyinosine-5'-monophosphate may be effective against Staphylococcus sp. These results were further validated by 100 ns Molecular Dynamics (MD) simulation, and all of the selected compounds exhibited acceptable ADMET features.

Conclusions: Therefore, phytoconstituents from S. undatus fruit varieties could be employed to fight human bacterial diseases, and future studies will support the continuation of other biological activities in medical research.

Background/objectives: Menopause and related metabolites are associated with mortality. However, the relationship between earlier menopause, premature mortality, and the role of metabolomic signatures remains underexplored. This study investigated the association between earlier menopause and premature mortality, and the mediating effect of metabolomic signatures.

Methods: This prospective cohort study used data from the UK Biobank, including 33,687 post-menopausal women aged 40-69 years. Age at menopause was obtained from a baseline self-reported questionnaire and analyzed both as a continuous variable and in categories (<40, 40-49, and ≥50 years). Premature mortality was defined as deaths before 75 years. Cox regression was used to estimate hazard ratios (HRs), and elastic net regression identified metabolomic signatures related to menopause age. Mediation analysis was conducted to assess the proportion of the association explained by the metabolomic signature.

Results: During a median follow-up of 13.7 years, 1612 cases of premature mortality occurred. Compared to menopause at ≥50 years, earlier menopause (HR 1.17, 95% CI 1.04-1.30) and premature menopause (HR 1.60, 95% CI 1.28-2.00) were associated with higher risks of premature mortality. A metabolomic signature inversely associated with premature mortality (HR per SD increment, 0.79; 95% CI, 0.75-0.83) mediated 13.6% (95% CI, 1.9%-28.3%) of the association between earlier menopause and premature mortality.

Conclusions: Earlier menopause is associated with an increased risk of premature mortality, partially mediated by a metabolomic signature related to age at menopause. These findings highlight the importance of metabolomic profiling in understanding menopause and mortality risks.

Background; Turmeric starch (TS) has gained significant attention due to its potential health benefits. Rich in resistant starch (RS) and higher in phosphorus, TS is anticipated to possess properties of high-phosphorus-type RS. Objectives; To understand the host physiology of TS, this study investigated the dose-dependent effects of TS on colonic fermentation in rats. Methods; Four experimental diets containing different levels of TS (5%, 10%, and 20% w/w) were formulated and fed to male Fischer 344 rats for two weeks and compared with rats fed a 0% TS diet (TS0). Results; Results showed that increasing the dose of TS resulted in reduced body weight gain, lower visceral tissue weight, and increased cecal mucin and IgA levels compared with the TS0 group. Further, fecal dry weight increased dose-dependently parallel to the starch excretion rate. Higher doses of TS resulted in increased short chain fatty acid (SCFA) production, specifically cecal acetate content, as well as in a dose-dependent decrease in the cecal pH level. However, this study did not observe a positive effect of TS on colonic alkaline phosphatase (ALP) activity, and the impact on small intestinal ALP activity remains unclear. Notably, beneficial bacteria such as the family Oscillospiraceae, genus Lachnospiraceae NK4A136 group, and Ruminococcus spp. were found to have been enriched in the TS-fed groups, further supporting the beneficial effects of TS on gut microbiota and SCFA production. Additionally, the genus Mucispirillum, which is known to possess beneficial and opportunistic pathogenic traits under immunocompromised states, was found in the TS-fed groups. Conclusions; According to these results, it is clear that TS served as a prebiotic substrate in rats, with a notable modulation of the microbial composition.

Background: Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that occurs predominantly in premature infants and is characterized by the inflammation and necrosis of the intestine, showing high morbidity and mortality rates. Despite decades of research efforts, a specific treatment is currently lacking, and preventive strategies are the mainstays of care. This review aims to help understand the complex interplay between gut microbiota and their metabolites in NEC pathogenesis. In particular, we focused on how these factors can influence gut health, immune responses, and intestinal barrier integrity. Discussion: Current research has increasingly focused on the role of the gut microbiota and their metabolites in NEC pathogenesis, thanks to their involvement in modulating gut health, immune responses, and intestinal barrier integrity. Conclusions: A deeper understanding of the interplay between gut microbiota and their metabolites is essential for developing personalized strategies to prevent NEC. By targeting these microbial interactions, new therapeutic approaches may emerge that offer improved outcomes for preterm infants at a high risk of NEC.

Background: Peclinical and clinical studies have revealed that ezetimibe, an approved cholesterol-absorption inhibitor, is rapidly and extensively metabolized to a more potent metabolite, ezetimibe glucuronide. Since different species are commonly used in the pharmacokinetic and pharmacodynamic studies of ezetimibe, it is essential to determine the species difference in glucuronidation of ezetimibe in order to accurately evaluate ezetimibe's pharmacokinetics and pharmacodynamics. The purpose of the study was to compare species differences in ezetimibe glucuronidation rates using intestinal microsomes from humans, rats, mice, monkeys, and dogs.

Method: Intestinal microsomes from different species were used to assess the ezetimibe glucuronidation rates. Multiple substrate concentrations at 0.5, 2, 5, 10, 20, 30, 40, and 50 µM were tested and fitted into the Michaelis-Menten model to determine the enzyme kinetic parameters.

Results: The results showed that the glucuronidation rates with these tested species were significantly different. Kinetic studies revealed that the maximum metabolic rate (V_max) was higher in monkeys (3.87 ± 0.22 nmol/mg/min) than that in rat (2.40 ± 0.148 nmol/mg/min) and mouse (2.23 ± 0.10 nmol/mg/min), and then human (1.90 ± 0.08 nmol/mg/min) and dog (1.19 ± 0.06 nmol/mg/min). The CLint was an 8.17-fold difference among these species, following the order of mouse > dog > human > rat = monkey.

Conclusions: The study revealed that the rate of ezetimibe glucuronidation in the intestine was different in different species and has an impact on ezetimibe glucuronidation in the intestine. When analyzing the pharmacodynamics, pharmacokinetics, or toxicology of ezetimibe using different models, these species differences must be taken into consideration.

Background: Anxiety refers to the pathological persistence and intensification of emotional responses to danger, affecting health from psychological and physical aspects. Serotonin is an important neurotransmitter involved in the onset of anxiety.

Methods and results: To explore the biological changes in the formation of anxiety in crustaceans under the regulation of serotonin, we applied the open field-like test method for assessing anxiety states of larval Portunus trituberculatus, a highly aggressive crustacean species with a more simple neural structure compared with rodents and mammals. Compared with the control group, serotonin treatment resulted in a significant decrease in the time spent by the larvae in the central zone, suggesting anxiety-like behavior. Clonazepam treatment reversed this result and provided further evidence that the behavior of larval P. trituberculatus displayed anxiety. Moreover, a non-targeted metabolomic analysis found a significant alteration in the metabolites involved in tryptophan metabolism pathways associated with anxiety, including L-kynurenine, N-acetyl serotonin, and serotonin. These metabolites are involved in the serotonin pathway, the kynurenine pathway, and other pathways that affect anxiety through tryptophan metabolism. There were no significant differences in tryptophan metabolism levels between the control and clonazepam treatment groups.

Conclusions: Our results demonstrate the possible existence of anxiety-like behavior in the larvae of P. trituberculatus from two perspectives. Being a species with a simpler neural structure than that of mammals, the larvae of P. trituberculatus offer a convenient model for studying the mechanisms of anxiety in crustaceans.

Background and aims: Mastitis is one of the main complications during breastfeeding and contributes to the cessation of breastfeeding. However, the etiopathogenesis and diagnosis of mastitis are complex and not yet well defined. We aimed to identify metabolic and lipidic changes in human milk during acute and subacute mastitis in order to detect potential biomarkers of mastitis. Methods: We conducted a pilot case-control study including 14 breastfeeding women with acute mastitis, 32 with subacute mastitis symptoms, and 19 without any mastitis symptoms (control). Milk samples were collected and analyzed by proton nuclear magnetic resonance (H-NMR) for metabolomics analysis. To assess the association between the significant metabolites and lipids and the development of acute and subacute mastitis, multi-adjusted logistic regression models were developed. Results: The NMR-based metabolomics approach was able to identify and quantify a total of 40 metabolites in breast milk samples. After adjusting for confounding variables, acute mastitis was significantly associated with acetate (OR 3.9 IC 1.4-10.8), total cholesterol (OR 14 CI 3.2-62), esterified cholesterol (OR 3.3 CI 1.9-5.8), and sphingomyelin (OR 2.6 CI 1.2-5.8). The other metabolites presented weak association (OR < 2.5). Subacute mastitis was significantly associated with glutamine, lysophosphatidylcholine, phosphatidylcholine, plasmalogen, and total polyunsaturated fatty acids, but only cholesterol showed a strong association (OR > 2.5) with an OR of 2.6 (IC 1.1-6.6). Conclusions: Metabolic alteration in breast milk occurs during a process of both acute and subacute mastitis. Acetate, esterified cholesterol, lysophostidylcholine, and polyunsaturated fatty acids increased in both acute and subacute mastitis. However, according to the multi-adjusted regression logistic models, the candidate biomarkers for acute and subacute mastitis are cholesterol, lysophosphatidylcoholine, phosphatidylcholine, plasmalogen, and polyunsaturated fatty acids.

Background: There is a close relationship between breast muscle glucose metabolism, peripheral 5-hydroxytryptamine (5-HT), and myopathies in animals. Here, this study aimed to investigate the effects of different photoperiods on peripheral 5-HT metabolism, white striping (WS), and wooden breast (WB) in broilers. Methods: A total of 216 healthy 5-day-old (d) Arbor Acres (AA) male broilers were randomly assigned to 12L:12D, 18L:6D, and 24L:0D photoperiods for 4 weeks. Results: Compared with the 12L:12D photoperiod, we found the WB score in broilers was significantly increased in the 18L:6D and 24L:0D photoperiod at week 4 (p < 0.05). Muscle glycogen was significantly reduced (p < 0.05) and glycolysis was promoted in the breast muscles of broilers under the 18L:6D and 24L:0D photoperiods at week 2 and 4. Peripheral 5-HT concentrations, the mRNA expression of tryptophan hydroxylase 1 (TPH1) and serotonin transporter (SERT) in the cecal mucosa, and 5-hydroxytryptamine receptor 2A (5-HTR_2A) mRNA expression in the breast muscle of broilers significantly up-regulated in the 18L:6D and 24L:0D photoperiod at week 2 and 4 (p < 0.05). Conclusions: Our findings revealed that extending the photoperiod improved the breast muscle growth rate, but up-regulated 5-HT synthesis and secretion to higher peripheral 5-HT, induced breast muscle glucose metabolism disorder, and increased WB incidence rates in broilers.