Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Successful combination of benchtop nuclear magnetic resonance spectroscopy and chemometric tools: A review

Sun, 09/07/2023 - 12:00
Anal Chim Acta. 2023 Sep 8;1273:341495. doi: 10.1016/j.aca.2023.341495. Epub 2023 Jun 6.ABSTRACTLow-field nuclear magnetic resonance (NMR) has three general modalities: spectroscopy, imaging, and relaxometry. In the last twelve years, the modality of spectroscopy, also known as benchtop NMR, compact NMR, or just low-field NMR, has undergone instrumental development due to new permanent magnetic materials and design. As a result, benchtop NMR has emerged as a powerful analytical tool for use in process analytical control (PAC). Nevertheless, the successful application of NMR devices as an analytical tool in several areas is intrinsically linked to its coupling with different chemometric methods. This review focuses on the evolution of benchtop NMR and chemometrics in chemical analysis, including applications in fuels, foods, pharmaceuticals, biochemicals, drugs, metabolomics, and polymers. The review also presents different low-resolution NMR methods for spectrum acquisition and chemometric techniques for calibration, classification, discrimination, data fusion, calibration transfer, multi-block and multi-way.PMID:37423658 | DOI:10.1016/j.aca.2023.341495

HKDC1 reprograms lipid metabolism to enhance gastric cancer metastasis and cisplatin resistance via forming a ribonucleoprotein complex

Sun, 09/07/2023 - 12:00
Cancer Lett. 2023 Jul 7:216305. doi: 10.1016/j.canlet.2023.216305. Online ahead of print.ABSTRACTAs essential modulators of transcription and translation, RNA-binding proteins (RBPs) are frequently dysregulated in cancer. Bioinformatics study reveals that the RNA-binding protein hexokinase domain component 1 (HKDC1) is overexpressed in gastric cancer (GC). As HKDC1 plays a role in lipid homeostasis in the liver and glucose metabolism in certain cancers, the exact mechanism of action of HKDC1 in GC remains largely unknown. Upregulation of HKDC1 correlates with chemoresistance and poor prognosis in GC patients. HKDC1 enhances invasion, migration and resistance to cisplatin (CDDP) in GC cells in vitro and in vivo. Comprehensive transcriptomic sequencing and metabolomic analysis reveal that HKDC1 mediates abnormal lipid metabolism in GC cells. Herein, we identify a number of HKDC1-binding endogenous RNAs in GC cells, including protein kinase, DNA-activated, catalytic subunit (PRKDC) mRNA. We further validate that PRKDC is a crucial downstream effector of HKDC1 induced-GC tumorigenesis depends on lipid metabolism. Interestingly, G3BP1, a well-known oncoprotein, can be bound by HKDC1. HKDC1 cooperates with G3BP1 to enhance the stability of PRKDC transcript. Our results reveal a novel HKDC1/G3BP1-PRKDC regulatory axis that induces GC metastasis and chemoresistance via reprogramming lipid metabolism, which may provide an effective therapeutic strategy for a subset of GC with HKDC1 overexpression.PMID:37423558 | DOI:10.1016/j.canlet.2023.216305

Alterations of gut microbiota and its correlation with the liver metabolome in the process of ameliorating Parkinson's disease with Buyang Huanwu decoction

Sun, 09/07/2023 - 12:00
J Ethnopharmacol. 2023 Jul 7:116893. doi: 10.1016/j.jep.2023.116893. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu decoction (BHD), a famous traditional Chinese medicine (TCM) formula, was first recorded in Qing Dynasty physician Qingren Wang's Yi Lin Gai Cuo. BHD has been widely utilized in the treatment of patients with neurological disorders, including Parkinson's disease (PD). However, the underlying mechanism has not been fully elucidated. In particular, little is known about the role of gut microbiota.AIM OF THE STUDY: We aimed to reveal the alterations and functions of gut microbiota and its correlation with the liver metabolome in the process of improving PD with BHD.MATERIALS AND METHODS: The cecal contents were collected from PD mice treated with or without BHD. 16S rRNA gene sequencing was performed on an Illumina MiSeq-PE250 platform, and the ecological structure, dominant taxa, co-occurrence patterns, and function prediction of the gut microbial community were analyzed by multivariate statistical methods. The correlation between differential microbial communities in the gut and differentially accumulated metabolites in the liver was analyzed using Spearman's correlation analysis.RESULTS: The abundance of Butyricimonas, Christensenellaceae, Coprococcus, Peptococcaceae, Odoribacteraceae, and Roseburia was altered significantly in the model group, which was by BHD. Ten genera, namely Dorea, unclassified_Lachnospiraceae, Oscillospira, unidentified_Ruminococcaceae, unclassified_Clostridiales, unidentified_Clostridiales, Bacteroides, unclassified_Prevotellaceae, unidentified_Rikenellaceae, and unidentified_S24-7, were identified as key bacterial communities. According to the function prediction of differential genera, the mRNA surveillance pathway might be a target of BHD. Integrated analysis of gut microbiota and the liver metabolome revealed that several gut microbiota genera such as Parabacteroides, Ochrobactrum, Acinetobacter, Clostridium, and Halomonas, were positively or negatively correlated with some nervous system-related metabolites, such as L-carnitine, L-pyroglutamic acid, oleic acid, and taurine.CONCLUSIONS: Gut microbiota might be a target of BHD in the process of ameliorating PD. Our findings provide novel insight into the mechanisms underlying the effects of BHD on PD and contribute to the development of TCM.PMID:37423520 | DOI:10.1016/j.jep.2023.116893

The growth inhibitory effects and non-targeted metabolomic profiling of Microcystis aeruginosa treated by Scenedesmus sp

Sun, 09/07/2023 - 12:00
Chemosphere. 2023 Jul 7:139446. doi: 10.1016/j.chemosphere.2023.139446. Online ahead of print.ABSTRACTThe health of the aquatic ecosystem has recently been severely affected by cyanobacterial blooms brought on by eutrophication. Therefore, it is critical to develop efficient and secure methods to control dangerous cyanobacteria, such as Microcystis aeruginosa. In this research, we tested the inhibition of M. aeruginosa growth by a Scenedesmus sp. strain isolated from a culture pond. Scenedesmus sp. culture filtrate that had been lyophilized was added to M. aeruginosa, and cultivation for seven days, the cell density, chlorophyll a (Chl-a) concentration, maximum quantum yield of photosystem II (Fv/Fm), the activities of superoxide dismutase (SOD), catalase (CAT), and the concentration of malondialdehyde (MDA) and glutathione (GSH) were measured. Moreover, non-targeted metabolomics was carried out to provide light on the inhibitory mechanism in order to better understand the metabolic response. According to the results, M. aeruginosa is effectively inhibited by the lyophilized Scenedesmus sp. culture filtrate at a rate of 51.2%. Additionally, the lyophilized Scenedesmus sp. clearly inhibit the photosystem and damages the antioxidant defense system of M. aeruginosa cells, resulting in oxidative damage, which worsens membrane lipid peroxidation, according to changes in Chl-a, Fv/Fm, SOD, CAT enzyme activities and MDA, GSH. Metabolomics analysis revealed that the secondary metabolites of Scenedesmus sp. significantly interfere with the metabolism of M. aeruginosa involved in amino acid synthesis, membrane creation and oxidative stress, which is coherent with the morphology and physiology outcomes. These results demonstrate that the secondary metabolites of Scenedesmus sp. exert algal inhibition effect by breaked the membrane structure, destroyed the photosynthetic system of microalgae, inhibited amino acid synthesis, reduced antioxidant capacity, and eventually caused algal cell lysis and death. Our research provides a reliable basis for the biological control of cyanobacterial blooms on the one hand, and on other hand supply application of non-targeted metabolome on the study of microalgae allelochemicals.PMID:37423414 | DOI:10.1016/j.chemosphere.2023.139446

Gut microbiota disorder induces liver dysfunction in polycystic ovary syndrome rats' model by regulating metabolite rosmarinic acid

Sun, 09/07/2023 - 12:00
Life Sci. 2023 Jul 7:121912. doi: 10.1016/j.lfs.2023.121912. Online ahead of print.ABSTRACTAIMS: The present study aims to investigate the impact of the gut microbiota and serum metabolites on the regulation of liver dysfunction in PCOS.MATERIALS AND METHODS: PCOS rat models were established by treating Sprague Dawley (SD) rats with DHEA (an androgen, 60 mg/kg) and LET (a nonsteroidal aromatase inhibitor, 1 mg/kg) for 90 days. Hematoxylin and eosin staining (H&E), Western blotting, and radioimmunoassay were employed to test ovarian and liver functions. Gut microbiome and serum metabolites were assessed using 16S rRNA amplicon sequencing and non-targeted metabolomics, respectively. The association between gut microbiota and serum metabolites was examined using Spearman analysis. Finally, using HepG2 cells to investigate the function of the serum metabolite rosmarinic acid (RA).KEY FINDINGS: Both Dehydroepiandrosterone (DHEA) and letrozole (LET) treatments induced a PCOS phenotype and liver dysfunction. However, LET resulted in more severe lipid accumulation and liver cell apoptosis than DHEA. 16S rRNA sequencing and non-targeted metabolomics analysis revealed significant differences in beta diversity and serum metabolite profiles among the three groups. Furthermore, among the significantly changed metabolites, RA was found to have a significant correlation with the levels of serum aspartate transaminase (AST) and lactate dehydrogenase (LDH) and could promote HepG2 cell apoptosis.SIGNIFICANCE: Restoring gut microbiota, altering serum metabolites and/or decreasing RA may provide a new insight to treat this complication.PMID:37423380 | DOI:10.1016/j.lfs.2023.121912

Bioaccumulation and molecular effects of carbamazepine and methylmercury co-exposure in males of Dreissena polymorpha

Sun, 09/07/2023 - 12:00
Sci Total Environ. 2023 Jul 7:165379. doi: 10.1016/j.scitotenv.2023.165379. Online ahead of print.ABSTRACTDreissena polymorpha is a bivalve promising for biomonitoring in freshwater ecosystems thanks to its abundance and high filtration activity allowing rapid uptake of toxicants and identification of their negative effects. Nonetheless, we still lack knowledge on its molecular responses to stress under realistic scenario, e.g. multi-contamination. Carbamazepine (CBZ) and Hg are ubiquitous pollutants sharing molecular toxicity pathways, e.g. oxidative stress. A previous study in zebra mussels showed their co-exposure to cause more disturbing alterations than single exposures, but molecular toxicity pathways remained unidentified. D. polymorpha was exposed 24 h (T24) and 72 h (T72) to CBZ (6.1 ± 0.1 μg L-1), MeHg (430 ± 10 ng L-1) and the co-exposure (6.1 ± 0.1 μg L-1CBZ and 500 ± 10 ng L-1 MeHg) at concentrations representative of polluted areas (~10× EQS). RedOx system at the gene and enzyme level, the proteome and the metabolome were compared. The co-exposure resulted in 108 differential abundant proteins (DAPs), as well as 9 and 10 modulated metabolites at T24 and T72, respectively. The co-exposure specifically modulated DAPs and metabolites involved in neurotransmission, e.g. dopaminergic synapse and GABA. CBZ specifically modulated 46 DAPs involved in calcium signaling pathways and 7 amino acids at T24. MeHg specifically modulated 55 DAPs proteins involved in the cytoskeleton remodeling and hypoxia-induced factor 1 pathway, without altering the metabolome. Single and co-exposures commonly modulated proteins and metabolites involved in energy and amino acid metabolisms, response to stress and development. Concomitantly, lipid peroxidation and antioxidant activities were unchanged, supporting that D. polymorpha tolerated experimental conditions. The co-exposure was confirmed to cause more alterations than single exposures. This was attributed to the combined toxicity of CBZ and MeHg. Altogether, this study underlined the necessity to better characterize molecular toxicity pathways of multi-contamination that are not predictable on responses to single exposures, to better anticipate adverse effects in biota and improve risk assessment.PMID:37423277 | DOI:10.1016/j.scitotenv.2023.165379

Role of metabolomics in the delivery of precision nutrition

Sun, 09/07/2023 - 12:00
Redox Biol. 2023 Jul 5;65:102808. doi: 10.1016/j.redox.2023.102808. Online ahead of print.ABSTRACTPrecision nutrition aims to deliver personalised dietary advice to individuals based on their personal genetics, metabolism and dietary/environmental exposures. Recent advances have demonstrated promise for the use of omic technologies for furthering the field of precision nutrition. Metabolomics in particular is highly attractive as measurement of metabolites can capture information on food intake, levels of bioactive compounds and the impact of diets on endogenous metabolism. These aspects contain useful information for precision nutrition. Furthermore using metabolomic profiles to identify subgroups or metabotypes is attractive for the delivery of personalised dietary advice. Combining metabolomic derived metabolites with other parameters in prediction models is also an exciting avenue for understanding and predicting response to dietary interventions. Examples include but not limited to role of one carbon metabolism and associated co-factors in blood pressure response. Overall, while evidence exists for potential in this field there are also many unanswered questions. Addressing these and clearly demonstrating that precision nutrition approaches enable adherence to healthier diets and improvements in health will be key in the near future.PMID:37423161 | DOI:10.1016/j.redox.2023.102808

IgG N-glycans are associated with prevalent and incident complications of type 2 diabetes

Sun, 09/07/2023 - 12:00
Diabetes Metab Res Rev. 2023 Jul 9:e3685. doi: 10.1002/dmrr.3685. Online ahead of print.ABSTRACTAIMS/HYPOTHESIS: Inflammation is important in the development of type 2 diabetes complications. The N-glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N-glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N-glycosylation of IgG may be related to the development of complications of type 2 diabetes.METHODS: In three independent type 2 diabetes cohorts, plasma IgG N-glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N-glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox- and logistic regression, followed by meta-analyses. The models were adjusted for age and sex and additionally for clinical risk factors.RESULTS: IgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex.CONCLUSIONS: We showed that IgG N-glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro- and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N-glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions.PMID:37422864 | DOI:10.1002/dmrr.3685

Gut microbiota-derived tryptophan metabolites alleviate liver injury via AhR/Nrf2 activation in pyrrolizidine alkaloids-induced sinusoidal obstruction syndrome

Sat, 08/07/2023 - 12:00
Cell Biosci. 2023 Jul 8;13(1):127. doi: 10.1186/s13578-023-01078-4.ABSTRACTBACKGROUND AND AIMS: Hepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury, such as pyrrolizidine alkaloids, to the liver sinusoidal endothelial cells, and the gut microbiota may be involved. However, the specific role and underlying mechanism of gut microbiota in HSOS is unknown.METHODS: HSOS model was established by gavage of monocrotaline (MCT) in rats. Fecal microbiota transplantation (FMT) with HSOS-derived or healthy gut flora was also conducted to validate the role of gut microflora in MCT-induced liver injury. The microbial 16 s rRNA analysis and untargeted metabolomics analysis in the faeces were performed to identify HSOS-related flora and metabolites. Finally, by supplementation with specific tryptophan metabolites, such as indole-3-acetaldehyde (IAAld) and indole acetic acid (IAA), we further confirmed the role of tryptophan metabolism in HSOS and the role of the AhR/Nrf2 pathway in MCT-induced liver injury.RESULTS: MCT induced HSOS-like liver injury in rats with significantly altered gut microbiota. Particularly, some tryptophan-metabolizing bacteria reduced in MCT-treated rats, such as Bacteroides, Bifidobacterium, Lactobacillus and Clostridium, and accompanied by a decrease in microbial tryptophan metabolic activity and a series of tryptophan derivatives. Restoring the gut microbiota via FMT improved MCT-induced liver damage, while HSOS-derived gut microbiota aggravated the liver injury induced by MCT. Supplementation with microbial tryptophan derivatives (IAAld or IAA), or 6-formylindolo(3,2-b)carbazole (Ficz, an AhR agonist) could activate the AhR/Nrf2 signaling pathway, thereby attenuating the MCT-induced liver oxidative stress and liver sinusoidal endothelial cells injury.CONCLUSIONS: Gut microbiota plays a critical role in MCT-induced HSOS, with inadequate microbial tryptophan metabolism in the gut and consequently a lower activity of the AhR/Nrf2 signaling pathway in the liver, which should be a potential target for the management of HSOS.PMID:37422682 | DOI:10.1186/s13578-023-01078-4

Targeted metabolomic profiling as a tool for diagnostics of patients with non-small-cell lung cancer

Sat, 08/07/2023 - 12:00
Sci Rep. 2023 Jul 8;13(1):11072. doi: 10.1038/s41598-023-38140-7.ABSTRACTLung cancer is referred to as the second most common cancer worldwide and is mainly associated with complex diagnostics and the absence of personalized therapy. Metabolomics may provide significant insights into the improvement of lung cancer diagnostics through identification of the specific biomarkers or biomarker panels that characterize the pathological state of the patient. We performed targeted metabolomic profiling of plasma samples from individuals with non-small cell lung cancer (NSLC, n = 100) and individuals without any cancer or chronic pathologies (n = 100) to identify the relationship between plasma endogenous metabolites and NSLC by means of modern comprehensive bioinformatics tools, including univariate analysis, multivariate analysis, partial correlation network analysis and machine learning. Through the comparison of metabolomic profiles of patients with NSCLC and noncancer individuals, we identified significant alterations in the concentration levels of metabolites mainly related to tryptophan metabolism, the TCA cycle, the urea cycle and lipid metabolism. Additionally, partial correlation network analysis revealed new ratios of the metabolites that significantly distinguished the considered groups of participants. Using the identified significantly altered metabolites and their ratios, we developed a machine learning classification model with an ROC AUC value equal to 0.96. The developed machine learning lung cancer model may serve as a prototype of the approach for the in-time diagnostics of lung cancer that in the future may be introduced in routine clinical use. Overall, we have demonstrated that the combination of metabolomics and up-to-date bioinformatics can be used as a potential tool for proper diagnostics of patients with NSCLC.PMID:37422585 | DOI:10.1038/s41598-023-38140-7

A comparison of different machine-learning techniques for the selection of a panel of metabolites allowing early detection of brain tumors

Sat, 08/07/2023 - 12:00
Sci Rep. 2023 Jul 8;13(1):11044. doi: 10.1038/s41598-023-38243-1.ABSTRACTMetabolomics combined with machine learning methods (MLMs), is a powerful tool for searching novel diagnostic panels. This study was intended to use targeted plasma metabolomics and advanced MLMs to develop strategies for diagnosing brain tumors. Measurement of 188 metabolites was performed on plasma samples collected from 95 patients with gliomas (grade I-IV), 70 with meningioma, and 71 healthy individuals as a control group. Four predictive models to diagnose glioma were prepared using 10 MLMs and a conventional approach. Based on the cross-validation results of the created models, the F1-scores were calculated, then obtained values were compared. Subsequently, the best algorithm was applied to perform five comparisons involving gliomas, meningiomas, and controls. The best results were obtained using the newly developed hybrid evolutionary heterogeneous decision tree (EvoHDTree) algorithm, which was validated using Leave-One-Out Cross-Validation, resulting in an F1-score for all comparisons in the range of 0.476-0.948 and the area under the ROC curves ranging from 0.660 to 0.873. Brain tumor diagnostic panels were constructed with unique metabolites, which reduces the likelihood of misdiagnosis. This study proposes a novel interdisciplinary method for brain tumor diagnosis based on metabolomics and EvoHDTree, exhibiting significant predictive coefficients.PMID:37422554 | DOI:10.1038/s41598-023-38243-1

Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling

Sat, 08/07/2023 - 12:00
NPJ Biofilms Microbiomes. 2023 Jul 8;9(1):47. doi: 10.1038/s41522-023-00415-2.ABSTRACTKnowledge gaps that limit the development of therapies for polycystic ovary syndrome (PCOS) concern various environmental factors that impact clinical characteristics. Circadian dysrhythmia contributes to glycometabolic and reproductive hallmarks of PCOS. Here, we illustrated the amelioration of Limosilactobacillus reuteri (L. reuteri) on biorhythm disorder-ignited dyslipidemia of PCOS via a microbiota-metabolite-liver axis. A rat model of long-term (8 weeks) darkness treatment was used to mimic circadian dysrhythmia-induced PCOS. Hepatic transcriptomics certified by in vitro experiments demonstrated that increased hepatic galanin receptor 1 (GALR1) due to darkness exposure functioned as a critical upstream factor in the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway to suppress nuclear receptors subfamily 1, group D, member 1 (NR1D1) and promoted sterol regulatory element binding protein 1 (SREBP1), inducing lipid accumulation in the liver. Further investigations figured out a restructured microbiome-metabolome network following L. reuteri administration to protect darkness rats against dyslipidemia. Notably, L. reuteri intervention resulted in the decrease of Clostridium sensu stricto 1 and Ruminococcaceae UCG-010 as well as gut microbiota-derived metabolite capric acid, which could further inhibit GALR1-NR1D1-SREBP1 pathway in the liver. In addition, GALR antagonist M40 reproduced similar ameliorative effects as L. reuteri to protect against dyslipidemia. While exogenous treatment of capric acid restrained the protective effects of L. reuteri in circadian disruption-induced PCOS through inhibiting GALR1-dependent hepatic lipid metabolism. These findings purport that L. reuteri could serve for circadian disruption-associated dyslipidemia. Manipulation of L. reuteri-capric acid-GALR1 axis paves way for clinical therapeutic strategies to prevent biorhythm disorder-ignited dyslipidemia in PCOS women.PMID:37422471 | DOI:10.1038/s41522-023-00415-2

Sinomenine ameliorates rheumatoid arthritis by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation

Sat, 08/07/2023 - 12:00
Sci Bull (Beijing). 2023 Jun 28:S2095-9273(23)00410-3. doi: 10.1016/j.scib.2023.06.027. Online ahead of print.ABSTRACTGut microbiota dysbiosis is associated with the development of rheumatoid arthritis (RA). Sinomenine (SIN) is an effective immunosuppressive and anti-inflammatory drug used for treating RA, but how SIN regulates gut microbiota to alleviate RA remains underexplored. To identify the critical gut microbial species and microbial metabolites associated with the RA-protective effects of SIN, the microbiota-dependent anti-RA effects of SIN were assessed by 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation. Metabolomics analysis, transcriptional analysis, and targeted bacteria/metabolites gavage were conducted to explore how SIN regulates gut microbiota to reduce the severity of RA. SIN could restore intestinal microbial balance by mainly modulating the abundance of Lactobacillus, and significantly relieve collagen-induced arthritis (CIA) symptoms in a gut microbiota-dependent manner. SIN significantly elevated microbial tryptophan metabolites indole-3-acrylic acid (IA), indole-3-propionic acid (IPA), and indole-3-acetic acid (IAA). Tryptophan metabolites supplementation could activate aryl hydrocarbon receptor (AhR) and regulate Th17/Treg balance in CIA rats. Intriguingly, SIN relieved the arthritis symptoms involving the enrichment of two beneficial anti-CIA Lactobacillus species, L. paracasei and L. casei by mono-colonization. The promising therapeutic function of SIN was mostly attributed to the activation of AhR by explicitly targeting the Lactobacillus and microbial tryptophan metabolites. The intestinal bacterium L. paracasei and L. casei may be used to reduce the severity of CIA.PMID:37422372 | DOI:10.1016/j.scib.2023.06.027

Comprehensive analysis of transcriptomic and metabolomic profiles uncovered the age-induced dynamic development pattern of subcutaneous fat in Ningxiang pig

Sat, 08/07/2023 - 12:00
Gene. 2023 Jul 6:147624. doi: 10.1016/j.gene.2023.147624. Online ahead of print.ABSTRACTEnhancing meat production and quality is the eternal theme for pig breeding industries. Fat deposition has always been the focus of research in practical production because it is closely linked to pig production efficiency and pork quality. In the current study, multi-omics techniques were performed to explore the modulatory mechanisms of backfat (BF) accumulation at three core developmental stages for Ningxiang pigs. Our results identify that 15 differentially expressed genes (DEGs) and 9 significantly changed metabolites (SCMs) contribute to the BF development via the cAMP signaling pathway, regulation of lipolysis in adipocytes, and biosynthesis of unsaturated fatty acids. Herein, we found a series of candidate genes such as adrenoceptor beta 1 (ADRB1), adenylate cyclase 5 (ADCY5), ATPase Na+/K+ transporting subunit beta 1 (ATP1B1), ATPase plasma membrane Ca2+ transporting 3 (ATP2B3), ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2), perilipin 1 (PLIN1), patatin like phospholipase domain containing 3 (PNPLA3), ELOVL fatty acid elongase 5 (ELOVL5) and metabolites like epinephrine, cAMP, arachidonic acid, oleic acid, linoleic acid, and docosahexaenoic acid exist age-specificeffects and play important roles in lipolysis, fat accumulation, and fatty acid composition. Our findings provide a reference for molecular mechanisms in BF tissue development and the optimization of carcass quality.PMID:37422178 | DOI:10.1016/j.gene.2023.147624

Comparative analysis of the difference in flavonoid metabolic pathway during coloring between red-yellow and red sweet cherry (Prunus avium L.)

Sat, 08/07/2023 - 12:00
Gene. 2023 Jul 6:147602. doi: 10.1016/j.gene.2023.147602. Online ahead of print.ABSTRACTThe color of a fruit is an important contributor to the perception of its nutritional value. It is widely acknowledged that the color of sweet cherry changes obviously during ripening. Variations in anthocyanins and flavonoids account for the heterogeneous color of sweet cherries. In this study, we showed that anthocyanins but not carotenoids determine the color of sweet cherry fruits. The difference between red-yellow and red sweet cherry may be attributed to seven anthocyanins, including Cyanidin-3-O-arabinoside, Cyanidin-3,5-O-diglucoside, Cyanidin 3-xyloside, Peonidin-3-O-glucoside, Peonidin-3-O-rutinoside, Cyanidin-3-O-galactoside, Cyanidin-3-O-glucoside (Kuromanin), Peonidin-3-O-rutinoside-5-O-glucoside, Pelargonidin-3-O-glucoside and Pelargonidin-3-O-rutinoside. The content of 85 flavonols differed between red and red-yellow sweet cherries. The transcriptional analysis identified 15 key structural genes involved in the flavonoid metabolic pathway and four R2R3-MYB transcription factors. The expression level of Pac4CL, PacPAL, PacCHS1, PacCHS2, PacCHI, PacF3H1, PacF3H2, PacF3'H, PacDFR, PacANS1, PacANS2, PacBZ1 and four R2R3-MYB were positively correlated with anthocyanin content (ps<0.05). PacFLS1, PacFLS2 and PacFLS3 expression was negatively correlated with anthocyanin content but positively correlated with flavonols content (ps<0.05). Overall, our findings suggests that the heterogeneous expression of structural genes in the flavonoid metabolic pathway accounts for the variation in levels of final metabolites, leading to differences between red 'Red-Light' and red-yellow 'Bright Pearl'.PMID:37422177 | DOI:10.1016/j.gene.2023.147602

Hepatic and ovarian effects of perfluorooctanoic acid exposure differ in lean and obese adult female mice

Sat, 08/07/2023 - 12:00
Toxicol Appl Pharmacol. 2023 Jul 6:116614. doi: 10.1016/j.taap.2023.116614. Online ahead of print.ABSTRACTObesity and overweight cause poor oocyte quality, miscarriage, infertility, polycystic ovarian syndrome, and offspring birth defects and affects 40% and 20% of US women and girls, respectively. Perfluorooctanoic acid (PFOA), a per- and poly-fluoroalkyl substance (PFAS), is environmentally persistent and has negative female reproductive effects including endocrine disruption, oxidative stress, altered menstrual cyclicity, and decreased fertility in humans and animal models. PFAS exposure is associated with non-alcoholic fatty liver disease which affects ~24-26% of the US population. This study investigated the hypothesis that PFOA exposure impacts hepatic and ovarian chemical biotransformation and alters the serum metabolome. At 7 weeks of age, female lean, wild type (KK.Cg-a/a) or obese (KK.Cg-Ay/J) mice received saline (C) or PFOA (2.5 mg/Kg) per os for 15 d. Hepatic weight was increased by PFOA exposure in both lean and obese mice (P < 0.05) and obesity also increased liver weight (P < 0.05) compared to lean mice. The serum metabolome was also altered (P < 0.05) by PFOA exposure and differed between lean and obese mice. Exposure to PFOA altered (P < 0.05) the abundance of ovarian proteins with roles in xenobiotic biotransformation (lean - 6; obese - 17), metabolism of fatty acids (lean - 3; obese - 9), cholesterol (lean - 8; obese - 11), amino acids (lean - 18; obese - 19), glucose (lean - 7; obese - 10), apoptosis (lean - 18; obese - 13), and oxidative stress (lean - 3; obese - 2). Use of qRT-PCR determined that exposure to PFOA increased (P < 0.05) hepatic Ces1 and Chst1 in lean but Ephx1 and Gstm3 in obese mice. Also, obesity basally increased (P < 0.05) Nat2, Gpi and Hsd17b2 mRNA levels. These data identify molecular changes resultant from PFOA exposure that may cause liver injury and ovotoxicity in females. In addition, differences in toxicity induced by PFOA exposure occurs in lean and obese mice.PMID:37422089 | DOI:10.1016/j.taap.2023.116614

Microbiota dysbiosis associated with type 2 diabetes-like effects caused by chronic exposure to a mixture of chlorinated persistent organic pollutants in zebrafish

Sat, 08/07/2023 - 12:00
Environ Pollut. 2023 Jul 6:122108. doi: 10.1016/j.envpol.2023.122108. Online ahead of print.ABSTRACTMixtures of chlorinated persistent organic pollutants (C-POPs-Mix) are chemically related risk factors for type 2 diabetes mellitus (T2DM); however, the effects of chronic exposure to C-POPs-Mix on microbial dysbiosis remain poorly understood. Herein, male and female zebrafish were exposed to C-POPs-Mix at a 1:1 ratio of five organochlorine pesticides and Aroclor 1254 at concentrations of 0.02, 0.1, and 0.5 μg/L for 12 weeks. We measured T2DM indicators in blood and profiled microbial abundance and richness in the gut as well as transcriptomic and metabolomic alterations in the liver. Exposure to C-POPs-Mix significantly increased blood glucose levels while decreasing the abundance and alpha diversity of microbial communities only in females at concentrations of 0.02 and 0.1 μg/L. The majorly identified microbial contributors to microbial dysbiosis were Bosea minatitlanensis, Rhizobium tibeticum, Bifidobacterium catenulatum, Bifidobacterium adolescentis, and Collinsella aerofaciens. PICRUSt results suggested that altered pathways were associated with glucose and lipid production and inflammation, which are linked to changes in the transcriptome and metabolome of the zebrafish liver. Metagenomics outcomes revealed close relationships between intestinal and liver disruptions to T2DM-related molecular pathways. Thus, microbial dysbiosis in T2DM-triggered zebrafish occurred as a result of chronic exposure to C-POPs-Mix, indicating strong host-microbiome interactions.PMID:37422083 | DOI:10.1016/j.envpol.2023.122108

Plasma lipids are dysregulated preceding diagnosis of preeclampsia or delivery of a growth restricted infant

Sat, 08/07/2023 - 12:00
EBioMedicine. 2023 Jul 6;94:104704. doi: 10.1016/j.ebiom.2023.104704. Online ahead of print.ABSTRACTBACKGROUND: Lipids serve as multifunctional metabolites that have important implications for the pregnant mother and developing fetus. Abnormalities in lipids have emerged as potential risk factors for pregnancy diseases, such as preeclampsia and fetal growth restriction. The aim of this study was to assess the potential of lipid metabolites for detection of late-onset preeclampsia and fetal growth restriction.METHODS: We used a case-cohort of 144 maternal plasma samples at 36 weeks' gestation from patients before the diagnosis of late-onset preeclampsia (n = 22), delivery of a fetal growth restricted infant (n = 55, defined as <5th birthweight centile), gestation-matched controls (n = 72). We performed liquid chromatography-tandem mass spectrometry (LC-QQQ) -based targeted lipidomics to identify 421 lipids, and fitted logistic regression models for each lipid, correcting for maternal age, BMI, smoking, and gestational diabetes.FINDINGS: Phosphatidylinositol 32:1 (AUC = 0.81) and cholesterol ester 17:1 (AUC = 0.71) best predicted the risk of developing preeclampsia or delivering a fetal growth restricted infant, respectively. Five times repeated five-fold cross validation demonstrated the lipids alone did not out-perform existing protein biomarkers, soluble tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) for the prediction of preeclampsia or fetal growth restriction. However, lipids combined with sFlt-1 and PlGF measurements improved disease prediction.INTERPRETATION: This study successfully identified 421 lipids in maternal plasma collected at 36 weeks' gestation from participants who later developed preeclampsia or delivered a fetal growth restricted infant. Our results suggest the predictive capacity of lipid measurements for gestational disorders holds the potential to improve non-invasive assessment of maternal and fetal health.FUNDING: This study was funded by a grant from National Health and Medical Research Council.PMID:37421807 | DOI:10.1016/j.ebiom.2023.104704

Exploring the effects of the fermentation method on the quality of Lycium barbarum and Polygonatum cyrtonema compound wine based on LC-MS metabolomics

Sat, 08/07/2023 - 12:00
Food Chem. 2023 Jul 5;428:136770. doi: 10.1016/j.foodchem.2023.136770. Online ahead of print.ABSTRACTThis study aimed to examine the effect of fermentation methods on the quality of Lycium barbarum and Polygonatum cyrtonema compound wine (LPW) by combining non-targeted metabolomic approaches with chemometrics and path profiling to determine the chemical and metabolic properties of LPW. The results demonstrated that SRA had higher leaching rates of total phenols and flavonoids, reaching 4.20 ± 0.10 v/v ethanol concentration. According to LC-MS non-targeting genomics, the metabolic profiles of LPW prepared by different mixtures of fermentation methods (Saccharomyces cerevisiae RW; Debaryomyces hansenii AS2.45) of yeast differed significantly. Amino acids, phenylpropanoids, flavonols, etc., were identified as the differential metabolites between different comparison groups. The pathways of tyrosine metabolism, biosynthesis of phenylpropanoids, and metabolism of 2-oxocarboxylic acids enriched 17 distinct metabolites. SRA stimulated the production of tyrosine and imparted a distinctive saucy aroma to the wine samples, providing a novel research concept for the microbial fermentation-based production of tyrosine.PMID:37421664 | DOI:10.1016/j.foodchem.2023.136770

Exopolysaccharide-Producing <em>Lacticaseibacillus rhamnosus</em> Space Mutant Improves the Techno-Functional Characteristics of Fermented Cow and Goat Milks

Sat, 08/07/2023 - 12:00
J Agric Food Chem. 2023 Jul 8. doi: 10.1021/acs.jafc.3c02381. Online ahead of print.ABSTRACTLacticaseibacillus rhamnosus Probio-M9 (Probio-M9) is increasingly used as a co-fermentation culture in fermented milk production. Recently, a capsular polysaccharide (CPS)- and exopolysaccharide (EPS)-producing mutant of Probio-M9, HG-R7970-3, was generated by space mutagenesis. This study compared the performance of cow and goat milk fermentation between the non-CPS/-EPS-producing parental strain (Probio-M9) and the CPS/EPS producer (HG-R7970-3), and the stability of products fermented by the two bacteria. Our results showed that using HG-R7970-3 as the fermentative culture could improve the probiotic viable counts, physico-chemical, texture, and rheological properties in both cow and goat milk fermentation. Substantial differences were also observed in the metabolomics profiles between fermented cow and goat milks produced by the two bacteria. Comparing with Probio-M9-fermented cow and goat milks, those fermented by HG-R7970-3 were enriched in a number of flavor compounds and potential functional components, particularly acids, esters, peptides, and intermediate metabolites. Moreover, HG-R7970-3 could improve the post-fermentation flavor retention capacity. These new and added features are of potential to improve the techno-functional qualities of conventional fermented milks produced by Probio-M9, and these differences are likely imparted by the acquired CPS-/EPS-producing ability of the mutant. It merits further investigation into the sensory quality and in vivo function of HG-R7970-3-fermented milks.PMID:37421368 | DOI:10.1021/acs.jafc.3c02381

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