PubMed
Detection of Subclinical Rejection in Pediatric Kidney Transplantation: Current and Future Practices
Pediatr Transplant. 2024 Sep;28(6):e14836. doi: 10.1111/petr.14836.ABSTRACTINTRODUCTION: The successes in the field of pediatric kidney transplantation over the past 60 years have been extraordinary. Year over year, there have been significant improvements in short-term graft survival. However, improvements in longer-term outcomes have been much less apparent. One important contributor has been the phenomenon of low-level rejection in the absence of clinical manifestations-so-called subclinical rejection (SCR).METHODS: Traditionally, rejection has been diagnosed by changes in clinical parameters, including but not limited to serum creatinine and proteinuria. This review examines the shortcomings of this approach, the effects of SCR on kidney allograft outcome, the benefits and drawbacks of surveillance biopsies to identify SCR, and new urine and blood biomarkers that define the presence or absence of SCR.RESULTS: Serum creatinine is an unreliable index of SCR. Surveillance biopsies are the method most utilized to detect SCR. However, these have significant drawbacks. New biomarkers show promise. These biomarkers include blood gene expression profiles and donor derived-cell free DNA; urine gene expression profiles; urinary cytokines, chemokines, and metabolomics; and other promising blood and urine tests.CONCLUSION: Specific emphasis is placed on studies carried out in pediatric kidney transplant recipients.TRIAL REGISTRATION: ClinicalTrials.gov: NCT03719339.PMID:39147695 | DOI:10.1111/petr.14836
Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse
Cell Biol Toxicol. 2024 Aug 16;40(1):71. doi: 10.1007/s10565-024-09901-5.ABSTRACTThe simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.PMID:39147926 | DOI:10.1007/s10565-024-09901-5
Unraveling the formation mechanism of aroma compounds in pork during air frying using UHPLC-HRMS and Orbitrap Exploris GC-MS
Food Res Int. 2024 Sep;192:114816. doi: 10.1016/j.foodres.2024.114816. Epub 2024 Jul 24.ABSTRACTLipids are the key matrix for the presence of odorants in meat products. The formation mechanism of odorants of air-fried (AF) pork at 230 °C was elucidated from the perspectives of lipids and heat transfer using physicochemical analyses and multidimensional statistics. Twenty-nine key aroma compounds were identified, with pyrazines predominantly contributing to the roasty aroma of air-fried roasted pork. Untargeted lipidomics revealed 1184 lipids in pork during roasting, with phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triglyceride (TG) being the major lipids accounting for about 60 % of the total lipids. TG with C18 acyl groups, such as TG 16:1_18:1_18:2 and TG 18:0_18:0_20:3, were particularly significant in forming the aroma of AF pork. The OPLS-DA model identified seven potential biomarkers that differentiate five roasting times, including PC 16:0_18:3 and 2-ethyl-3,5-dimethylpyrazine. Notably, a lower specific heat capacity and water activity accelerated heat transfer, promoting the formation and retention of odorants in AF pork.PMID:39147509 | DOI:10.1016/j.foodres.2024.114816
Non-target and target quantitative metabolomics with quantitative aroma evaluation reveal the influence mechanism of withering light quality on tea aroma and volatile metabolites evolution
Food Res Int. 2024 Sep;192:114773. doi: 10.1016/j.foodres.2024.114773. Epub 2024 Jul 15.ABSTRACTWithering is the first and key process that influences tea quality, with light quality being a key regulatory factor. However, effects of withering light quality (WLQ) on transformation and formation pathways of tea aroma and volatile metabolites (VMs) remain unclear. In the present study, four WLQs were set up to investigate their effects on tea aroma and VMs. The results showed that blue and red light reduced the grassy aroma and improved the floral and fruity aroma of tea. Based on GC-MS/MS, 83 VMs were detected. Through VIP, significant differences, and OAV analysis, 13 key differential VMs were screened to characterize the differential impacts of WLQ on tea aroma. Further analysis of the evolution and metabolic pathways revealed that glycoside metabolism was the key pathway regulating tea aroma through WLQ. Blue light withering significantly enhanced glycosides hydrolysis and amino acids deamination, which was beneficial for the enrichment of floral and fruity VMs, such as geraniol, citral, methyl salicylate, 2-methyl-butanal, and benzeneacetaldehyde, as well as the transformation of grassy VMs, such as octanal, naphthalene, and cis-3-hexenyl isovalerate, resulting in the formation of tea floral and fruity aroma. The results provide theoretical basis and technical support for the targeted processing of high-quality tea.PMID:39147497 | DOI:10.1016/j.foodres.2024.114773
Characterization of gelatin-oxidized riclin cryogels and their applications as reusable ice cubes in shrimp preservation
Food Res Int. 2024 Sep;192:114766. doi: 10.1016/j.foodres.2024.114766. Epub 2024 Jul 14.ABSTRACTTraditional ice is usually employed to preserve food freshness and extend shelf life. However, ice cannot bear repeated freeze - thaw cycles during the transportation and retailing process, resulting in microbial cross-contamination and spoilage of foods. Herein, succinoglycan riclin was oxidated (RO) and crosslinked with gelatin (Ge), the Ge-RO cryogels were prepared via Schiff base reaction and three freeze - thaw cycles. The Ge-RO cryogels showed improved storage modulus (G') and thermal stability compared with pure gelatin hydrogel. The polymer framework of Ge-RO gels exhibited stable properties against ice crystals destructions during nine freeze - thaw treatments. During the storage and repeated freeze - thaw treatments of shrimps, Ge-RO cryogels exhibited a remarkable preservation effect on shrimps, and their freshness was evaluated using an electronic nose technique equipped with ten sensors. The results demonstrated that the shrimp muscle preserved in ice generated off-odors and resulted in high sensor responses. The sensor responses were reduced sharply of shrimps preserved in cryogels. Moreover, 1H NMR-based metabolomics analysis revealed that shrimps in Ge-RO cryogels group reversed the metabolic perturbations compared with the traditional ice group, the metabolic pathways were related to energy metabolism, nucleotide metabolism, and amino acid metabolism, which provide new clues to the freshness of shrimps. Furthermore, RO exhibited superior antimicrobial activity against E. coli and S. aureus microorganisms. Thus, the crosslinked cryogels are potentially applicable to food preservation, offering sustainable and reusable solutions against traditional ice.PMID:39147487 | DOI:10.1016/j.foodres.2024.114766
Comprehensive metabolomics and chemometrics unravel potential anti-diabetic metabolites of pumpkin (Cucurbita pepo L.) fruits through UPLC-QqQ-MS and GC-MS analyses
Food Res Int. 2024 Sep;192:114771. doi: 10.1016/j.foodres.2024.114771. Epub 2024 Jul 15.ABSTRACTThis comprehensive study explores the phytoconstituents of different parts of pumpkin (Cucurbita pepo) including flesh, peel, seeds, pumpkin juice, and pumpkin seed oil. Utilizing advanced analytical techniques including UPLC-QqQ-MS and GC-TSQ-MS combined with multivariate statistical analysis, 94 distinct chromatographic peaks from various chemical classes were annotated. Predominant classes included phenolic acids, flavonoids, cucurbitacins, amino acids, triterpenoids, fatty acids, sterols, carotenoids, and other compounds. For more comprehensive chemical profiling of the tested samples, fractionation of the different parts of the fruit was attempted through successive solvent extraction. The unsaponifiable part of the oils, analyzed by GC, showed that the phytosterols, namely ß-sitosterol, and stigmasterol are in the majority. All pumpkin extracts showed significant inhibition of carbohydrase enzymes and glucose uptake promotion by cells. Pumpkin flesh butanol fraction exhibited potent α-glucosidase inhibition, while pumpkin defatted seed methylene chloride fraction showed strong α-amylase inhibition. Additionally, pumpkin seed oil and defatted seed petroleum ether fraction demonstrated high glucose uptake activity. Bioactive metabolites including vaccenic acid, sinapic acid, kuguacin G, luteolin hexoside, delta-7-avenasterol, cucurbitosides and others were unveiled through OPLS multivariate models elucidating the anti-diabetic potential of pumpkin. These findings support the use of pumpkin as a functional food, offering insights into its mechanisms of action in diabetes management.PMID:39147478 | DOI:10.1016/j.foodres.2024.114771
Integrative metabolomics and chemometrics depict the metabolic alterations of differently processed red kidney beans (Phaseolus vulgaris L.) and in relation to in-vitro anti-diabetic efficacy
Food Res Int. 2024 Sep;192:114786. doi: 10.1016/j.foodres.2024.114786. Epub 2024 Jul 17.ABSTRACTRed kidney beans (RKB) serve as a powerhouse packed with a plethora of largely unexplored extraordinary chemical entities with potential significance. However, their nutraceutical applications as a functional hypoglycemic food still lag behind and warrant further investigation. With a scope to optimize chemical and biological traits of RKB, green modification approaches (processing methods) seem inevitable. Accordingly, the current study offered the first integrative workflow to scrutinize dynamic changes in chemical profiles of differently processed RKB and their potential entanglements on diabetes mitigation using Ultra Performance Liquid Chromatography-mass spectrometry (UPLC-MS/MS) coupled with chemometrics. Different physical and biological processing treatments namely germination, fermentation, cooking and dehulling were preliminarily implemented on RKB. Complementarily, the concomitant metabolite alterations among differently processed RKB were monitored and interpreted. Next, an in-vitro α-amylase and α-glycosidase inhibitory testing of the differently processed samples was conducted and integrated with orthogonal projection to latent structures (OPLS) analysis to pinpoint the possible efficacy compounds. A total of 72 compounds spanning fatty acids and their glycerides, flavonoids, phenolic acids, amino acids, dipeptides, phytosterols and betaxanthins were profiled. Given this analysis and compared with raw unprocessed samples, it was found that flavonoids experienced notable accumulation during germination while both fermentation and dehulling approaches sharply intensified the content of amino acids and dipeptides. Comparably, Fatty acids, phytosterols and betaxanthins were unevenly distributed among the comparable samples. Admittedly, OPLS-DA revealed an evident discrimination among the processed samples assuring their quite compositional discrepancies. In a more targeted approach, kaempferol-O-sophoroside, quercetin, carlinoside and betavulgarin emerged as focal discriminators of sprouted samples while citrulline, linoleic acid, linolenoyl-glycerol and stigmasterol were the determining metabolites in cooked samples. Our efficacy experimental findings emphasized that the different RKB samples exerted profound inhibitory actions against both α-amylase and α-glycosidase enzymes with the most promising observations in the case of sprouted and cooked samples. Coincidently, OPLS analysis revealed selective enhancement of possible efficacy constituents primarily citrulline, formononetin, gamabufotalin, kaempferol-O-sophoroside, carlinoside, oleic acid and ergosterol in sprouted and cooked samples rationalizing their noteworthy α-amylase and α-glucosidase inhibitory activities. Taken together, this integrated work provides insightful perspectives beyond the positive impact of different processing protocols on bioactives accumulation and pharmacological traits of RKB expanding their utilization as functional hypoglycemic food to rectify diabetes.PMID:39147477 | DOI:10.1016/j.foodres.2024.114786
Exploring the potential of red pitaya pulp (Hylocererus sp.) as a plant-based matrix for probiotic delivery and effects on betacyanin content and flavoromics
Food Res Int. 2024 Sep;192:114820. doi: 10.1016/j.foodres.2024.114820. Epub 2024 Jul 23.ABSTRACTThis study evaluated the potential of red pitaya pulp fermented with Lacticaseibacillus paracasei subsp. paracasei F-19 (F-19) as a base for probiotic products. Physicochemical parameters, sugar, betacyanin, and phenolic contents, and antioxidant activity were analyzed over 28 days at 4 °C and compared to a non-fermented pulp, and to a pulp fermented with Bifidobacterium animalis subsp. lactis BB-12 (BB-12). Volatile compounds were identified using HS-SPME/GC-MS. Probiotic viability during storage and survival through in vitro-simulated gastrointestinal tract (GIT) stress were assessed. Red pitaya pulp, rich in moisture (85.83 g/100 g), carbohydrates (11.65 g/100 g), and fibers (2.49 g/100 g), supported fermentation by both strains. F-19 and BB-12 lowered pH, with F-19 showing stronger acidification, and maintained high viability (8.85-8.90 log CFU/mL). Fermentation altered sugar profiles and produced unique volatile compounds, enhancing aroma and sensory attributes. F-19 generated 2-phenylethanol, a unique flavor compound, absent in BB-12. Phenolic content initially increased but antioxidant activity decreased during storage. Betacyanin remained stable for up to 14 days. Red pitaya improved F-19 viability through the simulated GIT, while BB-12 populations significantly decreased (p < 0.05). These results suggest red pitaya pulp is a promising plant-based matrix for F-19, offering protection during digestion and highlighting its potential as a functional food with enhanced bioactive compound bioavailability and sensory attributes.PMID:39147472 | DOI:10.1016/j.foodres.2024.114820
A systematic review of the gut microbiome, metabolites, and multi-omics biomarkers across the colorectal cancer care continuum
Benef Microbes. 2024 Aug 14:1-25. doi: 10.1163/18762891-bja00026. Online ahead of print.ABSTRACTThe gut microbiome and the microbial metabolome contribute to treatment efficacy and treatment outcomes across the cancer care spectrum. This study systematically reviewed the existing literature between 2007 to March 2022 to elucidate the role of gut microbiota-metabolite biomarkers in colorectal cancer (CRC) care and treatment-related outcomes. Using Covidence, all studies identified were screened by title and abstract, followed by a full-text review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and data extraction. We analysed 13 non-experimental and 9 experimental CRC studies and found that, usually, the α-diversity of the gut microbiome and short-chain fatty acids decreased in CRC patients, while amino acids (e.g. glutamate) increased in CRC patients. Correlations between specific gut microbial taxa and metabolites were identified, with amino acids, fatty acids, and glycerol positively associated with certain gut microbes. Interventions promoting gut microbes and microbial metabolites associated with better health outcomes (e.g. Bifidobacterium, Lactobacillus, butyric acid, and bile acid) can potentially promote treatment efficacy and improve cancer care outcomes. Gut microbial metabolism should be integrated into targeted cancer interventions for CRC patients, given the confirmed role of the gut microbiome and metabolome pathways across the CRC care continuum.PMID:39147373 | DOI:10.1163/18762891-bja00026
Radix Isatidis polysaccharide (RIP) alleviates QX-genotype infectious bronchitis virus-induced interstitial nephritis through the Nrf2/NLRP3/Caspase-3 signaling pathway
Int J Biol Macromol. 2024 Aug 13:134571. doi: 10.1016/j.ijbiomac.2024.134571. Online ahead of print.ABSTRACTInterstitial nephritis is the primary cause of mortality in IBV-infected chickens. Our previous research has demonstrated that Radix Isatidis polysaccharide (RIP) could alleviate this form of interstitial nephritis. To explore the mechanism, SPF chickens and chicken embryonic kidney cells (CEKs) were pre-treated with RIP and subsequently infected with QX-genotype IBV strain. Kidneys were sampled for transcriptomic and metabolomic analyses, and the cecum contents were collected for 16S rRNA gene sequencing. Results showed that pre-treatment with RIP led to a 50 % morbidity reduction in infected-chickens, along with decreased tissue lesion and viral load in the kidneys. Multi-omics analysis indicated three possible pathways (including antioxidant, anti-inflammatory and anti-apoptosis) which associated with RIP's efficacy against interstitial nephritis. Following further validation both in vivo and in vitro, the results showed that pre-treatment with RIP could activate the antioxidant transcription factor Nrf2, stimulate antioxidant enzyme expression, and consequently inhibit oxidative stress. Pre-treatment with RIP could also significantly reduce the expression of NLRP3 inflammasome and apoptosis-associated proteins (including Bax, Caspase-3, and Caspase-9). Additionally, RIP was also observed to promote the growth of beneficial bacteria in the intestine. Overall, pretreatment with RIP can alleviate QX-genotype IBV-induced interstitial nephritis via the Nrf2/NLRP3/Caspase-3 signaling pathway. This study lays the groundwork for the potential use of RIP in controlling avian infectious bronchitis (IB).PMID:39147344 | DOI:10.1016/j.ijbiomac.2024.134571
Melatonin alleviates brain injury in copper-laden rats: Underlying benefits for Wilson's disease
Biochem Pharmacol. 2024 Aug 13:116490. doi: 10.1016/j.bcp.2024.116490. Online ahead of print.ABSTRACTCopper serves as an indispensable cofactor for all living organisms, and its excessive accumulation has been associated with a variety of diseases. Wilson's disease (WD) serves as an illustrative example of copper toxicity in humans, frequently presenting with liver and/or neuropsychiatric symptoms. The current therapeutic drugs, penicillamine (PA) and zinc gluconate (ZnG), have constraints, and research on their combination efficacy remains insufficient. It has been reported that melatonin (MLT) plays a vital role in binding to transition metals and exhibits strong antioxidant capacity. To investigate the therapeutic efficacy of MLT and combined treatment, rats were randomly divided into the following seven groups: the control (Con) group, copper-laden model rat (Mod) group, PA-treated group, ZnG-treated group, MLT- treated group, PA-ZnG-treated group, and PA-MLT-treated group. Then potential mechanisms and targets were investigated using a combination of metabolomics and network pharmacology and verified by molecular docking and qPCR. The findings revealed that MLT and the combination significantly improved behavior, pathology and copper levels in copper-laden rats. The results of the metabolomics study showed that profoundly altered metabolites were identified, and alanine, aspartate and glutamate metabolism, pyruvate metabolism, citrate cycle (TCA cycle), and glycolysis/gluconeogenesis were explored. In addition, molecular docking showed that MLT had high binding affinity with key targets, and qPCR results revealed that MLT could reverse the mRNA expression of targets GOT2 and PKM2. It was concluded that MLT effectively improves brain injury in copper-laden rats, and this effect was linked with the altered features of the metabolite profiles.PMID:39147330 | DOI:10.1016/j.bcp.2024.116490
HSP60 chaperone deficiency disrupts the mitochondrial matrix proteome and dysregulates cholesterol synthesis
Mol Metab. 2024 Aug 13:102009. doi: 10.1016/j.molmet.2024.102009. Online ahead of print.ABSTRACTOBJECTIVE: Mitochondrial proteostasis is critical for cellular function. The molecular chaperone HSP60 is essential for cell function and dysregulation of HSP60 expression has been implicated in cancer and diabetes. The few reported patients carrying HSP60 gene variants show neurodevelopmental delay and brain hypomyelination. Hsp60 interacts with more than 260 mitochondrial proteins but the mitochondrial proteins and functions affected by HSP60 deficiency are poorly characterized.METHODS: We studied two model systems for HSP60 deficiency: (1) engineered HEK cells carrying an inducible dominant negative HSP60 mutant protein, (2) zebrafish HSP60 knockout larvae. Both systems were analyzed by RNASeq, proteomics, and targeted metabolomics, and several functional assays relevant for the respective model. In addition, skin fibroblasts from patients with disease-associated HSP60 variants were analyzed by proteomics.RESULTS: We show that HSP60 deficiency leads to a differentially downregulated mitochondrial matrix proteome, transcriptional activation of stress responses, and dysregulated cholesterol biosynthesis. This leads to lipid accumulation in zebrafish knockout larvae.CONCLUSIONS: Our data provide a compendium of the effects of HSP60 deficiency on the mitochondrial matrix proteome. We show that HSP60 is a master regulator and modulator of mitochondrial functions and metabolic pathways. HSP60 dysfunction also affects cellular metabolism and disrupts the integrated stress response. The effect on cholesterol synthesis explains the effect of HSP60 dysfunction on myelination observed in patients carrying genetic variants of HSP60.PMID:39147275 | DOI:10.1016/j.molmet.2024.102009
Encapsulation of photosensitizer worsen cell responses after photodynamic therapy protocol and polymer micelles act as biomodulators on their own
Int J Pharm. 2024 Aug 13:124589. doi: 10.1016/j.ijpharm.2024.124589. Online ahead of print.ABSTRACTPhotodynamic therapy (PDT) is a photochemical therapeutic modality used clinically for dermatological, ophthalmological and oncological applications. Pheo a was used as a model photosensitizer, either in its free form or encapsulated within poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) polymer micelles. Block copolymer micelles are water-soluble biocompatible nanocontainers with great potential for delivering hydrophobic drugs. Empty PEO-PCL micelles were also tested throughout the experiments. The goal was to conduct an in vitro investigation into human colorectal tumor HCT-116 cellular responses induced by free and encapsulated Pheo a in terms of cell architecture, plasma membrane exchanges, mitochondrial function, and metabolic disturbances. In a calibrated PDT protocol, encapsulation enhanced Pheo a penetration (flow cytometry, confocal microscopy) and cell death (Prestoblue assay), causing massive changes to cell morphology (SEM) and cytoskeleton organization (confocal), mitochondrial dysfunction and loss of integrity (TEM), rapid and massive ion fluxes across the plasma membrane (ICP-OES, ion chromatography), and metabolic alterations, including increased levels of amino acids and choline derivatives (1H NMR). The detailed investigation provides insights into the multifaceted effects of encapsulated Pheo-PDT, emphasizing the importance of considering both the photosensitizer and its delivery system in understanding therapeutic outcomes. The study also raises questions as to the broader impact of empty nanovectors per se, and encourages a more comprehensive exploration of their biological effects.PMID:39147251 | DOI:10.1016/j.ijpharm.2024.124589
Landscapes of maternal and neonatal gut microbiome and plasma metabolome signatures and their interaction in gestational diabetes mellitus
J Nutr Biochem. 2024 Aug 13:109716. doi: 10.1016/j.jnutbio.2024.109716. Online ahead of print.ABSTRACTBACKGROUND: Gestational diabetes mellitus (GDM) is prevalent among pregnant individuals and is linked to increased risks for both mothers and foetuses. Although GDM is known to cause disruptions in gut microbiota and metabolites, their potential transmission to the foetus has not been fully explored. This study aimed to characterize the similarities in microbial and metabolic signatures between mothers with GDM and their neonates as well as the interactions between these signatures.METHODS: This study included 89 maternal-neonate pairs (44 in the GDM group and 45 in the normoglycaemic group). We utilized 16S rRNA gene sequencing and untargeted metabolomics to analyse the gut microbiota and plasma metabolomics of mothers and neonates. Integrative analyses were performed to elucidate the interactions between these omics.RESULTS: Distinct microbial and metabolic signatures were observed in GDM mothers and their neonates compared to those in the normoglycaemic group. Fourteen genera showed similar alterations across both groups. Metabolites linked to glucose, lipid, and energy metabolism were differentially influenced in GDM, with similar trends observed in both mothers and neonates in the GDM group. Network analysis indicated significant associations between Qipengyuania and metabolites related to bile acid metabolism in mothers and newborns. Furthermore, we observed a significant correlation between several genera and metabolites and clinical phenotypes in normoglycaemic mothers and newborns, but these correlations were disrupted in the GDM group.CONCLUSION: Our findings suggest that GDM consistently affects both the microbiota and metabolome in mothers and neonates, thus elucidating the mechanism underlying metabolic transmission across generations. These insights contribute to knowledge regarding the multiomics interactions in GDM and underscore the need to further investigate the prenatal environmental impacts on offspring metabolism.PMID:39147246 | DOI:10.1016/j.jnutbio.2024.109716
Altered purine and pentose phosphate pathway metabolism in uteroplacental insufficiency-induced intrauterine growth restriction offspring rats impairs intestinal function
J Nutr Biochem. 2024 Aug 13:109737. doi: 10.1016/j.jnutbio.2024.109737. Online ahead of print.ABSTRACTBACKGROUND: This study aimed to identify metabolic alterations in the small intestine of newborn rats with intrauterine growth restriction (IUGR), a condition linked to intestinal dysfunction.METHODS: Pregnant Sprague Dawley rats underwent bilateral uterine artery ligation on gestational day 17 to induce intrauterine growth restriction or sham surgery. Rat pups were delivered spontaneously on gestational day 22. Small intestine tissues were collected on postnatal days 0 and 7 from offspring. Liquid chromatography-mass spectrometry analysis was performed to investigate untargeted metabolomic profiles. Western blot analysis assessed protein expression of key regulators.RESULTS: Newborn rats with intrauterine growth restriction exhibited distinct small intestine metabolic profiles compared to controls on postnatal day 0. Notably, significant alterations were observed in purine metabolism, the pentose phosphate pathway, and related pathways. Western blot analysis revealed a decrease expression in transketolase, a key enzyme of the pentose phosphate pathway, suggesting impaired activity of the pentose phosphate pathway. Additionally, decreased expression of tight junction proteins ZO-1 and occludin indicated compromised intestinal barrier function in rats with intrauterine growth restriction. Similar metabolic disruptions persisted on postnatal day 7, with further reductions in tricarboxylic acid cycle intermediates and folate biosynthesis precursors. Interestingly, lysyl-glycine, a protein synthesis marker, was elevated in rats with intrauterine growth restriction.CONCLUSIONS: Our findings reveal a distinct metabolic signature in the small intestine of neonatal rats with intrauterine growth restriction, characterized by disruptions in the pentose phosphate pathway, purine metabolism, and energy production pathways. These novel insights suggest potential mechanisms underlying IUGR-associated intestinal dysfunction and impaired growth.PMID:39147244 | DOI:10.1016/j.jnutbio.2024.109737
Metabolomics to investigate the effect of preconditioned mesenchymal stem cells with crocin on pulmonary epithelial cells exposed to 2-chloroethyl ethyl sulfide
J Proteomics. 2024 Aug 13:105280. doi: 10.1016/j.jprot.2024.105280. Online ahead of print.ABSTRACTMetabolomics significantly impacts drug discovery and precise disease management. This study meticulously assesses the metabolite profiles of cells treated with Crocin, Dexamethasone, and mesenchymal stem cells (MSCs) under oxidative stress induced by 2-chloroethyl ethyl sulfide (CEES). Gas chromatography/mass spectrometry (GC/MS) analysis unequivocally identified substantial changes in 37 metabolites across the treated groups. Notably, pronounced alterations were observed in pathways associated with aminoacyl-tRNA biosynthesis and the metabolism of aspartate, serine, proline, and glutamate. These findings demonstrate the potent capacity of the analyzed treatments to effectively reduce inflammation, mitigate reactive oxygen species production, and enhance cell survival rates. SIGNIFICANCE.PMID:39147238 | DOI:10.1016/j.jprot.2024.105280
Intestinal dysbacteriosis contributes to persistent cognitive impairment after resolution of acute liver failure
Am J Pathol. 2024 Aug 13:S0002-9440(24)00287-6. doi: 10.1016/j.ajpath.2024.07.014. Online ahead of print.ABSTRACTRegulating the gut microbiota alleviates hepatic encephalopathy (HE). It remains unclear whether it is imperative to withhold treatment for microbial imbalance after liver functional recovery. This work aims to elucidate the alterations in cognitive behavior, liver function, synaptic transmission, and brain metabolites in acute liver failure(ALF) mice before and after hepatic function recovery. Here, thioacetamide was injected intraperitoneally to establish an ALF mouse model, which induced HE. By performing hierarchical clustering analysis, we found that the liver functions normalized, but cognitive dysfunction and intestinal dysbacteriosis were found in the ALF mice 14 days after thioacetamide injection. Additionally, fecal microbiota transplant from the ALF mice with liver function recovery could induce liver injury and cognitive impairment. Moreover, we found alterations in synaptic transmission in the ALF mice with liver function improvement, and the correlations between the gut bacteria and synaptic transmission in the cortex were significant. Finally, we detected apparent alterations in the brain metabolic profiles of the ALF mice after liver function improvement by performing 1H nuclear magnetic resonance spectroscopy, suggesting a risk of HE. These results showed that intestinal dysbacteriosis in ALF mice with liver function recovery is sufficient to induce liver injury and cognitive impairment. These results indicated continuous care may be necessary for monitoring microbial imbalance even in ALF-induced HE patients whose liver function has recovered significantly.PMID:39147234 | DOI:10.1016/j.ajpath.2024.07.014
Dysregulated Metabolic Pathways Associated with Air Pollution Exposure and the Risk of Autism: Evidence from Epidemiological Studies
Environ Pollut. 2024 Aug 13:124729. doi: 10.1016/j.envpol.2024.124729. Online ahead of print.ABSTRACTAutism spectrum disorder (ASD) is a developmental disorder with symptoms that range from social and communication impairments to restricted interests and repetitive behavior and is the 4th most disabling condition for children aged 5-14. Risk factors of ASD are not fully understood. Environmental risk factors are believed to play a significant role in the ASD epidemic. Research focusing on air pollution exposure as an early-life risk factor of autism is growing, with numerous studies finding associations of traffic and industrial emissions with an increased risk of ASD. One of the possible mechanisms linking autism and air pollution exposure is metabolic dysfunction. However, there were no consensus about the key metabolic pathways and corresponding metabolite signatures in mothers and children that are altered by air pollution exposure and cause the ASD. Therefore, we performed a review of published papers examining the metabolomic signatures and metabolic pathways that are associated with either air pollution exposure or ASD risk in human studies. In conclusion, we found that dysregulated lipid, fatty acid, amino acid, neurotransmitter, and microbiome metabolisms are associated with both short-term and long-term air pollution exposure and the risk of ASD. These dysregulated metabolisms may provide insights into ASD etiology related to air pollution exposure, particularly during the perinatal period in which neurodevelopment is highly susceptible to damage from oxidative stress and inflammation.PMID:39147228 | DOI:10.1016/j.envpol.2024.124729
Circulating Metabolomics Revealed Novel Associations between Multiple Ambient Air Pollutants Exposure and Chronic Obstructive Pulmonary Disease Incidence: Evidence from A Prospective Cohort Study
Environ Pollut. 2024 Aug 13:124727. doi: 10.1016/j.envpol.2024.124727. Online ahead of print.ABSTRACTThe mechanisms underlying relationships between ambient air pollution and chronic obstructive pulmonary disease (COPD) risk remained largely uncertain. In this study, we aim to evaluate whether metabolic signature comprising multiple circulating metabolites can characterize metabolic response to the multiple air pollution; and to assess whether the identified metabolic signature contribute to COPD risk. A total of 227,962 participants with complete data were included from the UK biobank study. Concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), and particulate matter (PM2.5 and PM10) were evaluated by land-use regression models. We newly computed an air pollution score to reflect joint exposure to multiple air pollutants. Circulating metabolome was quantified by nuclear magnetic resonance (NMR) spectroscopy. During a median of 12.78 years of follow-up, a total of 8,685 incident COPD cases were documented. After multiple correction, the Cox regression models showed that 102 of 143 metabolites were significantly associated with COPD risk. Utilizing elastic net regularized regressions, we identified a metabolic signature comprising 106 metabolites (including lipid, fatty acids, glycolysis and amino acids et al.) were robustly related to air pollution score. In the multivariate-adjusted Cox regression models, the derived metabolic signature showed a positive correlation with incident COPD [HR per SD =1.20 (95% CI: 1.17-1.22)]. Casual mediation analysis further noted that the constructed metabolic signature mediated 10.5 % (8.3%-13.1%) of the air pollution-COPD associations. Taken together, our findings identified a metabolic signature that captured metabolic response to various air pollutants exposure jointly, and predicted future COPD risk independent of known risk factors.PMID:39147227 | DOI:10.1016/j.envpol.2024.124727
Bacillus subtilis JATP3 improved the immunity of weaned piglets by improving intestinal flora and producing Citalopram
Microb Pathog. 2024 Aug 13:106852. doi: 10.1016/j.micpath.2024.106852. Online ahead of print.ABSTRACTThe purpose of this study was to evaluate the ability of Bacillus subtilis JATP3 to stimulate immune response and improve intestinal health in piglets during the critical weaning period. Twelve 28-day-old weaned piglets were randomly divided into two groups. One group was fed a basal diet, while the other group was fed a basal diet supplemented with B. subtilis JATP3 (1 × 109 CFU/mL; 10 mL) for 28 days. The results revealed a significant increase in the intestinal villus gland ratio of weaned piglets following the inclusion of B. subtilis JATP3 (P < 0.05). Inclusion of a probiotic supplement improve the intestinal flora of jejunum and ileum of weaned piglets. Metabolomics analysis demonstrated a notable rise in citalopram levels in the jejunum and ileum, along with elevated levels of isobutyric acid and isocitric acid in the ileum. The results of correlation analysis show that indicated a positive correlation between citalopram and microbial changes. Furthermore, the probiotic-treated group exhibited a significant upregulation in the relative expression of Claudin, Zonula Occludens 1 (ZO-1), and Interleukin 10 (IL-10) in the jejunum and ileum, while displaying a noteworthy reduction in the relative expression of Interleukin 1β (IL-1β). Overall, these findings suggest that B. subtilis JATP3 can safeguard intestinal health by modulating the structure of the intestinal microbiota and their metabolites, wherein citalopram might be a key component contributing to the therapeutic effects of B. subtilis JATP3.PMID:39147213 | DOI:10.1016/j.micpath.2024.106852