PubMed

Front Mol Biosci. 2022 Dec 12;9:1101980. doi: 10.3389/fmolb.2022.1101980. eCollection 2022.ABSTRACT[This corrects the article DOI: 10.3389/fmolb.2022.931946.].PMID:36579186 | PMC:PMC9791986 | DOI:10.3389/fmolb.2022.1101980

iScience. 2022 Dec 5;26(1):105725. doi: 10.1016/j.isci.2022.105725. eCollection 2023 Jan 20.ABSTRACTThe emergence and spread of artemisinin-tolerant malaria parasites threatens malaria control programmes worldwide. Mutations in the propeller domain of the Kelch13 protein confer Plasmodium falciparum artemisinin resistance (ART-R). ART-R is linked to the reduced susceptibility of temporary growth-arrested ring-stage parasites, but the metabolic mechanisms remain elusive. We generated two PfKelch13 mutant lines via CRISPR-Cas9 gene editing which displayed a reduced susceptibility accompanied by an extended ring stage. The metabolome of ART-induced ring-stage growth arrest parasites carrying PfKelch13 mutations showed significant alterations in the tricarboxylic acid (TCA) cycle, glycolysis, and amino acids metabolism, pointing to altered energy and porphyrin metabolism with metabolic plasticity. The critical role of these pathways was further confirmed by altering metabolic flow or through chemical inhibition. Our findings uncover that the growth arrestment associated with ART-R is potentially attributed to the adaptative metabolic plasticity, indicating that the defined metabolic remodeling turns out to be the trigger for ART-R.PMID:36579133 | PMC:PMC9791339 | DOI:10.1016/j.isci.2022.105725

Noro Psikiyatr Ars. 2022 Dec 16;59(Suppl 1):S36-S41. doi: 10.29399/npa.28169. eCollection 2022.ABSTRACTParkinson's disease (PD) is a neurodegenerative disease with a rapidly increasing incidence and prevalence. Although it affects more than 6 million people worldwide, it is predicted to be doubled by 2040. Current criteria used in the diagnosis of PD include the presence of bradykinesia as well as the presence of rest tremor and/or rigidity, but the clinic is multifaceted and includes many non-motor symptoms. Non-motor symptoms may occur in the prodromal period, years before clinically evident Parkinson's disease. During this period, diagnosing the disease will likely be even more important when disease-modifying treatments are available. Currently, there is no single biomarker that can be used in the diagnosis of PD and no disease-modifying treatment is available. Identification of biomarkers in early diagnosis will enable the most effective use of disease-modifying therapies and will shed light on possible underlying pathologies, studies in this area have gained momentum in recent years. Molecular imaging methods, genetic studies, salivary gland and skin biopsies, metabolomics, lysosomal pathway are some of them. In this article, besides the current diagnosis and treatment methods of the disease, biomarkers and treatments that are expected to be better understood in the near future will be mentioned.PMID:36578989 | PMC:PMC9767134 | DOI:10.29399/npa.28169

Front Cardiovasc Med. 2022 Dec 12;9:1009165. doi: 10.3389/fcvm.2022.1009165. eCollection 2022.ABSTRACTOBJECTIVE: Fetal cardiopulmonary bypass (CPB) is essential to fetal heart surgery, while its development is limited by vital organ dysfunction after CPB. Studying organ metabolism may help to solve this problem. The objective of this study was to describe the tissue-specific metabolic fingerprints of fetal sheep under CPB and to associate them with organ functions.METHODS: Ten pregnant ewes at 90-120 days of gestation were randomly divided into two groups. The bypass group underwent a 1-h fetal CPB, whereas the control group underwent only a fetal sternotomy. During bypass, echocardiography, blood gases, and blood biochemistry were measured. After bypass, lambs were sacrificed, and tissues of the heart, liver, brain, kidney, and placenta were harvested. The metabolites extracted from these tissues were analyzed using non-targeted metabolomics based on liquid chromatography-mass spectrometry techniques.RESULTS: All tissues except the placenta displayed significant metabolic changes, and the fetal heart displayed obvious functional changes. Fetal sheep that underwent CPB had common and tissue-specific metabolic signatures. These changes can be attributed to dysregulated lipid metabolism, altered amino acid metabolism, and the accumulation of plasticizer metabolism.CONCLUSION: Fetal CPB causes tissue-specific metabolic changes in fetal sheep. Studying these metabolic changes, especially cardiac metabolism, is of great significance for the study of fetal CPB.PMID:36578834 | PMC:PMC9791045 | DOI:10.3389/fcvm.2022.1009165

Front Pediatr. 2022 Dec 12;10:1063248. doi: 10.3389/fped.2022.1063248. eCollection 2022.ABSTRACTAccurate prediction of preterm birth is currently challenging, resulting in unnecessary maternal hospital admittance and fetal overexposure to antenatal corticosteroids. Novel biomarkers like volatile organic compounds (VOCs) hold potential for predictive, bed-side clinical applicability. In a proof of principle study, we aimed to assess the predictive potential of urinary volatile organic compounds in the identification of pregnant women at risk for preterm birth. Urine samples of women with a high risk for preterm birth (≧24 + 0 until 36 + 6 weeks) were collected prospectively and analyzed for VOCs using gas chromatography coupled with an ion mobility spectrometer (GS-IMS). Urinary VOCs of women delivering preterm were compared with urine samples of women with suspicion of preterm birth collected at the same gestation period but delivering at term. Additionally, the results were also interpreted in combination with patient characteristics, such as physical examination at admission, microbial cultures, and placental pathology. In our cohort, we found that urinary VOCs of women admitted for imminent preterm birth were not significantly different in the overall group of women delivering preterm vs. term. However, urinary VOCs of women admitted for imminent preterm birth and delivering between 28 + 0 until 36 + 6 weeks compared to women with a high risk for preterm birth during the same gestation period and eventually delivering at term (>37 + 0 weeks) differed significantly (area under the curve: 0.70). In addition, based on the same urinary VOCs, we could identify women with a confirmed chorioamnionitis (area under the curve: 0.72) and urinary tract infection (area under the curve: 0.97). In conclusion, urinary VOCs hold potential for non-invasive, bedside prediction of preterm birth and on the spot identification of intra-uterine infection and urinary tract infections. We suggest these observations are further explored in larger populations.PMID:36578660 | PMC:PMC9791099 | DOI:10.3389/fped.2022.1063248

Front Microbiol. 2022 Dec 12;13:1032870. doi: 10.3389/fmicb.2022.1032870. eCollection 2022.ABSTRACTINTRODUCTION: To develop functional foods with traditional medicines and homologous food ingredients as well as human milk-derived probiotics, the co-fermentation process of two probiotics, Lactobacillus plantarum R9 and Lactobacillus gasseri B1-27, isolated from the human milk of healthy parturients and the traditional medicine and food homologous ingredient Poria cocos, were separately investigated.RESULTS: The Poria cocos fermentation broth at 2.5% significantly enhanced the total number of L. plantarum R9 (p = 0.001) and L. gasseri B1-27 (p = 0.013) after 20 h of fermentation, and Non-targeted metabolomics assays conducted before and after fermentation of the human milk-derived L. plantarum R9 and L. gasseri B1-27 using the 2.5% Poria cocos fermentation broth revealed 35 and 45 differential metabolites, respectively. A variety of active substances with physiological functions, such as L-proline, L-serine, beta-alanine, taurine, retinol, luteolin, and serotonin, were found to be significantly increased. Mannitol, a natural sweetener with a low glycemic index, was also identified. The most significantly altered metabolic pathways were pyrimidine metabolism, pentose phosphate, yeast meiosis, ABC transporter, insulin signaling, and mineral absorption, suggesting that co-fermentation of human milk-derived probiotics and Poria cocos may affect the metabolism of trace minerals, sugars, organic acids, and amino acids.DISCUSSION: Overall, we determined that the optimal concentration of Poria cocos to be used in co-fermentation was 2.5% and identified more than 35 differentially expressed metabolites in each probiotic bacteria after co-fermentation. Moreover, several beneficial metabolites were significantly elevated as a result of the co-fermentation process indicating the valuable role of Poria cocos as a functional food.PMID:36578582 | PMC:PMC9791117 | DOI:10.3389/fmicb.2022.1032870

Front Microbiol. 2022 Dec 12;13:1100290. doi: 10.3389/fmicb.2022.1100290. eCollection 2022.ABSTRACT[This corrects the article DOI: 10.3389/fmicb.2022.965709.].PMID:36578573 | PMC:PMC9791648 | DOI:10.3389/fmicb.2022.1100290

Extracell Vesicle. 2022 Dec;1:100004. doi: 10.1016/j.vesic.2022.100004. Epub 2022 Jul 1.ABSTRACTExtracellular vesicles (EV) as drug delivery nanocarriers are under intense investigation. Although clinical-grade EVs have been produced on a large-scale, low yield and high production costs of natural EVs (nEV) limit the relevant industrial translation. Recent studies show that mechanical extrusion of cells can generate nEV-like cell-derived nanovesicles (CNV) which can also be used as drug nanocarriers. Moreover, in comparison with nEVs, CNVs have similar physicochemical properties. Nevertheless, a comprehensive comparison of cargo between nEVs and CNVs has not been investigated yet. Therefore, the aim of this study is to profile and compare CNVs to nEVs. Our results show that no significant difference was found in size, morphology, and classical markers between nEVs and CNVs derived from MDA-MB-231 cells. Protein sequencing data reveals the similarity of membrane proteins between the two groups was ~71%, while it was ~21% when pertaining to total protein cargo. Notably, a high similarity of membrane proteins was also found between nEVs and CNVs derived from eight additional cancer cell lines. Moreover, analysis of the top 1000 small RNAs with RNA sequencing showed a ~65% similarity between the two groups. Altogether, we infer from the high similarity of membrane proteins and small RNA cargo that CNVs can be a good substitute for nEVs. In brief, our findings support previous studies with a notion that CNVs yield comparable performance with nEVs and could pave the way for clinical implementation of CNV-based therapeutics in the future.PMID:36578271 | PMC:PMC9794200 | DOI:10.1016/j.vesic.2022.100004

Sci Rep. 2022 Dec 28;12(1):22473. doi: 10.1038/s41598-022-26551-x.ABSTRACTPlants deposit photosynthetically-fixed carbon in the rhizosphere, the thin soil layer directly around the root, thereby creating a hospitable environment for microbes. To manage the inhabitants of this nutrient-rich environment, plant roots exude and dynamically adjust microbe-attracting and -repelling compounds to stimulate specific members of the microbiome. Previously, we demonstrated that foliar infection of Arabidopsis thaliana by the biotrophic downy mildew pathogen Hyaloperonospora arabidopsidis (Hpa) leads to a disease-induced modification of the rhizosphere microbiome. Soil conditioned with Hpa-infected plants provided enhanced protection against foliar downy mildew infection in a subsequent population of plants, a phenomenon dubbed the soil-borne legacy (SBL). Here, we show that for the creation of the SBL, plant-produced coumarins play a prominent role as coumarin-deficient myb72 and f6'h1 mutants were defective in creating a Hpa-induced SBL. Root exudation profiles changed significantly in Col-0 upon foliar Hpa infection, and this was accompanied by a compositional shift in the root microbiome that was significantly different from microbial shifts occurring on roots of Hpa-infected coumarin-deficient mutants. Our data further show that the Hpa-induced SBL primes Col-0 plants growing in SBL-conditioned soil for salicylic acid (SA)-dependent defenses. The SA-signaling mutants sid2 and npr1 were unresponsive to the Hpa-induced SBL, suggesting that the protective effect of the Hpa-induced shift in the root microbiome results from an induced systemic resistance that requires SA-signaling in the plant.PMID:36577764 | DOI:10.1038/s41598-022-26551-x

NPJ Sci Food. 2022 Dec 28;6(1):60. doi: 10.1038/s41538-022-00174-y.ABSTRACTColorectal cancer (CRC) is the second most prevelant malignancy in Europe and diet is an important modifiable risk factor. Processed meat consumption, including meats with preservative salts such as sodium nitrite, have been implicated in CRC pathogenesis. This study investigated how the CRC pathology and metabolic status of adenomatous polyposis coli (APC) multiple intestinal neoplasia (min) mice was perturbed following 8 weeks of pork meat consumption. Dietary inclusions (15%) of either nitrite-free pork, nitrite-free sausage, or nitrite-containing sausage (frankfurter) were compared against a parallel control group (100% chow). Comprehensive studies investigated: gastrointestinal tract histology (tumours), aberrant crypt foci (ACF), mucin deplin foci (MDF), lipid peroxidation (urine and serum), faecal microbiota, and serum metabolomics (599 metabolites). After 8 weeks mice consuming the frankfurter diet had 53% more (P = 0.014) gastrointestinal tumours than control, although ACF and MDF did not differ. Urine and serum lipid peroxidation markers were 59% (P = 0.001) and 108% (P = 0.001) higher, respectively in the frankfurter group. Gut dysbiosis was evident in these mice with comparably fewer Bacteriodes and more Firmicutes. Fasting serum levels of trimethylamine N-oxide (TMAO) and numerous triglycerides were elevated. Various serum phosphotidylcholine species were decreased. These results demonstrate that nitrite-containing sausages may exaccerbate the development of CRC pathology in APCMin mice to a greater extent than nitrite-free sausages, and this is associated with greater lipid peroxidation, wide-ranging metabolic alternation and gut dysbiosis.PMID:36577751 | DOI:10.1038/s41538-022-00174-y

Addict Biol. 2023 Jan;28(1):e13255. doi: 10.1111/adb.13255.ABSTRACTMethamphetamine (METH) is a commonly abused addictive psychostimulant, and METH-induced neurotoxic and behavioural deficits are in a sex-specific manner. However, there is lack of biomarkers to evaluate METH addiction in clinical practice, especially for gender differences. We utilized ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to detect the serum metabolomics in METH addicts and controls, specially exploring the sex-specific metabolic alterations by METH abuse. We found that many differently expressed metabolites in METH addicts related to metabolisms of amino acid, energy, vitamin and neurological disorders. Further, METH abuse caused different patterns of metabolomics in a sex-specific manner. As to amino acid metabolism, L-phenylalanine, L-tryptophan and L-histidine in serum of male addicts and betaine in serum of female addicts were significantly changed by METH use. In addition, it seemed that purine and pyrimidine-related metabolites (e.g., xanthosine and adenosine 5'-monophosphate) in male and the metabolites of hormone (e.g., cortisol) and folate biosynthesis (e.g., 7,8-dihydrobiopterin and 4-hydroxybenzoic acid) in female were more sensitive to METH addiction. Our findings revealed that L-glutamic acid, L-aspartic acid, alpha-ketoglutarate acid and citric acid may be potential biomarkers for monitoring METH addiction in clinic. Considering sex-specific toxicity by METH, the metabolites of purine and pyrimidine metabolism in male and those of stress-related hormones in female may be used to facilitate the accurate diagnosis and treatment for METH addicts of different genders.PMID:36577725 | DOI:10.1111/adb.13255

Nutr Metab Cardiovasc Dis. 2022 Nov 3:S0939-4753(22)00441-0. doi: 10.1016/j.numecd.2022.10.016. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Reducing consumption of sugar-sweetened beverages (SSBs) is a global public health priority because of their limited nutritional value and associations with increased risk of obesity and metabolic diseases. Gut microbiota-related metabolites emerged as quintessential effectors that may mediate impacts of dietary exposures on the modulation of host commensal microbiome and physiological status.METHODS AND RESULTS: This study assessed the associations among SSBs, circulating microbial metabolites, and gut microbiota-host co-metabolites, as well as metabolic health outcomes in young Chinese adults (n = 86), from the Carbohydrate Alternatives and Metabolic Phenotypes study in Shaanxi Province. Five principal component analysis-derived beverage drinking patterns were determined on self-reported SSB intakes, which were to a varying degree associated with 143 plasma levels of gut microbiota-related metabolites profiled by untargeted metabolomics. Moreover, carbonated beverages, fruit juice, energy drinks, and bubble tea exhibited positive associations with obesity-related markers and blood lipids, which were further validated in an independent cohort of 16,851 participants from the Regional Ethnic Cohort Study in Northwest China in Shaanxi Province. In contrast, presweetened coffee was negatively associated with the obesity-related traits. A total of 79 metabolites were associated with both SSBs and metabolic markers, particularly obesity markers. Pathway enrichment analysis identified the branched-chain amino acid catabolism and aminoacyl-tRNA biosynthesis as linking SSB intake with metabolic health outcomes.CONCLUSION: Our findings demonstrate the associations between habitual intakes of SSBs and several metabolic markers relevant to noncommunicable diseases, and highlight the critical involvement of gut microbiota-related metabolites in mediating such associations.PMID:36577637 | DOI:10.1016/j.numecd.2022.10.016

J Ethnopharmacol. 2022 Dec 25:116074. doi: 10.1016/j.jep.2022.116074. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (AR) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge. AR was the main medicine in a Chinese traditional prescription called Fangji Huangqi Decoction, and it has been used to treating nephrotic syndrome (NS) for thousands of years in China. In recent years, AR has been evidenced to have anti-inflammatory activity, antihyperglycemic activity, antioxidant activity, etc. There are two mainstream commodities for ARs in the market including the imitation wild AR and transplanted AR. However, it is not clear whether the imitation wild AR or transplanted AR and which kind of component, astragalus saponin, astragalus flavonoid or astragalus polysaccharide, makes a bigger contribution in treating NS. And the exact molecular mechanism is not fully understood.AIM OF THE STUDY: To explore which kind of AR and which kind of component in AR makes the bigger contribution in treating NS, and exploring the molecular mechanism.MATERIALS AND METHODS: Firstly, HPLC-UV/ELSD was used for quantitative determination of the constituents in different ARs. Secondly, the efficacy of different ARs treating doxorubicin-induced nephropathy (DN) was compared by metabolomics. Thirdly, the protective effects of different constituents from ARs on the damage of MPC5 cells induced by adriamycin are validated. Finally, the effective constituents and mechanism of ARs against doxorubicin-induced nephropathy were investigated by network pharmacology and molecular docking.RESULTS: Quantitative determination experiment and pharmacological experiment indicated that the AR produced from Gansu province (China) (transplanted AR) with a higher proportion of total saponins, has better efficacy in the treatment for DN. And the cell experiment validated the result that astragalus saponins has the better efficacy in protecting the podocyte against injury than astragalus flavonoids and polysaccharides. The network pharmacology and molecular docking study indicated that astragalus saponins were the main constituent of AR in the treatment for DN. The mechanism may involve in GnRH signaling pathway, VEGF signaling pathway and metabolic pathways, especially of bilirubin metabolism.CONCLUSIONS: Transplanted AR has better efficacy in the treatment for NS than imitation wild AR, astragalus saponins have better efficacy in the treatment for NS than astragalus flavonoids and polysaccharides.PMID:36577490 | DOI:10.1016/j.jep.2022.116074

Cell Rep. 2022 Dec 27;41(13):111891. doi: 10.1016/j.celrep.2022.111891.ABSTRACTCardiogenesis is a tightly regulated dynamic process through a continuum of differentiation and proliferation events. Key factors and pathways governing this process remain incompletely understood. Here, we investigate mice hearts from embryonic day 10.5 to postnatal week 8 and dissect developmental changes in phosphoproteome-, proteome-, metabolome-, and transcriptome-encompassing cardiogenesis and cardiac maturation. We identify mitogen-activated protein kinases as core kinases involved in transcriptional regulation by mediating the phosphorylation of chromatin remodeling proteins during early cardiogenesis. We construct the reciprocal regulatory network of transcription factors (TFs) and identify a series of TFs controlling early cardiogenesis involved in cycling-dependent proliferation. After birth, we identify cardiac resident macrophages with high arachidonic acid metabolism activities likely involved in the clearance of injured apoptotic cardiomyocytes. Together, our comprehensive multi-omics data offer a panoramic view of cardiac development and maturation that provides a resource for further in-depth functional exploration.PMID:36577384 | DOI:10.1016/j.celrep.2022.111891

Cell Rep. 2022 Dec 27;41(13):111867. doi: 10.1016/j.celrep.2022.111867.ABSTRACTThe complexity of signaling events and cellular responses unfolding in neuronal, glial, and immune cells upon traumatic brain injury (TBI) constitutes an obstacle in elucidating pathophysiological links and targets for intervention. We use array phosphoproteomics in a murine mild blunt TBI to reconstruct the temporal dynamics of tyrosine-kinase signaling in TBI and then scrutinize the large-scale effects of perturbation of Met/HGFR, VEGFR1, and Btk signaling by small molecules. We show Met/HGFR as a selective modifier of early microglial response and that Met/HGFR blockade prevents the induction of microglial inflammatory mediators, of reactive microglia morphology, and TBI-associated responses in neurons and vasculature. Both acute and prolonged Met/HGFR inhibition ameliorate neuronal survival and motor recovery. Early elevation of HGF itself in the cerebrospinal fluid of TBI patients suggests that this mechanism has translational value in human subjects. Our findings identify Met/HGFR as a modulator of early neuroinflammation in TBI with promising translational potential.PMID:36577378 | DOI:10.1016/j.celrep.2022.111867

J Plant Physiol. 2022 Dec 23;280:153888. doi: 10.1016/j.jplph.2022.153888. Online ahead of print.ABSTRACTNitrogen (N) is an indispensable element for plant growth and development. To understand the regulation of underlying carbon (C) and N metabolism in blackberry plants, we performed integrated analyses of the physiology, metabolome and transcriptome. Blackberry plants were subjected to no N, nitrate (NO3⁻)-N, ammonium (NH4+)-N and urea treatments. Our results showed that the NH4⁺-N treatment yielded higher values for the biomass, chlorophyll, antioxidants, N contents and antioxidant enzyme activities, as well as lower levels of free radicals and the C/N ratio compared with other treatments. Transcriptome analysis showed that different N forms significantly affected photosynthesis, flavonoid biosynthesis and the TCA cycle. Metabolome analysis indicated that the levels of lipids, carbohydrates, flavonoids and amino acids were markedly changed under different N treatments. Integrated transcriptomic and metabolomic data revealed that amino acids, including proline, arginine, L-isoleucine, L-aspartate, threonine, and L-glutamate, played important roles in maintaining normal plant growth by regulating N metabolism and amino acid metabolism. Overall, blackberry plants preferentially take up NH4⁺-N. Under the NH4⁺-N treatment, N assimilation was stronger, flavonoid biosynthesis was decreased, and the promoting influence of NH4⁺-N on N metabolism was better than that of NO3⁻-N. However, the NO3⁻-N treatment enhanced the C/N ratio, accelerated the process of C metabolism and increased the synthesis of flavonoids, thereby accelerating the flow of N metabolism to C metabolism. These results provide deeper insight into coordinating C and N metabolism and improving N use efficiency in blackberry plants.PMID:36577314 | DOI:10.1016/j.jplph.2022.153888

CEN Case Rep. 2022 Dec 28. doi: 10.1007/s13730-022-00768-1. Online ahead of print.ABSTRACTAdenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that leads to the accumulation of poorly soluble 2,8-dihydroxyadenine (DHA) in the kidneys, resulting in a variety of renal presentations including nephrolithiasis, acute kidney injury, and chronic kidney disease (CKD) caused by crystal nephropathy. Here, we report a case of a 43-year-old man with 2,8-DHA crystalline nephropathy caused by APRT deficiency strongly suspected by renal biopsy results and definitively diagnosed by a urine gas chromatography-mass spectrometry (GC/MS)-based plasma metabolomic assessment. This case represents the importance of awareness and recognition of the signs and symptoms of this rare condition and its progression to CKD, which can be prevented by the early administration of xanthine oxidoreductase inhibitors.PMID:36576711 | DOI:10.1007/s13730-022-00768-1

Metabolomics. 2022 Dec 28;19(1):4. doi: 10.1007/s11306-022-01965-w.ABSTRACTINTRODUCTION: Feature annotation is crucial in untargeted metabolomics but remains a major challenge. The large pool of metabolites collected under various instrumental conditions is underrepresented in publicly available databases. Retention time (RT) and collision cross section (CCS) measurements from liquid chromatography ion mobility high-resolution mass spectrometers can be employed in addition to MS/MS spectra to improve the confidence of metabolite annotation. Recent advancements in machine learning focus on improving the accuracy of predictions for CCS and RT values. Therefore, high-quality experimental data are crucial to be used either as training datasets or as a reference for high-confidence matching.METHODS: This manuscript provides an easy-to-use workflow for the creation of an in-house metabolite library, offers an overview of alternative solutions, and discusses the challenges and advantages of using open-source software. A total of 100 metabolite standards from various classes were analyzed and subjected to the described workflow for library generation.RESULTS AND DISCUSSION: The outcome was an open-access available NIST format metabolite library (.msp) with multidimensional information. The library was used to evaluate CCS prediction tools, MS/MS spectra heterogeneities (e.g., multiple adducts, in-source fragmentation, radical fragment ions using collision-induced dissociation), and the reporting of RT.PMID:36576608 | DOI:10.1007/s11306-022-01965-w

Anal Chem. 2022 Dec 28. doi: 10.1021/acs.analchem.2c04203. Online ahead of print.ABSTRACTNuclear magnetic resonance (NMR) spectroscopy is commonly employed in a wide range of metabolomic research. Unfortunately, due to its relatively low sensitivity, smaller samples become challenging to study by NMR. Cryoprobes can be used to increase sensitivity by cooling the coil and preamplifier, offering sensitivity improvements of ∼3 to 4x. Alternatively, microcoils can be used to increase mass sensitivity by improving sample filling and proximity, along with decreased electrical resistance. Unfortunately, combining the two approaches is not just technically challenging, but as the coil decreases, so does its thermal fingerprint, reducing the advantage of cryogenic cooling. Here, an alternative solution is proposed in the form of a Lenz lens inside a cryoprobe. Rather than replacing the detection coil, Lenz lenses allow the B1 field from a larger coil to be refocused onto a much smaller sample area. In turn, the stronger B1 field at the sample provides strong coupling to the cryocoil, improving the signal. By combining a 530 I.D. Lenz lens with a cryoprobe, sensitivity was further improved by 2.8x and 3.5x for 1H and 13C, respectively, over the cryoprobe alone for small samples. Additionally, the broadband nature of the Lenz lenses allowed multiple nuclei to be studied and heteronuclear two-dimensional (2D) NMR approaches to be employed. The sensitivity improvements and 2D capabilities are demonstrated on 430 nL of hemolymph and eight eggs (∼350 μm O.D.) from the model organismDaphnia magna. In summary, combining Lenz lenses with cryoprobes offers a relatively simple approach to boost sensitivity for tiny samples while retaining cryoprobe advantages.PMID:36576271 | DOI:10.1021/acs.analchem.2c04203

Circ Res. 2022 Dec 28. doi: 10.1161/CIRCRESAHA.122.321975. Online ahead of print.ABSTRACTBACKGROUND: Dysbiosis of gut microbiota plays a pivotal role in vascular dysfunction and microbial diversity was reported to be inversely correlated with arterial stiffness. However, the causal role of gut microbiota in the progression of arterial stiffness and the specific species along with the molecular mechanisms underlying this change remain largely unknown.METHODS: Participants with elevated arterial stiffness and normal controls free of medication were matched for age and sex. The microbial composition and metabolic capacities between the 2 groups were compared with the integration of metagenomics and metabolomics. Subsequently, AngII (angiotensin II)-induced and humanized mouse model were employed to evaluate the protective effect of Flavonifractor plautii (F. plautii) and its main effector cis-aconitic acid.RESULTS: Human fecal metagenomic sequencing revealed a significantly high abundance and centrality of F. plautii in normal controls, which was absent in the microbial community of subjects with elevated arterial stiffness. Moreover, blood pressure only mediated part of the effect of F. plautii on lower arterial stiffness. The microbiome of normal controls exhibited an enhanced capacity for glycolysis and polysaccharide degradation, whereas, those of subjects with increased arterial stiffness were characterized by increased biosynthesis of fatty acids and aromatic amino acids. Integrative analysis with metabolomics profiling further suggested that increased cis-aconitic acid served as the main effector for the protective effect of F. plautii against arterial stiffness. Replenishment with F. plautii and cis-aconitic acid improved elastic fiber network and reversed increased pulse wave velocity through the suppression of MMP-2 (matrix metalloproteinase-2) and inhibition of MCP-1 (monocyte chemoattractant protein-1) and NF-κB (nuclear factor kappa-B) activation in both AngII-induced and humanized model of arterial stiffness.CONCLUSIONS: Our translational study identifies a novel link between F. plautii and arterial function and raises the possibility of sustaining vascular health by targeting gut microbiota.PMID:36575982 | DOI:10.1161/CIRCRESAHA.122.321975