PubMed

Proteomics. 2024 Dec 10:e202400271. doi: 10.1002/pmic.202400271. Online ahead of print.ABSTRACTAdvances in high-throughput omics technologies have enabled system-wide characterization of biological samples across multiple molecular levels, such as the genome, transcriptome, and proteome. However, as sample sizes rapidly increase in large-scale multi-omics studies, sample mix-ups have become a prevalent issue, compromising data integrity and leading to erroneous conclusions. The interconnected nature of multi-omics data presents an opportunity to identify and correct these errors. This review examines the potential sources of sample mix-ups and evaluates the methodologies and tools developed for detecting and correcting these errors, with an emphasis on approaches applicable to proteomics data. We categorize existing tools into three main groups: expression/protein quantitative trait loci-based, genotype concordance-based, and gene/protein expression correlation-based approaches. Notably, only a handful of tools currently utilize the proteogenomics approach for correcting sample mix-ups at the proteomics level. Integrating the strengths of current tools across diverse data types could enable the development of more versatile and comprehensive solutions. In conclusion, verifying sample identity is a critical first step to reduce bias and increase precision in subsequent analyses for large-scale multi-omics studies. By leveraging these tools for identifying and correcting sample mix-ups, researchers can significantly improve the reliability and reproducibility of biomedical research.PMID:39659081 | DOI:10.1002/pmic.202400271

J Agric Food Chem. 2024 Dec 10. doi: 10.1021/acs.jafc.4c06072. Online ahead of print.ABSTRACTIn this study, we investigated the ameliorative effects of selenium-enriched Lactobacillus fermentum FZU3103 (Lf@Se) and its pathway on alcoholic liver injury (ALI) in mice. The results showed that Lf@Se was superior to Lf and inorganic selenium in alleviating ALI. Oral Lf@Se effectively prevented lipid metabolism disorders, improved liver function, promoted alcohol metabolism, and alleviated liver oxidative damage in mice. 16S amplicons sequencing indicated that Lf@Se intervention modulated intestinal flora homeostasis by increasing (decreasing) the abundance of beneficial bacteria (harmful bacteria), which is associated with the improvement of liver function. Besides, Lf@Se intervention altered the liver metabolic profile, and the characteristic biomarkers were mainly involved in tyrosine metabolism, retinol metabolism, galactose metabolism, and primary bile acid biosynthesis. Additionally, Lf@Se intervention regulated liver gene expression for lipid metabolism and oxidative stress. Western blot analysis revealed increased expression levels of intestinal tight junction proteins after Lf@Se intervention, thereby ameliorating alcohol-induced intestinal barrier damage.PMID:39658842 | DOI:10.1021/acs.jafc.4c06072

Adv Sci (Weinh). 2024 Dec 10:e2412222. doi: 10.1002/advs.202412222. Online ahead of print.ABSTRACTMammalian pre-implantation development is a complex process involving sophisticated regulatory dynamics. WD repeat domain 36 (WDR36) is known to play a critical role in mouse early embryonic development, but its regulatory function in human embryogenesis is still elusive due to limited access to human embryos. The human pluripotent stem cell-derived blastocyst-like structure, termed a blastoid, offers an alternative means to study human development in a dish. In this study, after verifying that WDR36 inhibition disrupted polarization in mouse early embryos, it is further demonstrated that WDR36 interference can block human blastoid formation, dominantly hindering the trophectoderm lineage commitment. Both transcriptomics and targeted metabolomics analyses revealed that WDR36 interference downregulated glucose metabolism. WDR36 can interact with glycolytic metabolic protein lactate dehydrogenase A (LDHA), thereby positively regulating glycolysis during the late stage of human blastoid formation. Taken together, the study has established a mechanistic connection between WDR36, glucose metabolism, and cell fate determination during early embryonic lineage commitment, which may provide potential insights into novel therapeutic targets for early adverse pregnancy interventions.PMID:39656902 | DOI:10.1002/advs.202412222

Cardiovasc Res. 2024 Dec 6:cvae250. doi: 10.1093/cvr/cvae250. Online ahead of print.ABSTRACTAIMS: The transcription factor NRF2 is well recognized as a master regulator of antioxidant responses and cytoprotective genes. Previous studies showed that NRF2 enhances resistance of mouse hearts to chronic hemodynamic overload at least in part by reducing oxidative stress. Evidence from other tissues suggests that NRF2 may modulate glucose intermediary metabolism but whether NRF2 has such effects in the heart is unclear. Here, we investigate the role of NRF2 in regulating glucose intermediary metabolism and cardiac function during disease stress.METHODS AND RESULTS: Cardiomyocyte-specific Keap1 knockout (csKeap1KO) mice, deficient in the endogenous inhibitor of NRF2, were used as a novel model of constitutively active NRF2 signaling. Targeted metabolomics and isotopomer analysis were employed in studies with 13C6-glucose in csKeap1KO and wild-type (WT) mice. Pharmacological and genetic approaches were utilized in neonatal rat ventricular cardiomyocytes (NRVM) to explore molecular mechanisms. We found that cardiac-specific activation of NRF2 redirected glucose metabolism towards the pentose phosphate pathway (PPP), a branch pathway of glycolysis, and mitigated pressure overload-induced cardiomyocyte death and cardiac dysfunction. Activation of NRF2 also protected against myocardial infarction-induced DNA damage in remote myocardium and cardiac dysfunction. In vitro, knockdown of Keap1 upregulated PPP enzymes and reduced cell death in NRVM subjected to chronic neurohumoral stimulation. These pro-survival effects were abolished by pharmacological inhibition of the PPP or silencing of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of NRF2 in NRVM increased stress-induced DNA damage which was rescued by supplementing the cells with either NADPH or nucleosides, the two main products of the PPP.CONCLUSIONS: These results indicate that NRF2 regulates cardiac metabolic reprogramming by stimulating the diversion of glucose into the PPP, thereby generating NADPH and providing nucleotides to prevent stress-induced DNA damage and cardiac dysfunction.PMID:39657243 | DOI:10.1093/cvr/cvae250

Eur Heart J. 2024 Dec 4:ehae829. doi: 10.1093/eurheartj/ehae829. Online ahead of print.ABSTRACTCalcific aortic valve disease (CAVD) resulting in aortic stenosis (AS) is the most common form of valvular heart disease, affecting 2% of those over age 65. Those who develop symptomatic severe AS have an average further lifespan of <2 years without valve replacement, and three-quarters of these patients will develop heart failure, undergo valve replacement, or die within 5 years. There are no approved pharmaceutical therapies for AS, due primarily to a limited understanding of the molecular mechanisms that direct CAVD progression in the complex haemodynamic environment. Here, advances in efforts to understand the pathogenesis of CAVD and to identify putative drug targets derived from recent multi-omics studies [including (epi)genomics, transcriptomics, proteomics, and metabolomics] of blood and valvular tissues are reviewed. The recent explosion of single-cell omics-based studies in CAVD and the pathobiological and potential drug discovery insights gained from the application of omics to this disease area are a primary focus. Lastly, the translation of knowledge gained in valvular pathobiology into clinical therapies is addressed, with a particular emphasis on treatment regimens that consider sex-specific, renal, and lipid-mediated contributors to CAVD, and ongoing Phase I/II/III trials aimed at the prevention/treatment of AS are described.PMID:39656785 | DOI:10.1093/eurheartj/ehae829

Int Immunol. 2024 Dec 4:dxae070. doi: 10.1093/intimm/dxae070. Online ahead of print.ABSTRACTIntestinal bacteria play a critical role in the regulation of the host immune system and an imbalance in intestinal bacterial composition induces various host diseases. Therefore, maintaining a balance in the intestinal bacterial composition is crucial for health. Immunoglobulin A (IgA), produced through T cell-dependent and T cell-independent (TI) pathways, is essential for host defense against pathogen invasion and maintaining the balance of intestinal symbiotic bacteria. Interleukin (IL)-5 is constitutively produced by group 2 innate lymphoid cells (ILC2s) and plays a critical role in the survival and proliferation of B cells and eosinophils. Here, we show that the role of IL-5-producing ILC2s in intestinal TI IgA production at steady state using TCRα deficient mice. In this mouse model, ILC2s increased fecal TI IgA levels in a non-inflammatory state in an IL-5-dependent manner. The administration of recombinant IL-33 (rIL-33) increased the amount of TI IgA production, accompanied by an increase in the number of IL-5-producing ILC2s in the large intestine. In addition, rIL-33 treatment increased IL-5-dependent IgA+ cells in isolated lymphoid follicles, the site of TI IgA production. Furthermore, eosinophils recruited by ILC2s were required for the maximal production of IgA in the TI pathway. Moreover, IL-5 increased the frequency of TI IgA-binding intestinal bacteria and was involved in the maintenance of intestinal bacterial composition. These findings indicate that IL-5-producing ILC2s together with eosinophils contribute to TI IgA production. In addition to their role in TI IgA production, IL-5-producing ILC2s may contribute to the homeostasis of intestinal commensal bacteria.PMID:39656643 | DOI:10.1093/intimm/dxae070

J Sep Sci. 2024 Dec;47(23):e70040. doi: 10.1002/jssc.70040.ABSTRACTResearches regarding quality control of ginseng focusing on the lipids are rare. Herein, ultra-high-performance supercritical fluid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPSFC/IM-QTOF-MS) combined with untargeted metabolomic analysis was utilized to holistically characterize and compare the lipidomic difference among 12 Panax-derived herbal medicines. The established UHPSFC/IM-QTOF-MS method, using a Torus 1-AA column with CO2/CH3OH (modifier) as the mobile phase, well resolved the ginseng lipidome within 30 min. The lipid isomers and those easily co-eluted by conventional reversed-phase chromatography got separated, and integrated analyses of the positive-/negative-mode MS data and IM-derived collision cross section (CCS) greatly enhanced lipids identification. By the pattern recognition chemometric analysis of 90 batches of ginseng samples, the root ginseng samples showed significant differences in lipidome composition from those stem/leaf and flower samples. In contrast, red ginseng also contained lipids significantly different from the other root ginseng. Totally 82 potential differential lipids were discovered and identified based on the positive-mode data and 90 ones in the negative mode. Some of these lipid markers might be diagnostic for their authentication. Conclusively, we first report the lipidomic difference among 12 ginseng varieties, and the information obtained can lay foundation for the accurate identification of ginseng from the lipidome level.PMID:39658817 | DOI:10.1002/jssc.70040

J Cheminform. 2024 Dec 10;16(1):140. doi: 10.1186/s13321-024-00935-9.ABSTRACTFlavor is the main factor driving consumers acceptance of food products. However, tracking the biochemistry of flavor is a formidable challenge due to the complexity of food composition. Current methodologies for linking individual molecules to flavor in foods and beverages are expensive and time-consuming. Predictive models based on machine learning (ML) are emerging as an alternative to speed up this process. Nonetheless, the optimal approach to predict flavor features of molecules remains elusive. In this work we present FlavorMiner, an ML-based multilabel flavor predictor. FlavorMiner seamlessly integrates different combinations of algorithms and mathematical representations, augmented with class balance strategies to address the inherent class of the input dataset. Notably, Random Forest and K-Nearest Neighbors combined with Extended Connectivity Fingerprint and RDKit molecular descriptors consistently outperform other combinations in most cases. Resampling strategies surpass weight balance methods in mitigating bias associated with class imbalance. FlavorMiner exhibits remarkable accuracy, with an average ROC AUC score of 0.88. This algorithm was used to analyze cocoa metabolomics data, unveiling its profound potential to help extract valuable insights from intricate food metabolomics data. FlavorMiner can be used for flavor mining in any food product, drawing from a diverse training dataset that spans over 934 distinct food products.Scientific Contribution FlavorMiner is an advanced machine learning (ML)-based tool designed to predict molecular flavor features with high accuracy and efficiency, addressing the complexity of food metabolomics. By leveraging robust algorithmic combinations paired with mathematical representations FlavorMiner achieves high predictive performance. Applied to cocoa metabolomics, FlavorMiner demonstrated its capacity to extract meaningful insights, showcasing its versatility for flavor analysis across diverse food products. This study underscores the transformative potential of ML in accelerating flavor biochemistry research, offering a scalable solution for the food and beverage industry.PMID:39658805 | DOI:10.1186/s13321-024-00935-9

Int J Obes (Lond). 2024 Dec 10. doi: 10.1038/s41366-024-01695-0. Online ahead of print.ABSTRACTBACKGROUND: Human urine is highly favorable for 1H NMR metabolomics analyses of obesity-related diseases, such as non-alcoholic fatty liver, type 2 diabetes, and hyperlipidemia (HL), due to its non-invasiveness and ease of large-scale collection. However, the wide range of intrinsic urine pH (5.5-8.5) results in inevitably chemical shift and signal intensity modulations in the 1H NMR spectra. For patients where acidic urine pH is closely linked to obesity-related disease phenotypes, the pH-dependent modulations complicate the spectral analysis and deteriorate quantifications of urine metabolites.METHODS: We characterized human urine metabolites by NMR at intrinsic urine pH, across urine pH 4.5 to 9.5, to account for pH-dependent modulations. A pH-dependent chemical shift database for quantifiable urine metabolites was generated and integrated into a "pH intelligence" program developed for quantifications of pH-dependent modulations at various pH. The 1H NMR spectra of urines collected from patients with Ob-HL and healthy controls were compared to uncover potential metabolic biomarkers of Ob-HL disease.RESULTS: Three urine metabolites were unveiled by pH-dependent NMR approach, i.e., TMAO, glycine, and pyruvic acid, with VIP score >1.0 and significant q-value < 0.05, that represent as potential biomarkers for discriminating Ob-HL from healthy controls. Further ROC-AUC analyses revealed that TMAO alone achieved the highest diagnostic accuracy (AUC 0.902), surpassed to that obtained by neutralizing pH approach (AUC 0.549) and enabled better recovering potential urine metabolites from the Ob-HL disease phenotypes.CONCLUSIONS: We concluded that 1H NMR-derived urine metabolite profile represents a snapshot that can reveal the physiological condition of humans in either a healthy or diseased state under intrinsic urine pH. We demonstrated a systematic analysis of pH-dependent modulations on the human urine metabolite signals and further developed software for quantification of urine metabolite profiles with high accuracy, enabling the uncovering of potential metabolite biomarkers in clinical diagnosis applications.PMID:39658677 | DOI:10.1038/s41366-024-01695-0

BMJ Open. 2024 Dec 10;14(12):e089038. doi: 10.1136/bmjopen-2024-089038.ABSTRACTINTRODUCTION: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling condition that can affect adolescents during a vulnerable period of development. The underlying biological mechanisms for ME/CFS remain unclear and have rarely been investigated in the adolescent population, despite this period representing an age peak in the overall incidence. The primary objective of this is to provide a foundational set of biological data on adolescent ME/CFS patients. Data generated will be compared with controls and over several time points within each patient to potentially develop a biomarker signature of the disease, identify subsets or clusters of patients, and to unveil the pathomechanisms of the disease.METHODS AND ANALYSIS: This protocol paper outlines a comprehensive, multilevel, longitudinal, observational study in paediatric ME/CFS. ME/CFS patients aged 12-19 years and controls will donate biosamples of urine, blood, and peripheral blood mononuclear cells for an in-depth omics profiling analysis (whole-genome sequencing, metabolomics and quantitative proteomics) while being assessed by gold-standard clinical and neuropsychological measures. ME/CFS patients will then be provided with a take-home kit that enables them to collect urine and blood microsamples during an average day and during days when they are experiencing postexertional malaise. The longitudinal repeated-measures study design is optimal for studying heterogeneous chronic diseases like ME/CFS as it can detect subtle changes, control for individual differences, enhance precision and boost statistical power. The outcomes of this research have the potential to identify biomarker signatures, aid in understanding the underlying mechanisms, and ultimately, improve the lives of children with ME/CFS.ETHICS AND DISSEMINATION: This project was approved by the Royal Children's Hospital's Human Research Ethics Committee (HREC 74175). Findings from this study will be disseminated through peer-reviewed journal publications and presentations at relevant conferences. All participants will be provided with a summary of the study's findings once the project is completed.PMID:39658280 | DOI:10.1136/bmjopen-2024-089038

J Biochem. 2024 Dec 10:mvae084. doi: 10.1093/jb/mvae084. Online ahead of print.ABSTRACTMonogalactosyl diacylglycerol (MGDG) is a major membrane lipid component in plants and is crucial for proper thylakoid functioning. However, MGDG in mammals has not received much attention, partly because of its relative scarcity in mammalian tissues. In addition, the biosynthetic pathway of MGDG in mammals has not been thoroughly analyzed, although some reports have suggested that UGT8, a ceramide galactosyltransferase, has the potential to catalyze MGDG biosynthesis. Here, we successfully captured the endogenous levels of MGDG in HeLa cells using LC-MS/MS-based lipidomics. Cellular MGDG was completely depleted in CRISPR/Cas9-mediated UGT8 knockout HeLa cells. Transient overexpression of UGT8 enhanced MGDG production in HeLa cells, and the corresponding cell lysates displayed MGDG biosynthetic activity in vitro. Site-directed mutagenesis revealed that His358 within the UGT signature sequence was important for its activity. UGT8 was localized in the endoplasmic reticulum and activation of the unfolded protein response by membrane lipid saturation was impaired in UGT8 knockout cells. These results demonstrate that UGT8 is an MGDG synthase in mammals and that UGT8 regulates membrane lipid saturation signals in cells.PMID:39658193 | DOI:10.1093/jb/mvae084

Food Res Int. 2025 Jan;199:115390. doi: 10.1016/j.foodres.2024.115390. Epub 2024 Nov 19.ABSTRACTDietary fiber from coffee peel is rich in bound polyphenols good for human health due to the antioxidant activity. In this study, we evaluated the bound polyphenol release conditions and activities in coffee peel soluble dietary fiber (CPSDF) in the process of in vitro simulation digestion. The CPSDF structure became loose and porous due to simulated digestion but retained the polysaccharide backbone. Widely-targeted metabolomics analysis identified 550 metabolites, with phenolic acids and flavonoids being main differentially expressed metabolites in digested products (82.18% in total). The most significant increase in the 5,7,8,3',4'-pentamethoxyflavanone content and decrease in the 3,5-dihydroxyacetophenone content were observed after digestion (undigested vs S-intestine). Additionally, the changes in antioxidant and enzyme inhibitory activities followed the same pattern as that observed for total phenolic content. The enzyme inhibitory and antioxidant activities of gastric digestion products were greater than those of the oral and small intestinal digestion products. The present work provided the theoretical foundation for developing high-value CPSDF products and reusing coffee peel waste.PMID:39658178 | DOI:10.1016/j.foodres.2024.115390

Food Res Int. 2025 Jan;199:115385. doi: 10.1016/j.foodres.2024.115385. Epub 2024 Nov 19.ABSTRACTGut dysbiosis is a characteristic feature of obesity and targeting gut microbiota presents a promising approach to attenuate obesity. Euglena gracilis polysaccharide (EGP) has emerged as a potential prebiotic capable of promoting health-beneficial bacteria. However, its effects on the gut dysbiosis of obese individuals remain unclear. This study investigated the impacts of EGP on gut microbiota from both non-obese and obese individuals using an in vitro fermentation model. Results showed that EGP significantly altered the gut microbiota composition and metabolism. Specifically, EGP improved the relative abundance of Paeniclostridium, Clostridium_sensu_stricto_1 and Paraclostridium of the non-obese individuals and Providencia, Enterococcus and Bacteroides of the obese individuals. Metabolomics results showed EGP significantly altered the lipid metabolism especially in the obese group with enriched bile secretion and cholesterol metabolism pathways. Noting that acetic acid was significantly increased in both groups, these acetic acid favorable microbiota from non-obese individuals was collected with acetic acid supplementation. Transplantation of these acetic acid-induced microbiota (AAiM) notably improved the richness and diversity of fecal microbiota of the obese individuals, enhancing the growth of probiotics like Bacteroides and Bifidobacterium. Consequently, AAiM significantly restructured macronutrients (including amino acids, carbohydrates and lipids) metabolism of the gut microbiota from obese individuals. Altogether, this study underscores the potential of EGP and acetic acid favorable microbiota in manipulating obesity-associated gut dysbiosis via acetic acid production.PMID:39658176 | DOI:10.1016/j.foodres.2024.115385

Int J Biol Macromol. 2024 Dec 8:138400. doi: 10.1016/j.ijbiomac.2024.138400. Online ahead of print.ABSTRACTHigh molecular weight polysaccharides (GLPH, ≥300 kDa) are the major compounds of Ganoderma lucidum with improving liver function. However, the effect of GLPH on improving acute liver injury (ALI) wasn't revealed. Herein, the ameliorating effects and mechanisms of GLPH were revealed in lipopolysaccharide (LPS)-ALI mice. The results indicated that GLPH intervention (100 mg/kg day) reduced the serum ALT (22.67 ± 6.48 U/L), AST (21.19 ± 7.08 U/L), ALP (56.98 ± 12.71 U/L), GGT (1.48 ± 0.22 U/L) levels in ALI mice (p < 0.01). GLPH activated the hepatic antioxidant enzymes activity [SOD (3.75 ± 1.17 U/mg prot.) and CAT (3.01 ± 0.85 U/mg prot.)] and suppressed the hepatic inflammatory cytokines production [TNF-α (40.14 ± 8.15 pg/mg prot.), IL-1β (35.47 ± 10.90 pg/mg prot.), and IL-6 (8.44 ± 1.71 pg/mg prot.)] by regulating the Nrf2/OH-1 and Tlr4/NF-κB pathway (p < 0.05). Furthermore, GLPH regulated the abundance of Bifidobacterium, Akkermansia, Anaerovorax, and Tyzzerella, which associated with cecal SCFAs, hepatic inflammatory cytokines and antioxidant enzymes. GLPH significantly changed 85 liver metabolites (p < 0.01), which is beneficial for prevent the development of ALI. These results suggested GLPH displayed promising prebiotic properties in relieving ALI, regulating gut microbiota and liver metabolism.PMID:39657883 | DOI:10.1016/j.ijbiomac.2024.138400

J Infect Dis. 2024 Dec 9:jiae532. doi: 10.1093/infdis/jiae532. Online ahead of print.ABSTRACTBACKGROUND: Persons with HIV (PWH) on contemporary antiretroviral therapy (ART) are at elevated risk for developing age-related cardiometabolic diseases. We hypothesized that integrative analysis of cross-tissue, multimodal data from PWH could provide insight into molecular programming that defines cardiometabolic phenotypes in this high-risk group.METHODS: We enrolled 93 PWH without diabetes who were virologically suppressed on contemporary ART and obtained measures of insulin resistance, glucose intolerance, and adiposity. We performed circulating lipidomics, proteomics, and metabolomics, as well as subcutaneous adipose tissue (SAT) bulk transcriptomics, and used multiomics factor analysis (MOFA) to perform integrative analyses of these datasets.RESULTS: The median age was 43 years, median body mass index 30.8 kg/m2, 81% were male, and 56% were self-identified non-Hispanic White. We identified a specific MOFA factor associated with visceral adipose tissue volume (ρ = -0.43), homeostasis model assessment 2 insulin resistance score (ρ = -0.52), liver density (ρ = 0.43), and other cardiometabolic risk factors, which explained more variance in the SAT transcriptome and circulating lipidome compared with the circulating proteome and metabolome. Gene set enrichment analysis of this factor showed extracellular matrix and inflammatory pathways that primarily mapped to SAT myeloid cells and adipose progenitor cells using single-cell deconvolution. Lipidomic analysis showed that this factor was significantly enriched for triacylglycerol and diacylglycerol species.CONCLUSIONS: Our multiomic analysis demonstrated coordinated, multitissue molecular reprogramming in virologically suppressed PWH with elevated cardiometabolic disease risk. Longitudinal studies of PWH with assessments of adipose tissue and lipid handling are necessary to understand mechanisms of cardiometabolic disease in PWH. Clinical Trials Registration. NCT04451980.PMID:39657693 | DOI:10.1093/infdis/jiae532

Cell Metab. 2024 Dec 5:S1550-4131(24)00453-4. doi: 10.1016/j.cmet.2024.11.007. Online ahead of print.ABSTRACTChronological age is a crucial risk factor for diseases and disabilities among older adults. However, individuals of the same chronological age often exhibit divergent biological aging states, resulting in distinct individual risk profiles. Chronological age estimators based on omics data and machine learning techniques, known as aging clocks, provide a valuable framework for interpreting molecular-level biological aging. Metabolomics is an intriguing and rapidly growing field of study, involving the comprehensive profiling of small molecules within the body and providing the ultimate genome-environment interaction readout. Consequently, leveraging metabolomics to characterize biological aging holds immense potential. The aim of this review was to provide an overview of metabolomics approaches, highlighting the establishment and interpretation of metabolomic aging clocks while emphasizing their strengths, limitations, and applications, and to discuss their underlying biological significance, which has the potential to drive innovation in longevity research and development.PMID:39657675 | DOI:10.1016/j.cmet.2024.11.007

Cell Rep Med. 2024 Dec 5:101853. doi: 10.1016/j.xcrm.2024.101853. Online ahead of print.ABSTRACTMetabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health threat globally. Management of patients afflicted with MASLD and research in this domain are limited by the lack of robust well-established non-invasive biomarkers for diagnosis, prognostication, and monitoring. The circulating metabolome reflects both the systemic metabo-inflammatory milieu and changes in the liver in affected individuals. In this review we summarize the available literature on changes in the different components of the metabolome in MASLD with a focus on changes that are linked to the presence of underlying steatohepatitis, severity of disease activity, and fibrosis stage. We further summarize the existing literature around biomarker panels that are derived from interrogation of the metabolome. Their relevance to disease biology and utility in practice are also discussed. We further highlight potential direction for future studies particularly to ensure they are fit for purpose and suitable for widespread use.PMID:39657668 | DOI:10.1016/j.xcrm.2024.101853

Biomed Pharmacother. 2024 Dec 9;181:117731. doi: 10.1016/j.biopha.2024.117731. Online ahead of print.ABSTRACTThe interplay between the dysbiotic microbiota and bile acids is a critical determinant for development of a dysregulated immune system in inflammatory bowel disease (IBD). Here we have investigated the fecal bile acid metabolome, gut microbiota composition, and immune responses in IBD patients and murine models of colitis and found that IBD associates with an elevated excretion of primary bile acids while secondary, allo- and oxo- bile acids were reduced. These changes correlated with the disease severity, mucosal expression of pro-inflammatory cytokines and chemokines, and reduced inflow of anti-inflammatory macrophages and Treg in the gut. Analysis of bile acids metabolome in the feces allowed the identification of five bile acids: 3-oxo-DCA, 3-oxo-LCA, allo-LCA, iso-allo-LCA and 3-oxo-UDCA, whose excretion was selectively decreased in IBD patients and diseased mice. By transactivation assay and docking calculations all five bile acids were shown to act as GPBAR1 agonists and RORγt inverse agonists, skewing Th17/Treg ratio and macrophage polarization toward an M2 phenotype. In a murine model of colitis, administration of 3-oxo-DCA suffices to reverse colitis development and intestinal dysbiosis in a GPBAR1-dependent manner. In vivo administration of 3-oxo-DCA to colitic mice also reverses disease severity and RORγt activation induced by a RORγt agonist and IL-23, a Th17 inducing cytokine. These results demonstrated that intestinal excretion of 3-oxoDCA, a dual GPBAR1 agonist and RORγt inverse agonist, is reduced in IBD and in models of colitis and its restitution protects against colitis development, highlighting a potential role for this agent in IBD management.PMID:39657506 | DOI:10.1016/j.biopha.2024.117731

J Hazard Mater. 2024 Dec 7;485:136818. doi: 10.1016/j.jhazmat.2024.136818. Online ahead of print.ABSTRACTResidual concentrations of antibiotics in water can reach ng mL-1 - µg mL-1 levels, which pose high risks to crops during irrigation; however, the interactions between rice and antibiotics, as well as the defense mechanisms of rice at their early growth phase remain unclear. In this study, we investigated the uptake dynamics of a ubiquitously found antibiotic, ciprofloxacin (CIP) at 0.1, 1, 6.5, and 20 µg mL-1 in rice seedlings. We found gradually bioaccumulated CIP induced significant physiological changes including inhibited growth of roots and leaves of rice seedlings, and decreased pigment contents, which can be caused by disrupted homeostasis of reactive oxygen species. Integrating roots transcriptomics, metabolomics, and validation experiments, we found that rice seedlings synthesized more gibberellins to trigger the expression of transcription factors such as group VII ethylene response factors, which induced metabolic reprogramming to yield more fatty acids derivates. These compounds including eicosanoids, isoprenoids, and fatty acids and conjugates can act as signaling molecules, as well as antioxidants and energy sources to achieve rice recovery. This conclusion is supported by the evidence showing that adding gibberellins in rice seedlings culture decreased the accumulated CIP and improved rice growth; whilst, disrupting gibberellin signaling pathway using paclobutrazol as an inhibitor increased uptaken CIP in both roots and leaves with augmenting the antibiotic stress on rice. This study has demonstrated a gibberellin-based defense mechanism in rice for defense of CIP stress, which might have significant environmental applications since we can add minor gibberellins to reduce bioaccumulated CIP with simultaneously promoting rice growth at their early phases.PMID:39657495 | DOI:10.1016/j.jhazmat.2024.136818

Microbiol Res. 2024 Dec 6;292:127995. doi: 10.1016/j.micres.2024.127995. Online ahead of print.ABSTRACTThis review provides a comprehensive analysis of the intricate architecture of bacterial sensing systems, with a focus on signal transduction mechanisms and their critical roles in microbial physiology. It highlights quorum sensing (QS), quorum quenching (QQ), and quorum sensing interference (QSI) as fundamental processes driving bacterial communication, influencing gene expression, biofilm formation, and interspecies interactions. The analysis explores the importance of diffusible signal factors (DSFs) and secondary messengers such as cAMP and c-di-GMP in modulating microbial behaviors. Additionally, cross-kingdom signaling, where bacterial signals impact host-pathogen dynamics and ecological balance, is systematically reviewed. This review introduces "signalomics", an novel interdisciplinary framework integrating genomics, proteomics, and metabolomics to offer a holistic framework for understanding microbial communication and evolution. These findings hold significant implications for various domains, including food preservation, agriculture, and human health.PMID:39657399 | DOI:10.1016/j.micres.2024.127995