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

Integrated analysis of gut metabolome, microbiome, and brain function reveal the role of gut-brain axis in longevity

Thu, 28/03/2024 - 11:00
Gut Microbes. 2024 Jan-Dec;16(1):2331434. doi: 10.1080/19490976.2024.2331434. Epub 2024 Mar 28.ABSTRACTThe role of microbiota-gut-brain axis in modulating longevity remains undetermined. Here, we performed a multiomics analysis of gut metagenomics, gut metabolomics, and brain functional near-infrared spectroscopy (fNIRS) in a cohort of 164 participants, including 83 nonagenarians (NAs) and 81 non-nonagenarians (NNAs) matched with their spouses and offspring. We found that 438 metabolites were significantly different between the two groups; among them, neuroactive compounds and anti-inflammatory substances were enriched in NAs. In addition, increased levels of neuroactive metabolites in NAs were significantly associated with NA-enriched species that had three corresponding biosynthetic potentials: Enterocloster asparagiformis, Hungatella hathewayi and Oxalobacter formigenes. Further analysis showed that the altered gut microbes and metabolites were linked to the enhanced brain connectivity in NAs, including the left dorsolateral prefrontal cortex (DLPFC)-left premotor cortex (PMC), left DLPFC-right primary motor area (M1), and right inferior frontal gyrus (IFG)-right M1. Finally, we found that neuroactive metabolites, altered microbe and enhanced brain connectivity contributed to the cognitive preservation in NAs. Our findings provide a comprehensive understanding of the microbiota-gut-brain axis in a long-lived population and insights into the establishment of a microbiome and metabolite homeostasis that can benefit human longevity and cognition by enhancing functional brain connectivity.PMID:38548676 | DOI:10.1080/19490976.2024.2331434

Divergent Gut Microbiota: Archaeal and Bacterial Signatures Unveil Unique Patterns in Colombian Cyclists Compared to Weightlifters and Non-Athletes

Thu, 28/03/2024 - 11:00
Adv Biol (Weinh). 2024 Mar 28:e2400069. doi: 10.1002/adbi.202400069. Online ahead of print.ABSTRACTEngagement in physical activity, across various sports, promotes a diverse microbiota in active individuals. This study examines the gut microbiota of Colombian athletes, specifically weightlifters (n = 16) and road cyclists (n = 13), compared to non-athletes (n = 15). Using Kruskal-Wallis tests, the physical activity level of a group of non-athletic individuals and the sports experience of a group of professional athletes is analyzed. The median age of participants is 24 years, comprising 25 men and 19 women. The microbiota is collected using fecal samples. Participants provided these samples during their pre-competitive stage, specifically during the concentration phase occurring two weeks prior to national competitions. This timing is chosen to capture the microbial composition during a period of heightened physical preparation. Questionnaire responses and microbial composition assessments identify disparities among groups. Microbial composition analysis explores core microbiome, abundance, and taxonomy using Pavian, MicrobiomeAnalyst 2.0, and GraPhlAn. ANCOM-BC2 reveals differentially abundant species. Road cyclists exhibit decreased Bacteria and increased Archaea abundance. Phylum-level variations included Planctomycetes, Acidobacteria, and Proteobacteria, while Bacteroidetes prevailed. Key families influencing gut microbiota are Bacteroidaceae, Muribaculaceae, and Selenomonadaceae. Weightlifters exhibit unique viral and archaeal community connections, while cyclists showed specialized microbial interplay influenced by endurance exercise. Correlation network analysis emphasizes distinctive microbial interactions within athlete groups, shedding light on the impact of physical activities on gut microbiota and athlete health.PMID:38548661 | DOI:10.1002/adbi.202400069

Evaluation of metabolomics-based urinary biomarker models for recognizing major depression disorder and bipolar disorder

Thu, 28/03/2024 - 11:00
J Affect Disord. 2024 Mar 26:S0165-0327(24)00537-8. doi: 10.1016/j.jad.2024.03.114. Online ahead of print.ABSTRACTBACKGROUND: Major depressive disorder (MDD) and bipolar disorder (BD) are psychiatric disorders with overlapping symptoms, leading to high rates of misdiagnosis due to the lack of biomarkers for differentiation. This study aimed to identify metabolic biomarkers in urine samples for diagnosing MDD and BD, as well as to establish unbiased differential diagnostic models.METHODS: We utilized a metabolomics approach employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) to analyze the metabolic profiles of urine samples from individuals with MDD (n = 50), BD (n = 12), and healthy controls (n = 50). The identification of urine metabolites was verified using MS data analysis tools and online metabolite databases.RESULTS: Two diagnostic panels consisting of a combination of metabolites and clinical indicators were identified-one for MDD and another for BD. The discriminative capacity of these panels was assessed using the area under the receiver operating characteristic (ROC) curve, yielding an Area Under the Curve (AUC) of 0.9084 for MDD and an AUC value of 0.9017 for BD.CONCLUSIONS: High-resolution mass spectrometry-based assays show promise in identifying urinary biomarkers for depressive disorders. The combination of urine metabolites and clinical indicators is effective in differentiating healthy controls from individuals with MDD and BD. The metabolic pathway indicating oxidative stress is seen to significantly contribute to depressive disorders.PMID:38548210 | DOI:10.1016/j.jad.2024.03.114

Metabolomic Profiles during Early Childhood and Risk of Food Allergies and Asthma in Multi-ethnic Children from a Prospective Birth Cohort

Thu, 28/03/2024 - 11:00
J Allergy Clin Immunol. 2024 Mar 26:S0091-6749(24)00295-1. doi: 10.1016/j.jaci.2024.02.024. Online ahead of print.ABSTRACTBACKGROUND: There are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations.OBJECTIVE: To identify metabolites which are unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort (the Boston Birth Cohort).METHODS: Mass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (N=811). FA was diagnosed based on clinical symptoms consistent with an acute hypersensitivity reaction upon food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined based on physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders.RESULTS: During a median follow-up of 11.8±5.2 years from birth, 78 children developed FA and 171 developed asthma. Androgenic and pregnenolone steroids were significantly associated with a lower risk of FA, especially for egg allergy. N,N,N-trimethyl-5-aminovalerate (OR=0.65, 95%CI=0.48-0.87) and 1-Oleoyl-2-arachidonoyl-sn-glycero-3-phosphoinositol (OR=0.77, 95%CI=0.66-0.90) were inversely associated with FA risk. Orotidine (OR=4.73, 95%CI=2.2-10.2) and 4-cholesten-3-one (OR=0.52, 95%CI=0.35-0.77) were the top two metabolites associated with risk of asthma, although they had no association with FA. In comparison, children with both FA and asthma exhibited an altered metabolomic profile that aligned with that of FA, including altered levels of lipids and steroids.CONCLUSION: In this U.S. multi-ethnic prospective birth cohort, unique and shared alterations in plasma metabolites during early childhood were associated with risk of developing FA, asthma, or both. These findings await further validation.PMID:38548091 | DOI:10.1016/j.jaci.2024.02.024

Urban and agricultural influences on the coastal dissolved organic matter pool in the Algoa Bay estuaries

Thu, 28/03/2024 - 11:00
Chemosphere. 2024 Mar 26:141782. doi: 10.1016/j.chemosphere.2024.141782. Online ahead of print.ABSTRACTWhile anthropogenic pollution is a major threat to aquatic ecosystem health, our knowledge of the presence of xenobiotics in coastal Dissolved Organic Matter (DOM) is still relatively poor. This is especially true for water bodies in the Global South with limited information gained mostly from targeted studies that rely on comparison with authentic standards. In recent years, non-targeted tandem mass spectrometry has emerged as a powerful tool to collectively detect and identify pollutants and biogenic DOM components in the environment, but this approach has yet to be widely utilized for monitoring ecologically important aquatic systems. In this study we compared the DOM composition of Algoa Bay, Eastern Cape, South Africa, and its two estuaries. The Swartkops Estuary is highly urbanized and severely impacted by anthropogenic pollution, while the Sundays Estuary is impacted by commercial agriculture in its catchment. We employed solid-phase extraction followed by liquid chromatography tandem mass spectrometry to annotate more than 200 pharmaceuticals, pesticides, urban xenobiotics, and natural products based on spectral matching. The identification with authentic standards confirmed the presence of methamphetamine, carbamazepine, sulfamethoxazole, N-acetylsulfamethoxazole, imazapyr, caffeine and hexa(methoxymethyl)melamine, and allowed semi-quantitative estimations for annotated xenobiotics. The Swartkops Estuary DOM composition was strongly impacted by features annotated as urban pollutants including pharmaceuticals such as melamines and antiretrovirals. By contrast, the Sundays Estuary exhibited significant enrichment of molecules annotated as agrochemicals widely used in the citrus farming industry, with predicted concentrations for some of them exceeding predicted no-effect concentrations. This study provides new insight into anthropogenic impact on the Algoa Bay system and demonstrates the utility of non-targeted tandem mass spectrometry as a sensitive tool for assessing the health of ecologically important coastal ecosystems and will serve as a valuable foundation for strategizing long-term monitoring efforts.PMID:38548083 | DOI:10.1016/j.chemosphere.2024.141782

Systematic optimization of automated phosphopeptide enrichment for high-sensitivity phosphoproteomics

Thu, 28/03/2024 - 11:00
Mol Cell Proteomics. 2024 Mar 26:100754. doi: 10.1016/j.mcpro.2024.100754. Online ahead of print.ABSTRACTImproving coverage, robustness and sensitivity is crucial for routine phosphoproteomics analysis by single-shot liquid chromatography tandem mass spectrometry (LC-MS/MS) from minimal peptide inputs. Here, we systematically optimized key experimental parameters for automated on-beads phosphoproteomics sample preparation with focus on low input samples. Assessing the number of identified phosphopeptides, enrichment efficiency, site localization scores and relative enrichment of multiply-phosphorylated peptides pinpointed critical variables influencing the resulting phosphoproteome. Optimizing glycolic acid concentration in the loading buffer, percentage of ammonium hydroxide in the elution buffer, peptide-to-beads ratio, binding time, sample and loading buffer volumes, allowed us to confidently identify >16,000 phosphopeptides in half-an-hour LC-MS/MS on an Orbitrap Exploris 480 using 30 μg of peptides as starting material. Furthermore, we evaluated how sequential enrichment can boost phosphoproteome coverage and showed that pooling fractions into a single LC-MS/MS analysis increased the depth. We also present an alternative phosphopeptide enrichment strategy based on stepwise addition of beads thereby boosting phosphoproteome coverage by 20%. Finally, we applied our optimized strategy to evaluate phosphoproteome depth with the Orbitrap Astral MS using a cell dilution series and were able to identify >32,000 phosphopeptides from 0.5 million HeLa cells in half-an-hour LC-MS/MS using narrow-window data-independent acquisition (nDIA).PMID:38548019 | DOI:10.1016/j.mcpro.2024.100754

Combined exposure to decabromodiphenyl ether and nano zero-valent iron aggravated oxidative stress and interfered with metabolism in earthworms

Thu, 28/03/2024 - 11:00
Sci Total Environ. 2024 Mar 26:172033. doi: 10.1016/j.scitotenv.2024.172033. Online ahead of print.ABSTRACTDecabromodiphenyl ether (BDE-209) is a common brominated flame retardant in electronic waste, and nano zero-valent iron (nZVI) is a new material in the field of environmental remediation. Little is known about how BDE-209 and nZVI combined exposure influences soil organisms. During the 28 days study, we determined the effects of single and combined exposures to BDE-209 and nZVI on the oxidative stress and metabolic response of earthworms (Eisenia fetida). On day 7, compared to CK, malondialdehyde (MDA) content increased in most combined exposure groups. To remove MDA and reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities were induced in most combined exposure groups. On day 28, compared to CK, the activities of SOD and CAT were inhibited, while POD activity was significantly induced, indicating that POD plays an important role in scavenging ROS. Combined exposure to BDE-209 and nZVI significantly affected amino acid biosynthesis and metabolism, purine metabolism, and aminoacyl-tRNA biosynthesis pathways, interfered with energy metabolism, and aggravated oxidative stress in earthworms. These findings provide a basis for assessing the ecological impacts of using nZVI to remediate soils contaminated with BDE-209 from electronic waste.PMID:38547968 | DOI:10.1016/j.scitotenv.2024.172033

Transketolase promotes MAFLD by limiting inosine-induced mitochondrial activity

Thu, 28/03/2024 - 11:00
Cell Metab. 2024 Mar 23:S1550-4131(24)00082-2. doi: 10.1016/j.cmet.2024.03.003. Online ahead of print.ABSTRACTMetabolic dysfunction-associated fatty liver disease (MAFLD) has a global prevalence of about 25% and no approved therapy. Using metabolomic and proteomic analyses, we identified high expression of hepatic transketolase (TKT), a metabolic enzyme of the pentose phosphate pathway, in human and mouse MAFLD. Hyperinsulinemia promoted TKT expression through the insulin receptor-CCAAT/enhancer-binding protein alpha axis. Utilizing liver-specific TKT overexpression and knockout mouse models, we demonstrated that TKT was sufficient and required for MAFLD progression. Further metabolic flux analysis revealed that Tkt deletion increased hepatic inosine levels to activate the protein kinase A-cAMP response element binding protein cascade, promote phosphatidylcholine synthesis, and improve mitochondrial function. Moreover, insulin induced hepatic TKT to limit inosine-dependent mitochondrial activity. Importantly, N-acetylgalactosamine (GalNAc)-siRNA conjugates targeting hepatic TKT showed promising therapeutic effects on mouse MAFLD. Our study uncovers how hyperinsulinemia regulates TKT-orchestrated inosine metabolism and mitochondrial function and provides a novel therapeutic strategy for MAFLD prevention and treatment.PMID:38547864 | DOI:10.1016/j.cmet.2024.03.003

Meta-metabolomic responses of river biofilms to cobalt exposure and use of dose-response model trends as an indicator of effects

Thu, 28/03/2024 - 11:00
J Hazard Mater. 2024 Mar 20;470:134099. doi: 10.1016/j.jhazmat.2024.134099. Online ahead of print.ABSTRACTThe response of the meta-metabolome is rarely used to characterize the effects of contaminants on a whole community. Here, the meta-metabolomic fingerprints of biofilms were examined after 1, 3 and 7 days of exposure to five concentrations of cobalt (from background concentration to 1 × 10-5 M) in aquatic microcosms. The untargeted metabolomic data were processed using the DRomics tool to build dose-response models and to calculate benchmark-doses. This approach made it possible to use 100% of the chemical signal instead of being limited to the very few annotated metabolites (7%). These benchmark-doses were further aggregated into an empirical cumulative density function. A trend analysis of the untargeted meta-metabolomic feature dose-response curves after 7 days of exposure suggested the presence of a concentration range inducing defense responses between 1.7 × 10-9 and 2.7 × 10-6 M, and of a concentration range inducing damage responses from 2.7 × 10-6 M and above. This distinction was in good agreement with changes in the other biological parameters studied (biomass and chlorophyll content). This study demonstrated that the molecular defense and damage responses can be related to contaminant concentrations and represents a promising approach for environmental risk assessment of metals.PMID:38547754 | DOI:10.1016/j.jhazmat.2024.134099

Discrimination and prediction of Qingzhuan tea storage year using quantitative chemical profile combined with multivariate analysis: Advantages of MRM(HR) based targeted quantification metabolomics

Thu, 28/03/2024 - 11:00
Food Chem. 2024 Mar 21;448:139088. doi: 10.1016/j.foodchem.2024.139088. Online ahead of print.ABSTRACTThe duration of storage significantly influences the quality and market value of Qingzhuan tea (QZT). Herein, a high-resolution multiple reaction monitoring (MRMHR) quantitative method for markers of QZT storage year was developed. Quantitative data alongside multivariate analysis were employed to discriminate and predict the storage year of QZT. Furthermore, the content of the main biochemical ingredients, catechins and alkaloids, and free amino acids (FAA) were assessed for this purpose. The results show that targeted marker-based models exhibited superior discrimination and prediction performance among four datasets. The R2Xcum, R2Ycum and Q2cum of orthogonal projection to latent structure-discriminant analysis discrimination model were close to 1. The correlation coefficient (R2) and the root mean square error of prediction of the QZT storage year prediction model were 0.9906 and 0.63, respectively. This study provides valuable insights into tea storage quality and highlights the potential application of targeted markers in food quality evaluation.PMID:38547707 | DOI:10.1016/j.foodchem.2024.139088

Analysis of alterations in serum vitamins and correlations with gut microbiome, microbial metabolomics in patients with sepsis

Thu, 28/03/2024 - 11:00
J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Mar 26;1237:124101. doi: 10.1016/j.jchromb.2024.124101. Online ahead of print.ABSTRACTBACKGROUND: Vitamins are essential micronutrients that play key roles in many biological pathways associated with sepsis. The gut microbiome plays a pivotal role in the progression of sepsis and may contribute to the onset of multi-organ dysfunction syndrome (MODS). The aim of this study was to investigate the changes in serum vitamins, and their correlation with intestinal flora and metabolomic profiles in patients with sepsis.METHODS: The serum levels of vitamins were determined by Ultra Performance Liquid Chromatography (UPLC). 16S rRNA gene sequencing and Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) targeted metabolomics were used for microbiome and metabolome analysis.RESULTS: In the training cohort: After univariate, multivariate (OPLS-DA) and Spearman analyses, it was concluded that vitamin levels of 25 (OH) VD3 and (VD2 + VD3), as well as vitamins A and B9, differed significantly among healthy controls (HC), non-septic critical patients (NS), and sepsis patients (SS) (P < 0.05). The validation cohort confirmed the differential vitamin findings from the training cohort. Moreover, analyses of gut flora and metabolites in septic patients and healthy individuals revealed differential flora, metabolites, and metabolic pathways that were linked to alterations in serum vitamin levels. We found for the first time that vitamin B9 was negatively correlated with g_Sellimonas.CONCLUSION: Sepsis patients exhibited significantly lower levels of 25 (OH) VD3 and (VD2 + VD3), vitamins A and B9, which hold potential as predictive markers for sepsis prognosis. The changes in these vitamins may be associated with inflammatory factors, oxidative stress, and changes in gut flora.PMID:38547698 | DOI:10.1016/j.jchromb.2024.124101

Xiebai San alleviates acute lung injury by inhibiting the phosphorylation of the ERK/Stat3 pathway and regulating multiple metabolisms

Thu, 28/03/2024 - 11:00
Phytomedicine. 2024 Jan 26;128:155397. doi: 10.1016/j.phymed.2024.155397. Online ahead of print.ABSTRACTBACKGROUND: Acute lung injury (ALI) often leads to serious respiratory diseases with high incidence rates and mortality. For centuries, Xiebai San (XBS) has been a classical traditional Chinese medicine (TCM) about respiratory illness such as pneumonia in children. However, the related mechanism of XBS against ALI remains indistinct.PURPOSE: To reveal specific targets of XBS in lipopolysaccharide (LPS)-induced ALI mice using integrated pharmacology.STUDY DESIGN: The integrated method was to expound mechanism and targets of XBS inhibited ALI.METHODS: The primary components in XBS were identified by ultra high performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS). The potential drug targets were established using network pharmacology. The anti-ALI effect of XBS was evaluated in mice. Additionally, therapeutic targets were screened by integrating metabolome and transcriptome and verified in lung tissue.RESULTS: In total, 163 chemical components were identified in XBS, and a network of "3 drugs-18 components-86 targets" for XBS against ALI was constructed. In ALI mice, XBS alleviated lung inflammation by decreasing permeation and expression of neutrophils, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF), serum, and lung tissue. Next, the transcriptome of lung tissue was analyzed and enriched, indicating the importance of mitogen-activated protein kinase (MAPK), Janus kinase-signal transducer and activator of transcription (JAK-STAT), and others, which was consistent with network pharmacology prediction. Also, western blotting and immunohistochemistry results showed that XBS was against ALI mainly by inhibiting extracellular signal regulated kinase (ERK) and signal transducer and activator of transcription 3 (Stat3) phosphorylation. In addition, the metabolome of lung tissue revealed that XBS mainly regulated pathways involved in arachidonic acid, glycerophospholipid, and tryptophan metabolisms. The expression levels of leukotriene, phosphatidylcholine, kynurenine, and others were also verified.CONCLUSION: XBS alleviated inflammation of ALI by inhibiting the phosphorylation of the ERK/Stat3 pathway and regulating arachidonic acid, glycerophospholipid, and tryptophan metabolisms. This study will guide clinical precision medicine and promote modernization of XBS.PMID:38547623 | DOI:10.1016/j.phymed.2024.155397

Enhancing β-cell function and identity in type 2 diabetes: The protective role of Coptis deltoidea C. Y. Cheng et Hsiao via glucose metabolism modulation and AMPK signaling activation

Thu, 28/03/2024 - 11:00
Phytomedicine. 2024 Jan 28;128:155396. doi: 10.1016/j.phymed.2024.155396. Online ahead of print.ABSTRACTBACKGROUND: Abnormalities in glucose metabolism may be the underlying cause of β-cell dysfunction and identity impairment resulting from high glucose exposure. In China, Coptis deltoidea C. Y. Cheng et Hsiao (YL) has demonstrated remarkable hypoglycemic effects.HYPOTHESIS/PURPOSE: To investigate the hypoglycemic effect of YL and determine the mechanism of YL in treating diabetes.METHODS: A type 2 diabetes mouse model was used to investigate the pharmacodynamics of YL. YL was administrated once daily for 8 weeks. The hypoglycemic effect of YL was assessed by fasting blood glucose, an oral glucose tolerance test, insulin levels, and other indexes. The underlying mechanism of YL was examined by targeting glucose metabolomics, western blotting, and qRT-PCR. Subsequently, the binding capacity between predicted AMP-activated protein kinase (AMPK) and important components of YL (Cop, Ber, and Epi) were validated by molecular docking and surface plasmon resonance. Then, in AMPK knockdown MIN6 cells, the mechanisms of Cop, Ber, and Epi were inversely confirmed through evaluations encompassing glucose-stimulated insulin secretion, markers indicative of β-cell identity, and the examination of glycolytic genes and products.RESULTS: YL (0.9 g/kg) treatment exerted notable hypoglycemic effects and protected the structural integrity and identity of pancreatic β-cells. Metabolomic analysis revealed that YL inhibited the hyperactivated glycolysis pathway in diabetic mice, thereby regulating the products of the tricarboxylic acid cycle. KEGG enrichment revealed the intimate relationship of this process with the AMPK signaling pathway. Cop, Ber, and Epi in YL displayed high binding affinities for AMPK protein. These compounds played a pivotal role in preserving the identity of pancreatic β-cells and amplifying insulin secretion. The mechanism underlying this process involved inhibition of glucose uptake, lowering intracellular lactate levels, and elevating acetyl coenzyme A and ATP levels through AMPK signaling. The use of a glycolytic inhibitor corroborated that attenuation of glycolysis restored β-cell identity and function.CONCLUSION: YL demonstrates significant hypoglycemic efficacy. We elucidated the potential mechanisms underlying the protective effects of YL and its active constituents on β-cell function and identity by observing glucose metabolism processes in pancreatic tissue and cells. In this intricate process, AMPK plays a pivotal regulatory role.PMID:38547617 | DOI:10.1016/j.phymed.2024.155396

Can digital twin efforts shape microorganism-based alternative food?

Thu, 28/03/2024 - 11:00
Curr Opin Biotechnol. 2024 Mar 27;87:103115. doi: 10.1016/j.copbio.2024.103115. Online ahead of print.ABSTRACTWith the continuous increment in global population growth, compounded by post-pandemic food security challenges due to labor shortages, effects of climate change, political conflicts, limited land for agriculture, and carbon emissions control, addressing food production in a sustainable manner for future generations is critical. Microorganisms are potential alternative food sources that can help close the gap in food production. For the development of more efficient and yield-enhancing products, it is necessary to have a better understanding on the underlying regulatory molecular pathways of microbial growth. Nevertheless, as microbes are regulated at multiomics scales, current research focusing on single omics (genomics, proteomics, or metabolomics) independently is inadequate for optimizing growth and product output. Here, we discuss digital twin (DT) approaches that integrate systems biology and artificial intelligence in analyzing multiomics datasets to yield a microbial replica model for in silico testing before production. DT models can thus provide a holistic understanding of microbial growth, metabolite biosynthesis mechanisms, as well as identifying crucial production bottlenecks. Our argument, therefore, is to support the development of novel DT models that can potentially revolutionize microorganism-based alternative food production efficiency.PMID:38547588 | DOI:10.1016/j.copbio.2024.103115

Optimization of volatile organic compounds sampling from dairy cow exhaled breath using polymer-based solid-phase extraction cartridges for gas chromatographic analysis

Thu, 28/03/2024 - 11:00
J Breath Res. 2024 Mar 28. doi: 10.1088/1752-7163/ad38d5. Online ahead of print.ABSTRACTWe explored appropriate technical setups for the detection of volatile organic compounds (VOCs) from exhaled cow breath by comparing six different polymer-based solid-phase extraction (SPE) cartridges currently on the market for GC-MS screening. Exhaled breath was sampled at a single timepoint from five lactating dairy cows using six different SPE cartridges (Bond Elut ENV; Chromabond HRX; Chromabond HRP; Chromabond HLB; Chromabond HR-XCW and Chromabond HR-XAW). The trapped VOCs were analyzed by Dynamic Headspace Vacuum In-Tube Extraction gas chromatography/mass spectrometry (DHS-V-ITEX-GC-MS). Depending on the SPE cartridge, we detected 1174 to 1312 VOCs per cartridge. Most VOCs were alkenes, alkanes, esters, ketones, alcohols, aldehydes, amines, nitriles, ethers, amides, carboxylic acids, alkynes, azoles, terpenes, pyridines, or sulfur-containing compounds. The six SPE cartridges differed in their specificity for the chemical compounds, with the XAW cartridge showing the best specificity for ketones. The greatest differences between the tested SPE cartridges appeared in the detection of specific VOCs. In total, 176 different VOCs were detected with a match factor >80%. The greatest number of specific VOCs was captured by XAW (149), followed by ENV (118), HLB (117), HRP (115), HRX (114), and XCW (114)). We conclude that the tested SPE cartridges are suitable for VOC sampling from exhaled cow breath, but the SPE cartridge choice enormously affects the detected chemical groups and the number of detected VOCs. Therefore, an appropriate SPE adsorbent cartridge should be selected according to our proposed inclusion criteria. For targeted metabolomics approaches, the SPE cartridge choice depends on the VOCs or chemical compound groups of interest based on our provided VOC list. For untargeted approaches without information on the animals' metabolic condition, we suggest using multi-sorbent SPE cartridges or multiple cartridges per animal.PMID:38547532 | DOI:10.1088/1752-7163/ad38d5

Metabolomics of Multiple Sclerosis Lesions Demonstrates Lipid Changes Linked to Alterations in Transcriptomics-Based Cellular Profiles

Thu, 28/03/2024 - 11:00
Neurol Neuroimmunol Neuroinflamm. 2024 May;11(3):e200219. doi: 10.1212/NXI.0000000000200219. Epub 2024 Mar 28.ABSTRACTBACKGROUND AND OBJECTIVES: People with multiple sclerosis (MS) have a dysregulated circulating metabolome, but the metabolome of MS brain lesions has not been studied. The aims of this study were to identify differences in the brain tissue metabolome in MS compared with controls and to assess its association with the cellular profile of corresponding tissue.METHODS: MS tissues included samples from the edge and core of chronic active or inactive lesions and periplaque white matter (WM). Control specimens were obtained from normal WM. Metabolomic analysis was performed using mass-spectrometry coupled with liquid/gas chromatography and subsequently integrated with single-nucleus RNA-sequencing data by correlating metabolite abundances with relative cell counts, as well as individual genes using Multiomics Factor Analysis (MOFA).RESULTS: Seventeen samples from 5 people with secondary progressive MS and 8 samples from 6 controls underwent metabolomic profiling identifying 783 metabolites. MS lesions had higher levels of sphingosines (false discovery rate-adjusted p-value[q] = 2.88E-05) and sphingomyelins and ceramides (q = 2.15E-07), but lower nucleotide (q = 0.05), energy (q = 0.001), lysophospholipid (q = 1.86E-07), and monoacylglycerol (q = 0.04) metabolite levels compared with control WM. Periplaque WM had elevated sphingomyelins and ceramides (q = 0.05) and decreased energy metabolites (q = 0.01) and lysophospholipids (q = 0.05) compared with control WM. Sphingolipids and membrane lipid metabolites were positively correlated with astrocyte and immune cell abundances and negatively correlated with oligodendrocytes. On the other hand, long-chain fatty acid, endocannabinoid, and monoacylglycerol pathways were negatively correlated with astrocyte and immune cell populations and positively correlated with oligodendrocytes. MOFA demonstrated associations between differentially expressed metabolites and genes involved in myelination and lipid biosynthesis.DISCUSSION: MS lesions and perilesional WM demonstrated a significantly altered metabolome compared with control WM. Many of the altered metabolites were associated with altered cellular composition and gene expression, indicating an important role of lipid metabolism in chronic neuroinflammation in MS.PMID:38547430 | DOI:10.1212/NXI.0000000000200219

Chemical composition of the White Sea sponge <em>Halichondriа panicea</em>

Thu, 28/03/2024 - 11:00
Nat Prod Res. 2024 Mar 28:1-8. doi: 10.1080/14786419.2024.2333049. Online ahead of print.ABSTRACTThe extract of the White Sea sponge Halichondria panicea (Pallas, 1766) exhibits cytotoxic and cytostatic effects. The main part of the extract consists of hydrophilic low molecular weight compounds: free amino acids (13.9%), glucose (19.9%), polyatomic alcohols (glycerin and others) (6.1%), carboxylic acids (0.7%) and nitrogenous heterocycles (1.2%). Of the substances specific to the metabolome, bicyclic diketopiperazines (four derivatives), pyroglutamic acid, phenylacetic acid, and two steroids (3β,5α)cholest-7-en-3-ol and dihydrocholesterol were identified. Toxicants characteristic of the genus Halichondria were not found in the White Sea sponge.PMID:38547385 | DOI:10.1080/14786419.2024.2333049

Application of Metabolomics Across the Spectrum of Pulmonary and Critical Care Medicine

Thu, 28/03/2024 - 11:00
Am J Respir Cell Mol Biol. 2024 Mar 28. doi: 10.1165/rcmb.2024-0080PS. Online ahead of print.ABSTRACTIn recent years, metabolomics, the systematic study of small molecule metabolites in biological samples, has yielded fresh insights into the molecular determinants of pulmonary diseases and critical illness. The purpose of this article is to orient the reader to this emerging field by discussing the fundamental tenets underlying metabolomics research, the tools and techniques that serve as foundational methodologies, and the various statistical approaches to analysis of metabolomics datasets. We present several examples of metabolomics applied to pulmonary and critical care medicine in order to illustrate the potential of this avenue of research to deepen our understanding of pathophysiology. We conclude by reviewing recent advances in the field and future research directions that stand to further the goal of personalizing medicine in order to improve patient care.PMID:38547373 | DOI:10.1165/rcmb.2024-0080PS

One-Shot Single-Cell Proteome and Metabolome Analysis Strategy for the Same Single Cell

Thu, 28/03/2024 - 11:00
Anal Chem. 2024 Mar 28. doi: 10.1021/acs.analchem.3c05659. Online ahead of print.ABSTRACTCharacterizing the profiles of proteome and metabolome at the single-cell level is of great significance in single-cell multiomic studies. Herein, we proposed a novel strategy called one-shot single-cell proteome and metabolome analysis (scPMA) to acquire the proteome and metabolome information in a single-cell individual in one injection of LC-MS/MS analysis. Based on the scPMA strategy, a total workflow was developed to achieve the single-cell capture, nanoliter-scale sample pretreatment, one-shot LC injection and separation of the enzyme-digested peptides and metabolites, and dual-zone MS/MS detection for proteome and metabolome profiling. Benefiting from the scPMA strategy, we realized dual-omic analysis of single tumor cells, including A549, HeLa, and HepG2 cells with 816, 578, and 293 protein groups and 72, 91, and 148 metabolites quantified on average. A single-cell perspective experiment for investigating the doxorubicin-induced antitumor effects in both the proteome and metabolome aspects was also performed.PMID:38547315 | DOI:10.1021/acs.analchem.3c05659

Pyrimidines maintain mitochondrial pyruvate oxidation to support de novo lipogenesis

Thu, 28/03/2024 - 11:00
Science. 2024 Mar 29;383(6690):1484-1492. doi: 10.1126/science.adh2771. Epub 2024 Mar 28.ABSTRACTCellular purines, particularly adenosine 5'-triphosphate (ATP), fuel many metabolic reactions, but less is known about the direct effects of pyrimidines on cellular metabolism. We found that pyrimidines, but not purines, maintain pyruvate oxidation and the tricarboxylic citric acid (TCA) cycle by regulating pyruvate dehydrogenase (PDH) activity. PDH activity requires sufficient substrates and cofactors, including thiamine pyrophosphate (TPP). Depletion of cellular pyrimidines decreased TPP synthesis, a reaction carried out by TPP kinase 1 (TPK1), which reportedly uses ATP to phosphorylate thiamine (vitamin B1). We found that uridine 5'-triphosphate (UTP) acts as the preferred substrate for TPK1, enabling cellular TPP synthesis, PDH activity, TCA-cycle activity, lipogenesis, and adipocyte differentiation. Thus, UTP is required for vitamin B1 utilization to maintain pyruvate oxidation and lipogenesis.PMID:38547260 | DOI:10.1126/science.adh2771

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