PubMed

Metabolites. 2023 Jan 3;13(1):75. doi: 10.3390/metabo13010075.ABSTRACTMetabolomics based on two-dimensional gas chromatography coupled with mass spectrometry is making high demands on accuracy at all stages of sample preparation, up to the storage and injection into the analytical system. In high sample flow conditions, good repeatability in peak areas and a list of detectable metabolites is sometimes challenging to obtain. In this research, we successfully obtained good repeatability for the peak areas of MSFTA-derivatives of 29 core blood plasma metabolites. Six different strategies of storage and injection were investigated and evaluated for the reproducibility of the obtained data. As the essential factors, we considered popular GC-MS syringe washing solvents (methanol and pyridine); storage conditions (freshly prepared samples and stored for 24 h in ambient temperature or in the refrigerator); scheme of injection (one injection per intact vial or three sequential injections per vial). Our GC×GC-MS results demonstrated that the usage of pyridine as a syringe wash solvent and triple injecting the sample from the same vial was the most appropriate for minimizing the coefficient of variation (CV) of the results obtained (in general, <10%). The prolonged storage of samples does not have a noticeable effect on the change in the areas of chromatographic peaks of metabolites, although it reduces CV in some cases. These storage and injection recommendations can be used in future study protocols for the GC×GC-MS analysis of blood plasma.PMID:36677000 | DOI:10.3390/metabo13010075

Metabolites. 2023 Jan 2;13(1):71. doi: 10.3390/metabo13010071.ABSTRACTAlternaria leaf blight, caused by the fungus Alternaria dauci, is the most damaging foliar disease of carrot. Some carrot genotypes exhibit partial resistance to this pathogen and resistance Quantitative Trait Loci (rQTL) have been identified. Co-localization of metabolic QTL and rQTL identified camphene, α-pinene, α-bisabolene, β-cubebene, caryophyllene, germacrene D and α-humulene as terpenes potentially involved in carrot resistance against ALB. By combining genomic and transcriptomic analyses, we identified, under the co-localization regions, terpene-related genes which are differentially expressed between a resistant and a susceptible carrot genotype. These genes include five terpene synthases and twenty transcription factors. In addition, significant mycelial growth inhibition was observed in the presence of α-humulene and caryophyllene.PMID:36676996 | DOI:10.3390/metabo13010071

Metabolites. 2023 Jan 1;13(1):70. doi: 10.3390/metabo13010070.ABSTRACTArsenic (As) exposure causes numerous adverse health effects, which can be reduced by the nutrients involved in the metabolism of iAs (inorganic As). This study was carried out on two groups of copper-smelting workers: WN, workers with a urinary total arsenic (tAs) concentration within the norm (n = 75), and WH, workers with a urinary tAs concentration above the norm (n = 41). This study aimed to analyze the association between the intake level of the nutrients involved in iAs metabolism and the signal intensity of the metabolites that were affected by iAs exposure. An untargeted metabolomics analysis was carried out on urine samples using liquid chromatography-mass spectrometry, and the intake of the nutrients was analyzed based on 3-day dietary records. Compared with the WN group, five pathways (the metabolism of amino acids, carbohydrates, glycans, vitamins, and nucleotides) with twenty-five putatively annotated metabolites were found to be increased in the WH group. In the WN group, the intake of nutrients (methionine; vitamins B2, B6, and B12; folate; and zinc) was negatively associated with six metabolites (cytosine, D-glucuronic acid, N-acetyl-D-glucosamine, pyroglutamic acid, uridine, and urocanic acid), whereas in the WH group, it was associated with five metabolites (D-glucuronic acid, L-glutamic acid, N-acetyl-D-glucosamine, N-acetylneuraminic acid, and uridine). Furthermore, in the WH group, positive associations between methionine, folate, and zinc intake and the signal intensity of succinic acid and 3-mercaptolactic acid were observed. These results highlight the need to educate the participants about the intake level of the nutrients involved in iAs metabolism and may contribute to further considerations with respect to the formulation of dietary recommendations for people exposed to iAs.PMID:36676995 | DOI:10.3390/metabo13010070

Metabolites. 2023 Jan 1;13(1):68. doi: 10.3390/metabo13010068.ABSTRACTShaziling pigs, as a native Chinese breed, have been classified as a fatty liver model. As the core of the whole pig farm, the sow's organism health is especially important, especially in the perinatal period; however, there are few reports on the perinatal intestinal microbiology and bile acid metabolism of Shaziling pig sows. The purpose of this research was to investigate the alterations in bile acids and gut microbiota of sows that occur throughout the perinatal period. Forty-two sows were selected for their uniformity of body conditions and were given the same diet. Fecal samples were collected for 16srDNA sequencing and bile acid targeted metabolome detection in four stages (3 days before delivery, 3 days after delivery, 7 days after delivery and 21 days after delivery). As revealed by the results, there were statistically significant variations in bile acids among the four stages, with the concentration of bile acids identified by SZL-4 being substantially greater than that of the other three groups (p < 0.05). When compared to the other three groups (p < 0.05), SZL-2 had considerably lower Shannon, Simpson and Chao 1 indices, and exhibited a statistically significant difference in β-diversity. SZL-2 samples included a greater proportion of Proteobacteria than SZL-3 and SZL-4 samples; however, SZL-2 samples contained a smaller proportion of spirochetes than SZL-3 and SZL-4 samples. To a large extent, lactic acid bacteria predominated in the SZL-2 samples. The LEfSe analysis showed that the relative abundances of Lachnospiraceae_XPB1014_group, Christensenellaceae_R_7_group, Clostridium, Collinsella, Turicibacter, and Mollicutes_RF39_unclassified were the main differential bacteria in the SZL-1 swine fecal samples and the Eubacterium__coprostanoligenes_group in sow fecal samples from SZL-2. The relative abundance of Bacteroides, UBA1819, Enterococcus, Erysipelatoclostridium, and Butyricimonas in SZL-3 and SZL-4 Streptococcus, Coriobacteriaceae_unclassified, Prevotellaceae_UCG_001, Streptomyces, and Ochrobactrum in SZL-3. g_Collinsella was significantly and positively correlated with vast majority bile acids, and the g_Lachnospiraceae_XPB1014_group with GCDCA and GHDCA into positive correlations. Simultaneously, g_Streptococcus, g_Bacteroides, and g_UBA1819 inversely correlated with bile acid, accounting for the great bulk of the difference. In conclusion, there is an evident correlation between bile acids and gut microbiota in the perinatal period of Shaziling sows. Additionally, the discovery of distinct bacteria associated to lipid metabolism gives a reference for ameliorating perinatal body lipid metabolism disorder of sows through gut microbiota.PMID:36676993 | DOI:10.3390/metabo13010068

Metabolites. 2023 Jan 1;13(1):67. doi: 10.3390/metabo13010067.ABSTRACTMetabolomics is one of the most promising 'omics' sciences for the implementation in medicine by developing new diagnostic tests and optimizing drug therapy. Since in metabolomics, the end products of the biochemical processes in an organism are studied, which are under the influence of both genetic and environmental factors, the metabolomics analysis can detect any changes associated with both lifestyle and pathological processes. Almost every case-controlled metabolomics study shows a high diagnostic accuracy. Taking into account that metabolomics processes are already described for most nosologies, there are prerequisites that a high-speed and comprehensive metabolite analysis will replace, in near future, the narrow range of chemical analyses used today, by the medical community. However, despite the promising perspectives of personalized metabolomics, there are currently no FDA-approved metabolomics tests. The well-known problem of complexity of personalized metabolomics data analysis and their interpretation for the end-users, in addition to a traditional need for analytical methods to address the quality control, standardization, and data treatment are reported in the review. Possible ways to solve the problems and change the situation with the introduction of metabolomics tests into clinical practice, are also discussed.PMID:36676992 | DOI:10.3390/metabo13010067

Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2217543120. doi: 10.1073/pnas.2217543120. Epub 2023 Jan 20.ABSTRACTNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, in which prognosis is determined by liver fibrosis. A common variant in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13, rs72613567-A) is associated with a reduced risk of fibrosis in NAFLD, but the underlying mechanism(s) remains unclear. We investigated the effects of this variant in the human liver and in Hsd17b13 knockdown in mice by using a state-of-the-art metabolomics approach. We demonstrate that protection against liver fibrosis conferred by the HSD17B13 rs72613567-A variant in humans and by the Hsd17b13 knockdown in mice is associated with decreased pyrimidine catabolism at the level of dihydropyrimidine dehydrogenase. Furthermore, we show that hepatic pyrimidines are depleted in two distinct mouse models of NAFLD and that inhibition of pyrimidine catabolism by gimeracil phenocopies the HSD17B13-induced protection against liver fibrosis. Our data suggest pyrimidine catabolism as a therapeutic target against the development of liver fibrosis in NAFLD.PMID:36669104 | DOI:10.1073/pnas.2217543120

Toxins (Basel). 2023 Jan 6;15(1):48. doi: 10.3390/toxins15010048.ABSTRACTThe estrogenic mycotoxin zearalenone (ZEN) is a common contaminant of animal feed. Effective strategies for the inactivation of ZEN in feed are required. The ZEN-degrading enzyme zearalenone hydrolase ZenA (EC 3.1.1.-, commercial name ZENzyme®, BIOMIN Holding GmbH, Getzersdorf, Austria) converts ZEN to hydrolyzed ZEN (HZEN), thereby enabling a strong reduction in estrogenicity. In this study, we investigated the efficacy of ZenA added to feed to degrade ZEN in the gastrointestinal tract of three monogastric animal species, i.e., pigs, chickens, and rainbow trout. For each species, groups of animals received (i) feed contaminated with ZEN (chickens: 400 µg/kg, pigs: 200 µg/kg, rainbow trout: 2000 µg/kg), (ii) feed contaminated with ZEN and supplemented with ZenA, or (iii) uncontaminated feed. To investigate the fate of dietary ZEN in the gastrointestinal tract in the presence and absence of ZenA, concentrations of ZEN and ZEN metabolites were analyzed in digesta of chickens and rainbow trout and in feces of pigs. Upon ZenA administration, concentrations of ZEN were significantly decreased and concentrations of the degradation product HZEN were significantly increased in digesta/feces of each investigated animal species, indicating degradation of ZEN by ZenA in the gastrointestinal tract. Moreover, upon addition of ZenA to the diet, the concentration of the highly estrogenic ZEN metabolite α-ZEL was significantly reduced in feces of pigs. In conclusion, ZenA was effective in degrading ZEN to HZEN in the gastrointestinal tract of chickens, pigs, and rainbow trout, and counteracted formation of α-ZEL in pigs. Therefore, ZenA could find application as a ZEN-degrading feed additive for these animal species.PMID:36668868 | DOI:10.3390/toxins15010048

Toxics. 2022 Dec 31;11(1):44. doi: 10.3390/toxics11010044.ABSTRACTOBJECTIVE: To find the metabolomic characteristics of tumor or para-tumor tissues, and the differences in serums from papillary thyroid cancer (PTC) patients with or without lymph node metastasis.METHODS: We collected serums of PTC patients with/without lymph node metastasis (SN1/SN0), tumor and adjacent tumor tissues of PTC patients with lymph node metastasis (TN1 and PN1), and without lymph node metastasis (TN0 and PN0). Metabolite detection was performed by ultra-high performance liquid chromatography combined with Q-Exactive orbitrap mass spectrometry (UPLC Q-Exactive).RESULTS: There were 31, 15, differential metabolites in the comparisons of TN1 and PN1, TN0 and PN0, respectively. Seven uniquely increased metabolites and fourteen uniquely decreased metabolites appeared in the lymph node metastasis (TN1 and PN1) group. Meanwhile, the results indicated that four pathways were co-owned pathways in two comparisons (TN1 and PN1, TN0 and PN0), and four unique pathways presented in the lymph node metastasis (TN1 and PN1) group.CONCLUSIONS: Common or differential metabolites and metabolic pathways were detected in the lymph node metastasis and non-metastatic group, which might provide novel ways for the diagnosis and treatment of PTC.PMID:36668770 | DOI:10.3390/toxics11010044

Mar Drugs. 2023 Jan 14;21(1):53. doi: 10.3390/md21010053.ABSTRACTSponges are the richest source of bioactive organic small molecules, referred to as natural products, in the marine environment. It is well established that laboratory culturing-resistant symbiotic bacteria residing within the eukaryotic sponge host matrix often synthesize the natural products that are detected in the sponge tissue extracts. However, the contributions of the culturing-amenable commensal bacteria that are also associated with the sponge host to the overall metabolome of the sponge holobiont are not well defined. In this study, we cultured a large library of bacteria from three marine sponges commonly found in the Florida Keys. Metabolomes of isolated bacterial strains and that of the sponge holobiont were compared using mass spectrometry to reveal minimal metabolomic overlap between commensal bacteria and the sponge hosts. We also find that the phylogenetic overlap between cultured commensal bacteria and that of the sponge microbiome is minimal. Despite these observations, the commensal bacteria were found to be a rich resource for novel natural product discovery. Mass spectrometry-based metabolomics provided structural insights into these cryptic natural products. Pedagogic innovation in the form of laboratory curricula development is described which provided undergraduate students with hands-on instruction in microbiology and natural product discovery using metabolomic data mining strategies.PMID:36662226 | DOI:10.3390/md21010053

Mar Drugs. 2023 Jan 12;21(1):50. doi: 10.3390/md21010050.ABSTRACTThe search for new antibiotics against drug-resistant microbes has been expanded to marine bacteria. Marine bacteria have been proven to be a prolific source of a myriad of novel compounds with potential biological activities. Therefore, this review highlights novel and bioactive compounds from marine bacteria reported during the period of January 2016 to December 2021. Published articles containing novel marine bacterial secondary metabolites that are active against drug-resistant pathogens were collected. Previously described compounds (prior to January 2016) are not included in this review. Unreported compounds during this period that exhibited activity against pathogenic microbes were discussed and compared in order to find the cue of the structure-bioactivity relationship. The results showed that Streptomyces are the most studied bacteria with undescribed bioactive compounds, followed by other genera in the Actinobacteria. We have categorized the structures of the compounds in the present review into four groups, based on their biosynthetic origins, as polyketide derivatives, amino acid derivatives, terpenoids, as well as compounds with mixed origin. These compounds were active against one or more drug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant Enterococci (VRE), multidrug-resistant Mycobacterium tuberculosis (MDR-TB), and amphotericin B-resistant Candida albicans. In addition, some of the compounds also showed activity against biofilm formation of the test bacteria. Some previously undescribed compounds, isolated from marine-derived bacteria during this period, could have a good potential as lead compounds for the development of drug candidates to overcome multidrug-resistant pathogens.PMID:36662223 | DOI:10.3390/md21010050

Insects. 2023 Jan 10;14(1):68. doi: 10.3390/insects14010068.ABSTRACTPopulation-density-dependent polymorphism is important in the biology of some agricultural pests. The oriental armyworm (Mythimna separata) is a lepidopteran pest (family Noctuidae). As the population density increases, its body color becomes darker, and the insect eats more and causes greater damage to crops. The molecular mechanisms underlying this phase change are not fully clear. Here, we used transcriptomic and metabolomic methods to study the effect of population density on the differentiation of second-day sixth instar M. separata larvae. The transcriptomic analysis identified 1148 differentially expressed genes (DEGs) in gregarious-type (i.e., high-population-density) armyworms compared with solitary-type (low-population-density) armyworms; 481 and 667 genes were up- and downregulated, respectively. The metabolomic analysis identified 137 differentially accumulated metabolites (DAMs), including 59 upregulated and 78 downregulated. The analysis of DEGs and DAMs showed that activation of the insulin-like signaling pathway promotes the melanization of gregarious armyworms and accelerates the decomposition of saccharides, which promotes the gregarious type to take in more food. The gregarious type is more capable of digesting and absorbing proteins and decreases energy consumption by inhibiting transcription and translation processes. The phase change traits of the armyworm are thus attributable to plasticity of its energy metabolism. These data broaden our understanding of the molecular mechanisms of insect-density-dependent polymorphism.PMID:36661996 | DOI:10.3390/insects14010068

Insects. 2022 Dec 30;14(1):37. doi: 10.3390/insects14010037.ABSTRACTPollen is essential to the development of honey bees. The nutrients in bee pollen vary greatly among plant species. Here, we analyzed the differences in the amino acid compositions of pear (Pyrus bretschneideri), rape (Brassica napus), and apricot (Armeniaca sibirica) pollens and investigated the variation in hemolymph metabolites and metabolic pathways through untargeted metabolomics in caged adult bees at days 7 and 14. The results showed that the levels of five essential amino acids (isoleucine, phenylalanine, lysine, methionine, and histidine) were the highest in pear pollen, and the levels of four amino acids (isoleucine: 50.75 ± 1.93 mg/kg, phenylalanine: 87.25 ± 2.66 mg/kg, methionine: 16.00 ± 0.71 mg/kg and histidine: 647.50 ± 24.80 mg/kg) were significantly higher in pear pollen than in the other two kinds of bee pollen (p < 0.05). The number of metabolites in bee hemolymph on day 14 (615) was significantly lower than that on day 7 (1466). The key metabolic pathways of bees, namely, "sphingolipid metabolism (p = 0.0091)", "tryptophan metabolism (p = 0.0245)", and "cysteine and methionine metabolism (p = 0.0277)", were significantly affected on day 7. There was no meaningful pathway enrichment on day 14. In conclusion, pear pollen had higher nutritional value among the three bee pollens in terms of amino acid level, followed by rape and apricot pollen, and the difference in amino acid composition among bee pollens was reflected in the lipid and amino acid metabolism pathways of early adult honey bee hemolymph. This study provides new insights into the physiological and metabolic functions of different bee pollens in bees.PMID:36661964 | DOI:10.3390/insects14010037

Inflamm Bowel Dis. 2023 Jan 20:izac268. doi: 10.1093/ibd/izac268. Online ahead of print.ABSTRACTBACKGROUND: Intestinal Immunoglobulin A (IgA) is crucial in maintaining host-microbiota mutualism and gut homeostasis. It has been shown that many species of gut bacteria produce cyclic dinucleotides, along with an abundance of microbiota-derived DNA present within the intestinal lumen, which triggers the tonic activation of the cytosolic cGAS-STING pathway. However, the role of STING in intestinal IgA remains poorly understood. We further investigated whether and how STING affects intestinal IgA response.METHODS: Intestinal IgA was determined between wild-type (WT) mice and Sting-/- mice in steady conditions and upon enteric Citrobacter rodentium infection. STING agonists were used to stimulating B cells or dendritic cells in vitro. Gut microbiota composition was examined by 16S ribosomal RNA gene sequencing. Bacteria metabolomics functional analyses was performed by PICRUSt2. Fecal short-chain fatty acid (SCFA) was determined by Mass spectrometry and Cedex Bio Analyzer. Gut bacteria from WT mice and Sting-/- mice were transferred into germ-free mice and antibiotic-pretreated mice.RESULTS: Intestinal IgA response was impaired in Sting-/- mice. However, STING agonists did not directly stimulate B cells or dendritic cells to induce IgA. Interestingly, Sting-/- mice displayed altered gut microbiota composition with decreased SCFA-producing bacteria and downregulated SCFA fermentation pathways. Transfer of fecal bacteria from Sting-/- mice induced less IgA than that from WT mice in germ-free mice and antibiotic-pretreated mice, which is mediated by GPR43. Acetate, the dominant SCFA, was decreased in Sting-/- mice, and supplementation of acetate restored intestinal IgA production in Sting-/- mice.CONCLUSIONS: STING promotes intestinal IgA by regulating acetate-producing gut bacteria.PMID:36661414 | DOI:10.1093/ibd/izac268

Redox Rep. 2023 Dec;28(1):2163354. doi: 10.1080/13510002.2022.2163354.ABSTRACTObjective: Adrenocortical responsiveness is critical for maintaining glucocorticoids production and homeostasis during stress. We sought to investigate adrenocortical responsiveness during hypoxia in mice and the mechanisms responsible for the regulation of adrenal responsiveness.Methods: (1) Adult male WT mice were randomly divided into four groups: normoxia, hypoxia (24h), hypoxia (72h), hypoxia (72h) + GYY4137(hydrogen sulfide (H2S) donor, 133mmol/kg/day); (2) WT mice were randomly divided into four groups: sham, adrenalectomy (ADX), sham+hypoxia, ADX+hypoxia; (3) Cse-/- mice were randomly divided into two groups: Cse-/-, Cse-/- +GYY4137.Results: The circulatory level of corticosteroid induced by ACTH stimulation was significantly reduced in the mice with hypoxia compared with control mice. The mortality rate induced by lipopolysaccharide (LPS) increased during hypoxia. Cystathionine-γ-lyase (CSE) expression was significantly reduced in adrenal glands during hypoxia. GYY4137 treatment significantly increased adrenal responsiveness and attenuated NLRP3 inflammasome activation in mice treated by hypoxia and Cse-/- mice. Furthermore, The sulfhydrated level of PSMA7 in adrenal gland was decreased in the mice with hypoxia and Cse-/- mice. PSMA7 was S-sulfhydrated at cysteine 70. Blockage of S-sulfhydration of PSMA7 increased NLRP3 expression in adrenocortical cells.Conclusion: Reduced H2S production mediated hypo-adrenocortical responsiveness and NLRP3 inflammasome activation via PAMA7 S-sulfhydration during hypoxia.PMID:36661247 | DOI:10.1080/13510002.2022.2163354

Ann Transl Med. 2022 Dec;10(24):1330. doi: 10.21037/atm-22-5614.ABSTRACTBACKGROUND: Although metabolic abnormalities have been deemed one of the essential risk factors for growth and development, the relationship between metabolic abnormalities and microtia is still unclear. In this study, we aimed to establish a cell model of microtia and the changes of serum metabolites in patients with microtia.METHODS: After constructing a cell model of microtia with low expression of BMP5, we performed integrative metabolomics analysis. For the altered metabolites, the content of glycerophosphocholine (PC), triacylglycerol (TG), and choline in the serum of 28 patients (15 patients with microtia and 13 controls) with microtia was verified by enzyme-linked immunosorbent assay (ELISA).RESULTS: Detailed metabolomic evaluation showed distinct clusters of metabolites between BMP5-low expressing cells and normal control (NC) cells. The cell model of microtia had significantly higher levels of TG, PC, glycerophosphoethanolamine (PE), sphingomyelin, sulfatide, glycerophosphoglycerol, diacylglycerol, and glycosphingolipid. The main abnormal metabolites were mainly concentrated in the glycerophospholipid metabolism pathway, and PC and choline were closely related. In the serum of patients with microtia, the contents of PC, TG, and choline were significantly increased.CONCLUSIONS: The individual serum samples confirmed the different metabolites between patients with microtia and controls. In particular, we showed that a newly developed metabolic biomarker panel has a high sensitivity and specificity for separating patients with microtia from controls.PMID:36660691 | PMC:PMC9843322 | DOI:10.21037/atm-22-5614

Cell Mol Bioeng. 2022 Nov 27;16(1):41-54. doi: 10.1007/s12195-022-00749-5. eCollection 2023 Feb.ABSTRACTINTRODUCTION: Syringomyelia (SM) is a debilitating spinal cord disorder in which a cyst, or syrinx, forms in the spinal cord parenchyma due to congenital and acquired causes. Over time syrinxes expand and elongate, which leads to compressing the neural tissues and a mild to severe range of symptoms. In prior omics studies, significant upregulation of betaine and its synthesis enzyme choline dehydrogenase (CHDH) were reported during syrinx formation/expansion in SM injured spinal cords, but the role of betaine regulation in SM etiology remains unclear. Considering betaine's known osmoprotectant role in biological systems, along with antioxidant and methyl donor activities, this study aimed to better understand osmotic contributions of synthesized betaine by CHDH in response to SM injuries in the spinal cord.METHODS: A post-traumatic SM (PTSM) rat model and in vitro cellular models using rat astrocytes and HepG2 liver cells were utilized to investigate the role of betaine synthesis by CHDH. Additionally, the osmotic contributions of betaine were evaluated using a combination of experimental as well as simulation approaches.RESULTS: In the PTSM injured spinal cord CHDH expression was observed in cells surrounding syrinxes. We next found that rat astrocytes and HepG2 cells were capable of synthesizing betaine via CHDH under osmotic stress in vitro to maintain osmoregulation. Finally, our experimental and simulation approaches showed that betaine was capable of directly increasing meaningful osmotic pressure.CONCLUSIONS: The findings from this study demonstrate new evidence that CHDH activity in the spinal cord provides locally synthesized betaine for osmoregulation in SM pathophysiology.SUPPLEMENTARY INFORMATION: The online version of this article contains supplementary material available 10.1007/s12195-022-00749-5.PMID:36660584 | PMC:PMC9842837 | DOI:10.1007/s12195-022-00749-5

J Clin Endocrinol Metab. 2023 Jan 20:dgad032. doi: 10.1210/clinem/dgad032. Online ahead of print.ABSTRACTCONTEXT: Ageing varies between individuals with profound consequences for chronic diseases and longevity. One hypothesis to explain the diversity is a genetically regulated molecular clock that runs differently between individuals. Large and long enough human studies to test the hypothesis are rare due to practical challenges, but statistical models of ageing are built as proxies for the molecular clock by comparing young and old individuals cross-sectionally. These models remain untested against longitudinal data.OBJECTIVE: We applied novel methodology to test if cross-sectional modelling can distinguish slow versus accelerated ageing in a human population.DESIGN: We trained a machine learning model to predict age from 153 clinical and cardiometabolic traits. The model was tested against longitudinal data from another cohort.PATIENTS OR OTHER PARTICIPANTS: The training data came from cross-sectional surveys of the Finnish population (n = 9,708; ages 25-74 years). The validation data included three time points across 10 years in the Young Finns Study (YFS; n = 1,009; ages 24-49 years).INTERVENTION(S): Predicted metabolic age in 2007 was compared against observed ageing rate from the 2001 visit to the 2011 visit in the YFS dataset.MAIN OUTCOME MEASURE(S): Correlation between predicted versus observed metabolic ageing.RESULTS: The cross-sectional proxy failed to predict longitudinal observations (R2 = 0.018%, P = 0.67).CONCLUSIONS: The finding is unexpected under the clock hypothesis that would produce a positive correlation between predicted and observed ageing. Our results are better explained by a stratified model where ageing rates per se are similar in adulthood but differences in starting points explain diverging metabolic fates.PMID:36658689 | DOI:10.1210/clinem/dgad032

PeerJ. 2023 Jan 13;11:e14563. doi: 10.7717/peerj.14563. eCollection 2023.ABSTRACTOsteoarthritis (OA) is the most common joint disease in the world, characterized by pain and loss of joint function, which has led to a serious reduction in the quality of patients' lives. In this work, ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QToF/MS) in conjunction with multivariate pattern recognition methods and an univariate statistical analysis scheme were applied to explore the serum metabolic signatures within OA group (n = 31), HC (healthy controls) group (n = 57) and non-OA group (n = 19) for early diagnosis and differential diagnosis of OA. Based on logistic regression analysis and receiver operating characteristic (ROC) curve analysis, seven metabolites, including phosphatidylcholine (18:0/22:6), p-cresol sulfate and so on, were identified as critical metabolites for the diagnosis of OA and HC and yielded an area under the curve (AUC) of 0.978. The other panel of unknown m/z 239.091, phosphatidylcholine (18:0/18:0) and phenylalanine were found to distinguish OA from non-OA and achieved an AUC of 0.888. These potential biomarkers are mainly involved in lipid metabolism, glucose metabolism and amino acid metabolism. It is expected to reveal new insight into OA pathogenesis from changed metabolic pathways.PMID:36655043 | PMC:PMC9841907 | DOI:10.7717/peerj.14563

Skelet Muscle. 2023 Jan 19;13(1):2. doi: 10.1186/s13395-022-00312-w.ABSTRACTBACKGROUND: Sarcopenia is one of the most predominant musculoskeletal diseases of the elderly, defined as age-related progressive and generalized loss of muscle mass with a simultaneous reduction in muscle strength and/or function. Using metabolomics, we aimed to examine the association between sarcopenia and the plasma metabolic profile of sarcopenic patients, measured using a targeted HPLC-MS/MS platform.METHODS: Plasma samples from 22 (17 men) hip fracture patients undergoing surgery (8 sarcopenic, age 81.4+6.3, and 14 non-sarcopenic, age 78.4±8.1) were analyzed. T test, fold change, orthogonal partial least squares discriminant analysis, and sparse partial least squares discriminant analysis were used for mining significant features. Metabolite set enrichment analysis and mediation analysis by PLSSEM were thereafter performed.RESULTS: Using a univariate analysis for sarcopenia z score, the amino acid citrulline was the only metabolite with a significant group difference after FDR correction. Positive trends were observed between the sarcopenia z score and very long-chain fatty acids as well as dicarboxylic acid carnitines. Multivariate analysis showed citrulline, non-esterified fatty acid 26:2, and decanedioyl carnitine as the top three metabolites according to the variable importance in projection using oPLS-DA and loadings weight by sPLS-DA. Metabolite set enrichment analysis showed carnitine palmitoyltransferase deficiency (II) as the highest condition related to the metabolome.CONCLUSIONS: We observed a difference in the plasma metabolic profile in association with different measures of sarcopenia, which identifies very long-chain fatty acids, Carn.DC and citrulline as key variables associated with the disease severity. These findings point to a potential link between sarcopenia and mitochondrial dysfunction and portraits a number of possible biochemical pathways which might be involved in the disease pathogenesis.PMID:36658632 | DOI:10.1186/s13395-022-00312-w

BMC Oral Health. 2023 Jan 19;23(1):30. doi: 10.1186/s12903-023-02722-8.ABSTRACTBACKGROUND: Severe early childhood caries (SECC) is an inflammatory disease with complex pathology. Although changes in the oral microbiota and metabolic profile of patients with SECC have been identified, the salivary metabolites and the relationship between oral bacteria and biochemical metabolism remains unclear. We aimed to analyse alterations in the salivary microbiome and metabolome of children with SECC as well as their correlations. Accordingly, we aimed to explore potential salivary biomarkers in order to gain further insight into the pathophysiology of dental caries.METHODS: We collected 120 saliva samples from 30 children with SECC and 30 children without caries. The microbial community was identified through 16S ribosomal RNA (rRNA) gene high-throughput sequencing. Additionally, we conducted non-targeted metabolomic analysis through ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry to determine the relative metabolite levels and their correlation with the clinical caries status.RESULTS: There was a significant between-group difference in 8 phyla and 32 genera in the microbiome. Further, metabolomic and enrichment analyses revealed significantly altered 32 salivary metabolites in children with dental caries, which involved pathways such as amino acid metabolism, pyrimidine metabolism, purine metabolism, ATP-binding cassette transporters, and cyclic adenosine monophosphate signalling pathway. Moreover, four in vivo differential metabolites (2-benzylmalate, epinephrine, 2-formaminobenzoylacetate, and 3-Indoleacrylic acid) might be jointly applied as biomarkers (area under the curve = 0.734). Furthermore, the caries status was correlated with microorganisms and metabolites. Additionally, Spearman's correlation analysis of differential microorganisms and metabolites revealed that Veillonella, Staphylococcus, Neisseria, and Porphyromonas were closely associated with differential metabolites.CONCLUSION: This study identified different microbial communities and metabolic profiles in saliva, which may be closely related to caries status. Our findings could inform future strategies for personalized caries prevention, detection, and treatment.PMID:36658579 | DOI:10.1186/s12903-023-02722-8