PubMed

Front Genet. 2023 Jan 9;13:1084609. doi: 10.3389/fgene.2022.1084609. eCollection 2022.ABSTRACTMetabolic reprogramming is an important hallmark of malignant tumors. Serine is a non-essential amino acid involved in cell proliferation. Serine metabolism, especially the de novo serine synthesis pathway, forms a metabolic network with glycolysis, folate cycle, and one-carbon metabolism, which is essential for rapidly proliferating cells. Owing to the rapid development in metabolomics, abnormal serine metabolism may serve as a biomarker for the early diagnosis and pathological typing of tumors. Targeting serine metabolism also plays an essential role in precision and personalized cancer therapy. This article is a systematic review of de novo serine biosynthesis and the link between serine and folate metabolism in tumorigenesis, particularly in lung cancer. In addition, we discuss the potential of serine metabolism to improve tumor treatment.PMID:36699468 | PMC:PMC9868472 | DOI:10.3389/fgene.2022.1084609

Front Vet Sci. 2023 Jan 9;9:1037327. doi: 10.3389/fvets.2022.1037327. eCollection 2022.ABSTRACTBACKGROUND AND AIMS: The metabolomic profile of a biofluid can be affected by age, and thus provides detailed information about the metabolic alterations in biological processes and reflects the in trinsic rule regulating the growth and developmental processes.METHODS: To systemically investigate the characteristics of multiple metabolic profiles associated with canine growth, we analyzed the metabolomics in the plasma and urine samples from 15 young and 15 adult beagle dogs via UHPLC-Q-TOFMS-based metabolomics. Blood routine and serum biochemical analyses were also performed on fasting blood samples.RESULTS: The metabolomics results showed remarkable differences in metabolite fingerprints both in plasma and urine between the young and adult groups. The most obvious age-related metabolite alterations include decreased serumlevels of oxoglutaric acid and essential amino acids and derivatives but increased levels of urine levels of O-acetylserine. These changes primarily involved in amino acid metabolism and bile secretion pathways. We also found that the levels of glutamine were consistently higher in both serum and urine of adults, while N-acetylhistamine and uracil concentrations were much lower in the adult group compared to younger ones.CONCLUSION: Our study provides a whole metabolic profile of serum and urine characteristics of young and adult canines, identifying several metabolites that were significantly associated with age change, which provides theoretical support for the nutrition-related research and age-related homeostasis maintenance in dogs.PMID:36699333 | PMC:PMC9868312 | DOI:10.3389/fvets.2022.1037327

Curr Res Food Sci. 2023 Jan 12;6:100440. doi: 10.1016/j.crfs.2023.100440. eCollection 2023.ABSTRACTMany people peel fruits, commonly persimmon, grape, apple, and peach, before eating as table fruits. Differences of bioactive compounds between peels and pulps of daily fruits are widely known but limited to individual compound because understanding of differences in their global metabolites is lack. We employed 1H NMR-based metabolomics to explore the global metabolite differences between their peels and pulps from the fruits, which included changes of diverse metabolites in persimmon after harvest ripening. Of diverse metabolites observed among the fruits tested, various health-beneficial metabolites were present in the peels rather than the pulps and their classes were dependent on the type of fruit: gallocatechin, epicatechin and epigallocatehin only in persimmon, apple, and peach, respectively; quercetin only in persimmon and apple; kaempferol only in persimmon; chlorogenic acid only in grape and peach; neochlorogenic acid only in apple and peach; p-coumaric acid only in grape; phloridzin and catechin only in apple. These metabolites in the peels of each fruits were strongly correlated with free radical-scavenging activity and delay of carbohydrate digestion. Therefore, intake of whole fruits, rather than removal of their peels, were recommended for potential improvement of healthy lifespan and human wellness. This study highlights the critical role of metabolomic studies in simultaneous determinations of diverse and intrinsic metabolites in different types of fruits and thus providing a strategy for healthy eating habits of daily fruits.PMID:36699116 | PMC:PMC9868340 | DOI:10.1016/j.crfs.2023.100440

Comput Struct Biotechnol J. 2023 Jan 4;21:869-878. doi: 10.1016/j.csbj.2023.01.001. eCollection 2023.ABSTRACTThe natural world is constantly changing, and planetary boundaries are issuing severe warnings about biodiversity and cycles of carbon, nitrogen, and phosphorus. In other views, social problems such as global warming and food shortages are spreading to various fields. These seemingly unrelated issues are closely related, but it can be said that understanding them in an integrated manner is still a step away. However, progress in analytical technologies has been recognized in various fields and, from a microscopic perspective, with the development of instruments including next-generation sequencers (NGS), nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC/MS), and liquid chromatography-mass spectrometry (LC/MS), various forms of molecular information such as genome data, microflora structure, metabolome, proteome, and lipidome can be obtained. The development of new technology has made it possible to obtain molecular information in a variety of forms. From a macroscopic perspective, the development of environmental analytical instruments and environmental measurement facilities such as satellites, drones, observation ships, and semiconductor censors has increased the data availability for various environmental factors. Based on these background, the role of computational science is to provide a mechanism for integrating and understanding these seemingly disparate data sets. This review describes machine learning and the need for structural equations and statistical causal inference of these data to solve these problems. In addition to introducing actual examples of how these technologies can be utilized, we will discuss how to use these technologies to implement environmentally friendly technologies in society.PMID:36698969 | PMC:PMC9860287 | DOI:10.1016/j.csbj.2023.01.001

Front Neurol. 2023 Jan 9;13:1101524. doi: 10.3389/fneur.2022.1101524. eCollection 2022.ABSTRACTMetabolomics has evolved into a particularly useful tool to study interactions between metabolites and serves as an aid in unraveling the complexity of entire metabolomes. Nonetheless, it is increasingly viewed as a methodology with practical applications in the clinical setting, where identifying and quantifying biomarkers of interest could prove useful for diagnostics. Starting from a concise overview of the most prominent analytical techniques employed in metabolomics, herein we present a review of its application in studies of brain metabolism and cerebrovascular diseases, paying most attention to its uses in researching aneurysmal subarachnoid hemorrhage. Both animal models and human studies are considered, and metabolites identified as potential biomarkers are highlighted.PMID:36698893 | PMC:PMC9868237 | DOI:10.3389/fneur.2022.1101524

Front Nutr. 2023 Jan 9;9:1008730. doi: 10.3389/fnut.2022.1008730. eCollection 2022.ABSTRACTINTRODUCTION: During the holy month of Ramadan, adult healthy Muslims are mandated to abstain from dawn to sunset, with free eating at night hours that may extend up to 12 h. The current work was designed to investigate the metabolomics changes incurred upon the observance of Ramadan diurnal intermittent fasting (RDIF).METHODS: Twenty-five metabolically healthy participants with overweight and obesity (7 females and 18 males, with a mean age of 39.48 ± 10.0 years) were recruited for the study and were followed before and at the end of RDIF month. Dietary, anthropometric, biochemical, and physical activity assessments were performed before and at the end of the fasting month. The metabolomic assay was performed using liquid chromatography-mass spectrometry for the two-time points.RESULTS AND DISCUSSION: Metabolomics assay revealed a significant reduction in a few metabolites. The analysis revealed that 27 metabolites differed significantly (P < 0.05) between pre-and post-RDIF. Among the differentially abundant metabolites, 23 showed a decrease with fasting, these included several amino acids such as aspartame, tryptophan, phenylalanine, histidine, and other metabolites including valeric acid, and cortisol. On the other hand, only four metabolites showed increased levels after RDIF including traumatic acid, 2-pyrrolidinone, PC[18:1(9Z)/18:1(9Z)], and L-sorbose. The MetaboAnalyst® platform reported that the top enriched metabolic pathways included: (1) histidine metabolism; (2) folate biosynthesis (3) phenylalanine, tyrosine, and tryptophan biosynthesis; (4) aminoacyltRNA biosynthesis; (5) caffeine metabolism; (6) vitamin B6 metabolism; and several other pathways relating to lipid metabolisms such as arachidonic acid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. In conclusion, RDIF entails significant changes in various metabolic pathways that reflect different dietary and lifestyle behaviors practiced during the fasting month.PMID:36698470 | PMC:PMC9868699 | DOI:10.3389/fnut.2022.1008730

Front Nutr. 2023 Jan 9;9:1078060. doi: 10.3389/fnut.2022.1078060. eCollection 2022.ABSTRACTBACKGROUND: Mushrooms are rich in dietary fiber, and fiber intake has been reported to increase the levels of short-chain fatty acids (SCFAs). It has also been reported that SCFAs promote immunoglobulin A (IgA) production, indicating involvement in systemic immunity.OBJECTIVES: The objective of this study was to evaluate the effects of mushroom consumption on the amount of intestinal IgA. We also aimed to comprehensively evaluate the gut microbiota and intestinal metabolome and to conduct an exploratory analysis of their relationship with IgA.METHODS: Healthy adults (n = 80) were enrolled in a parallel group trial. Participants consumed a diet with mushrooms or a placebo diet once daily for 4 weeks. Gut microbiota profiles were assessed by sequencing the bacterial 16S ribosomal RNA-encoding gene. Intestinal metabolome profiles were analyzed using capillary electrophoresis-time of flight mass spectrometry (CE-TOFMS).RESULTS: Mushroom consumption tended to increase IgA levels at 4 weeks of consumption compared to those in the control group (p = 0.0807; Hedges' g = 0.480). The mushroom group had significantly higher levels of intestinal SCFAs, such as butyrate and propionate, than the control group (p = 0.001 and 0.020; Hedges' g = 0.824 and 0.474, respectively). Correlation analysis between the changes in the amount of intestinal IgA and the baseline features of the intestinal environment showed that the increasing amount of intestinal IgA was positively correlated with the baseline levels of SCFAs (Spearman's R = 0.559 and 0.419 for butyrate and propionate, respectively).CONCLUSION: Consumption of mushrooms significantly increased the intestinal SCFAs and IgA in some subjects. The increase in intestinal IgA levels was more prominent in subjects with higher SCFA levels at baseline. This finding provides evidence that mushroom alters the intestinal environment, but the intensity of the effect still depends on the baseline intestinal environment. This trial was registered at www.umin.ac.jp as UMIN000043979.PMID:36698463 | PMC:PMC9868702 | DOI:10.3389/fnut.2022.1078060

Adv Sci (Weinh). 2023 Jan 25:e2207170. doi: 10.1002/advs.202207170. Online ahead of print.ABSTRACTGut microbiota-mediated colonization resistance (CR) is crucial in protecting the host from intestinal infections. Sleep deprivation (SD) is an important contributor in the disturbances of intestinal homeostasis. However, whether and how SD affects host CR remains largely unknown. Here, it is shown that SD impairs intestinal CR in mice, whereas nicotinamide mononucleotide (NMN) supplementation restores it. Microbial diversity and metabolomic analyses suggest that gut microbiota and metabolite profiles in SD-treated mice are highly shaped, whereas NMN reprograms these differences. Specifically, the altered gut microbiota in SD mice further incurs the disorder of secondary bile acids pool accompanied by a decrease in deoxycholic acid (DCA). Conversely, NMN supplementation retakes the potential benefits of DCA, which is associated with specific gut microbiota involved in primary bile acids metabolic flux. In animal models of infection, DCA is effective in preventing and treating bacterial infections when used alone or in combination with antibiotics. Mechanistically, DCA alone disrupts membrane permeability and aggravates oxidative damage, thereby reducing intestinal pathogen burden. Meanwhile, exogenous DCA promotes antibiotic accumulation and destroys oxidant-antioxidant system, thus potentiating antibiotic efficacy. Overall, this work highlights the important roles of gut microbiota and bile acid metabolism in the maintenance of intestinal CR.PMID:36698264 | DOI:10.1002/advs.202207170

J Nanobiotechnology. 2023 Jan 25;21(1):29. doi: 10.1186/s12951-023-01788-4.ABSTRACTLiver fibrosis is a chronic liver disease with the presence of progressive wound healing response caused by liver injury. Currently, there are no approved therapies for liver fibrosis. Exosomes derived from human adipose mesenchymal stem cells (hADMSCs-Exo) have displayed a prominent therapeutic effect on liver diseases. However, few studies have evaluated therapeutic effect of hADMSCs-Exo in liver fibrosis and cirrhosis, and its precise mechanisms of action remain unclear. Herein, we investigated anti-fibrotic efficacy of hADMSCs-Exo in vitro and in vivo, and identified important metabolic changes and the detailed mechanism through transcriptomic and metabolomic profiling. We found hADMSCs-Exo could inhibit the proliferation of activated hepatic stellate cells through aggravating apoptosis and arresting G1 phase, effectively inhibiting the expression of profibrogenic proteins and epithelial-to-mesenchymal transition (EMT) in vitro. Moreover, it could significantly block collagen deposition and EMT process, improve liver function and reduce liver inflammation in liver cirrhosis mice model. The omics analysis revealed that the key mechanism of hADMSCs-Exo anti-hepatic fibrosis was the inhibition of PI3K/AKT/mTOR signaling pathway and affecting the changes of metabolites in lipid metabolism, and mainly regulating choline metabolism. CHPT1 activated by hADMSCs-Exo facilitated formation and maintenance of vesicular membranes. Thus, our study indicates that hADMSCs-Exo can attenuate hepatic stellate cell activation and suppress the progression of liver fibrosis, which holds the significant potential of hADMSCs-Exo for use as extracellular nanovesicles-based therapeutics in the treatment of liver fibrosis and possibly other intractable chronic liver diseases.PMID:36698192 | DOI:10.1186/s12951-023-01788-4

Commun Chem. 2022 Dec 19;5(1):162. doi: 10.1038/s42004-022-00778-1.ABSTRACTMass spectrometry-based untargeted lipidomics has revealed the lipidome atlas of living organisms at the molecular species level. Despite the double bond (C = C) position being a crucial factor in biological system, the C = C defined structures have not yet been characterized comprehensively. Here, we present an approach for C = C position-resolved untargeted lipidomics using a combination of oxygen attachment dissociation and computational mass spectrometry to increase the annotation rate. We validated the accuracy of our platform as per the authentic standards of 85 lipids and the biogenic standards of 52 molecules containing polyunsaturated fatty acids (PUFAs) from the cultured cells fed with various fatty acid-enriched media. By analyzing human and mice-derived samples, we characterized 648 unique lipids with the C = C position-resolved level encompassing 24 lipid subclasses defined by LIPIDMAPS. Our platform also illuminated the unique profiles of tissue-specific lipids containing n-3 and/or n-6 very long-chain PUFAs (carbon [Formula: see text] 28 and double bonds [Formula: see text] 4) in the eye, testis, and brain of the mouse.PMID:36698019 | DOI:10.1038/s42004-022-00778-1

Sci Rep. 2023 Jan 25;13(1):1381. doi: 10.1038/s41598-022-25491-w.ABSTRACTThe use of green feed for livestock breeding is an important strategy to encounter both the increasing demand for animal derived products and the perceptions of the consumers regarding animal welfare and sustainability. The aim of this study was to compare different feeding strategies in lactating water buffaloes by using a metabolomic approach. The study was carried out on 32 milking buffaloes that were randomly divided into two groups for a total period of 90 days (3 sampling times). DD Group (dry diet) received a standard total mixed ratio (TMR) characterized by dry forages and concentrates; ZG Group (zero grazing) fed an isoenergetic and isoproteic diet obtained using 30% of sorghum as green forage. Samples of milk and rumen fluid were analyzed by liquid chromatography-mass spectrometry (LC-MS) techniques. Data analyses revealed the presence of several differentially accumulated metabolites and among these, ten compounds were putatively identified in milk samples (i.e. L-carnitine, acetylcarnitine, propionylcarnitine, butyrylcarnitine, 2-methylbutyroylcarnitine, 2-hexenoylcarnitine, hexanoylcarnitine, glycerophosphocholine, δ-valerobetaine and γ-butyrobetaine) and four in rumen fluid (3-(2-hydroxyphenyl) propanoate, Indole-3-acrylic acid, oleamide (cis-9,10-octadecenoamide) and 20-carboxy-leukotriene B4). The modulation of these molecules in buffalo milk is significantly related to the green/dry based feeding and some the natural compound detected could be considered as health-promoting nutrients.PMID:36697476 | DOI:10.1038/s41598-022-25491-w

Nat Commun. 2023 Jan 25;14(1):412. doi: 10.1038/s41467-023-36069-z.NO ABSTRACTPMID:36697392 | DOI:10.1038/s41467-023-36069-z

Anal Chim Acta. 2023 Feb 22;1243:340824. doi: 10.1016/j.aca.2023.340824. Epub 2023 Jan 11.ABSTRACTThe term 'Big Data' has recently attracted much attention in science. Working with big data sets can be both challenging and rewarding. The complexity and big data sets make the analysis difficult to deal with, and the increasing volume of data sets requires the development of new practical methods for their handling. In this contribution, we explored the efficient data reduction-multivariate curve resolution (EDR-MCR) strategy based on the convex hull theory for quantitative and qualitative analysis of large chemical data sets. For the quantitative example, the potential of the EDR-MCR method for selecting a representative calibration set was investigated, and the results were compared with the widely used Kennard-Stone (KS) algorithm. The EDR-MCR strategy strongly limits the number of calibration samples with a high potency of prediction performance. The priority of EDR-MCR over KS is its ability to find informative variables and eliminate redundant features. Moreover, the EDR-MCR strategy was also applied for the qualitative analysis of a large-scale metabolomic data set. The comparable analysis results of EDR-MCR with the region of interest (ROI) method confirmed the ability of this method for quantitative analysis of big mass spectrophotometer data sets.PMID:36697179 | DOI:10.1016/j.aca.2023.340824

J Hazard Mater. 2023 Jan 20;447:130831. doi: 10.1016/j.jhazmat.2023.130831. Online ahead of print.ABSTRACTLegacy per- and polyfluoroalkyl substances (PFASs) are a worldwide health concern due to their potential bioaccumulation and toxicity in humans. A variety of perfluoroether carboxylic acids (PFECAs) have been developed as next-generation replacements of legacy PFASs. However, information regarding their possible environmental and human health risks is limited. In the present study, we explored the effects of PFECAs on mice based on long-term exposure to environmentally relevant doses of perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoDA). Results showed that PFECAs exposure suppressed many cellular stress signals and resulted in hepatomegaly. PFO5DoDA acted as an agonist of the peroxisome proliferator-activated receptor (PPAR) in vitro and modulated PPAR-dependent gene expression in the liver. Importantly, PFECAs had an inhibitory effect on the glucocorticoid receptor (GR), which may contribute to the extensive suppression of stress signals. Of note, the GR suppression induced by PFECAs was not reported by legacy perfluorooctanoic acid (PFOA). PFO5DoDA-induced changes in both GR and PPAR signals remodeled hepatic metabolic profiles, including decreased fatty acids and amino acids and increased β-oxidation. Mechanistically, PFO5DoDA inhibited GR transactivation by degradation of GR proteins. Our results emphasize the potential risk of PFECAs to human health, which were introduced to ease concerns regarding legacy PFASs.PMID:36696776 | DOI:10.1016/j.jhazmat.2023.130831

Food Chem. 2023 Jan 12;411:135478. doi: 10.1016/j.foodchem.2023.135478. Online ahead of print.ABSTRACTPotential effects of metabiotics (probiotics effector molecules or signaling factors), pharmabiotics (pro-functional metabolites produced by gut microbiota (GMB)) and postbiotics (multifunctional metabolites and structural compounds of food-grade microorganisms) on GMB have been rarely reviewed. These multifunctional components have several promising capabilities for prevention, alleviation and treatment of some diseases or disorders. Correlations between these essential biotics and GMB are also very interesting and important in human health and nutrition. Furthermore, these natural bioactives are involved in modulation of the immune function, control of metabolic dysbiosis and regulation of the signaling pathways. This review discusses the potential of meta/pharma/post-biotics as new classes of pharmaceutical agents and their effective mechanisms associated with GMB-host cell to cell communications with therapeutic benefits which are important in balance and the integrity of the host microbiome. In addition, cutting-edge findings about bioinformatics /metabolomics analyses related to GMB and these essential biotics are reviewed.PMID:36696721 | DOI:10.1016/j.foodchem.2023.135478

Food Chem. 2023 Jan 18;411:135498. doi: 10.1016/j.foodchem.2023.135498. Online ahead of print.ABSTRACTConsumers around the world prefer high quality table grapes. To achieve higher quality traits at ripening, grapevine producers apply different plant growth regulators. The synthetic cytokinin forchlorfenuron N-(2-chloro-4-pyridinyl)-N'-phenylurea (CPPU) is widely used, its effect on grape quality is poorly understood. We hypothesized that the use of CPPU in pre-flowering can lead to changes in the metabolism that affects grape quality at harvest. Therefore, we investigated the role of CPPU applications on the quality of grapes by integrating proteomics and metabolomics. CPPU-treated grapevines showed a significant increase in berry size and firmness. Proteomic analyses indicated that CPPU-treated berries accumulated enzymes associated with carbohydrate metabolism, glycolysis, and tricarboxylic acid (TCA) cycle at harvest. Metabolomic analyses showed shifts in the abundance of compounds associated with carbohydrate metabolism and TCA cycle in CPPU-treated grapes. These findings suggest that CPPU applications modulate central carbon metabolism, improving grape berry quality.PMID:36696718 | DOI:10.1016/j.foodchem.2023.135498

Arch Toxicol. 2023 Jan 25. doi: 10.1007/s00204-023-03445-z. Online ahead of print.ABSTRACTT-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals.PMID:36695871 | DOI:10.1007/s00204-023-03445-z

Dis Model Mech. 2023 Jan 1;16(1):dmm049727. doi: 10.1242/dmm.049727. Epub 2023 Jan 25.ABSTRACTParkinson's disease (PD), an age-dependent neurodegenerative disease, is characterised by the selective loss of dopaminergic neurons in the substantia nigra (SN). Mitochondrial dysfunction is a hallmark of PD, and mutations in PINK1, a gene necessary for mitochondrial fitness, cause PD. Drosophila melanogaster flies with pink1 mutations exhibit mitochondrial defects and dopaminergic cell loss and are used as a PD model. To gain an integrated view of the cellular changes caused by defects in the PINK1 pathway of mitochondrial quality control, we combined metabolomics and transcriptomics analysis in pink1-mutant flies with human induced pluripotent stem cell (iPSC)-derived neural precursor cells (NPCs) with a PINK1 mutation. We observed alterations in cysteine metabolism in both the fly and human PD models. Mitochondrial dysfunction in the NPCs resulted in changes in several metabolites that are linked to cysteine synthesis and increased glutathione levels. We conclude that alterations in cysteine metabolism may compensate for increased oxidative stress in PD, revealing a unifying mechanism of early-stage PD pathology that may be targeted for drug development. This article has an associated First Person interview with the first author of the paper.PMID:36695500 | DOI:10.1242/dmm.049727

J Crohns Colitis. 2023 Jan 24:jjad012. doi: 10.1093/ecco-jcc/jjad012. Online ahead of print.ABSTRACTBiomarkers to guide clinical decision-making at diagnosis of inflammatory bowel disease (IBD) are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. Forty-seven individual glycan peaks were analysed using ultra-high performance liquid chromatography identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio (HR) 25.9, p=1.1×10-12; 95% confidence interval (CI), 8.52-78.78). Application to an independent replication cohort of 54 IBD patients yielded a HR of 5.1 (p=1.1×10-5; 95% CI, 2.54-10.1). These data demonstrate the prognostic capacity of serum N-glycan biomarkers and represent a step towards personalized medicine in IBD.PMID:36694402 | DOI:10.1093/ecco-jcc/jjad012

Crit Rev Clin Lab Sci. 2023 Jan 24:1-20. doi: 10.1080/10408363.2023.2166013. Online ahead of print.ABSTRACTThe currently available biomarkers generally lack the specificity and sensitivity needed for the diagnosis and follow-up of patients with mitochondrial diseases (MDs). In this group of rare genetic disorders (mutations in approximately 350 genes associated with MDs), all clinical presentations, ages of disease onset and inheritance types are possible. Blood, urine, and cerebrospinal fluid surrogates are well-established biomarkers that are used in clinical practice to assess MD. One of the main challenges is validating specific and sensitive biomarkers for the diagnosis of disease and prediction of disease progression. Profiling of lactate, amino acids, organic acids, and acylcarnitine species is routinely conducted to assess MD patients. New biomarkers, including some proteins and circulating cell-free mitochondrial DNA, with increased diagnostic specificity have been identified in the last decade and have been proposed as potentially useful in the assessment of clinical outcomes. Despite these advances, even these new biomarkers are not sufficiently specific and sensitive to assess MD progression, and new biomarkers that indicate MD progression are urgently needed to monitor the success of novel therapeutic strategies. In this report, we review the mitochondrial biomarkers that are currently analyzed in clinical laboratories, new biomarkers, an overview of the most common laboratory diagnostic techniques, and future directions regarding targeted versus untargeted metabolomic and genomic approaches in the clinical laboratory setting. Brief descriptions of the current methodologies are also provided.PMID:36694353 | DOI:10.1080/10408363.2023.2166013