PubMed

Emerg Med Int. 2023 Jun 13;2023:2590115. doi: 10.1155/2023/2590115. eCollection 2023.ABSTRACTCurrent prognostic biomarkers for sepsis have limited sensitivity and specificity. This study aimed to investigate dynamic lipid metabolomics and their association with septic immune response and clinical outcomes of sepsis. This prospective cohort study included patients with sepsis who met the Sepsis 3.0 criteria. On hospitalization days 1 (D1) and 7 (D7), plasma samples were collected, and patients underwent liquid chromatography with tandem mass spectrometry. A total of 40 patients were enrolled in the study, 24 (60%) of whom were men. The median age of the enrolled patients was 81 (68-84) years. Thirty-one (77.5%) patients had a primary infection site of the lung. Participants were allocated to the survivor (25 cases) and nonsurvivor (15 cases) groups based on their 28-day survival status. Ultimately, a total of 113 lipids were detected in plasma samples on D 1 and D 7, of which 42 lipids were most abundant in plasma samples. The nonsurvival group had significantly lower lipid expression levels in lysophosphatidylcholine (LysoPC) (16 : 0, 17 : 0,18 : 0) and 18 : 1 SM than those in the survival group (p < 0.05) on D7-D1. The correlation analysis showed that D7-D1 16 : 0 LysoPC (r = 0.367, p = 0.036),17 : 0 LysoPC (r = 0.389, p = 0.025) and 18 : 0 LysoPC(r = 0.472, p = 0.006) levels were positively correlated with the percentage of CD3+ T cell in the D7-D1. Plasma LysoPC and SM changes may serve as prognostic biomarkers for sepsis, and lipid metabolism may play a role in septic immune disturbances.PMID:37346225 | PMC:PMC10281824 | DOI:10.1155/2023/2590115

Chem Biodivers. 2023 Jun 22:e202300552. doi: 10.1002/cbdv.202300552. Online ahead of print.ABSTRACTLight-emitting plants (LEPs) provides light in areas without electricity. The phosphorescent compound was used as a lighting material for LEP development. However, using the phosphorescent compound for LEPs development required optimization and phytotoxicity evaluation. Strontium aluminate (SrAl2O4) is a phosphorescent compound that can glow for a long time and is easily recharged by visible light. In this study, using SrAl2O4 to develop LEPs was evaluated. Additionally, plant stress under SrAl2O4 was investigated. Metabolomic analysis can explain the possible mechanism of plants' stress under SrAl2O4. After, injecting 3 mL of 5% (w/v) SrAl2O4 products 1, 2, and 3 into the stem of Ipomoea aquatica, the result showed that SrAl2O4 products 2 and 3 caused oxidative stress. The metabolomic analysis also indicated that I. aquatica responded to SrAl2O4 product 1 by increasing pipecolic acid and salicylic acid, while I. aquatica injected with SrAl2O4 products 2 and 3 showed a decrease in salicylic acid around 0.005 and 0.061-fold, respectively, compared to control plants. and an excess accumulation of MDA around 10.00-12.00 µmol g-1 FW. A 15% concentration of SrAl2O4 can be used for LEPs development, enabling photoemission 18-fold for 50 minutes. SrAl2O4 product 1 has the potential to be a material for LEPs.PMID:37345919 | DOI:10.1002/cbdv.202300552

J Am Heart Assoc. 2023 Jun 22:e029542. doi: 10.1161/JAHA.123.029542. Online ahead of print.ABSTRACTBackground Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post-transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25-1.90]; P<0.001), with similar effects in each validation cohort. This metabolite score of diastolic function was simultaneously associated with measures of multimorbidity, suggesting a metabolic link between cardiac and noncardiac state in aortic stenosis. Conclusions Metabolite profiles of cardiac structure identify individuals at high risk for death following transcatheter aortic valve implantation and concurrent multimorbidity. These results call for efforts to address potentially reversible metabolic biology associated with risk to optimize post-transcatheter aortic valve implantation recovery, rehabilitation, and survival.PMID:37345820 | DOI:10.1161/JAHA.123.029542

J Agric Food Chem. 2023 Jun 22. doi: 10.1021/acs.jafc.3c01881. Online ahead of print.ABSTRACT3,5,6,7,8,3',4'-Heptamethoxyflavone (HMF) could prevent obesity and hyperlipidemia, but its effects on gut microbiota and fecal metabolites remain unclear. Here, the effect of HMF on metabolic syndrome (MS) was evaluated in high-fat diet (HFD)-fed mice, and its underlying mechanisms were revealed by integrative metagenomic and metabolomic analyses. We demonstrated that HMF could effectively ameliorate HFD-induced MS by alleviating body-weight gain, fat accumulation, hepatic steatosis, and lipid and glucose abnormalities. HMF significantly altered the gut microbiota composition in HFD-fed mice with enrichment of short-chain fatty acid (SCFA)- and bile acid-producing beneficial bacteria and inhibition of harmful bacteria. Also, HMF improved microbial functions by up-regulating bile acid metabolism and down-regulating fatty acid metabolism and inflammatory response-related pathways. Consistent with the gut microbial changes, HMF altered the fecal metabolite profile of HFD-fed mice, mainly characterized by increasing SCFA and several bile acid levels as well as lowering several lysophospholipids and fatty acid levels. Correlation analysis indicated that three key species Faecalibaculum rodentium, Collinsella aerofaciens, and Lactobacillus fermentum and the increase in microbial metabolites, i.e., SCFAs and secondary bile acids, might play a positive role in alleviating MS. Our results suggested that HMF alleviated HFD-induced MS possibly by modulating the composition, function, and metabolism of gut microbiota.PMID:37345674 | DOI:10.1021/acs.jafc.3c01881

New Phytol. 2023 Jun 21. doi: 10.1111/nph.19068. Online ahead of print.ABSTRACTPlants rely on cross-resistance traits to defend against multiple, phylogenetically distinct enemies. These traits are often the result of long co-evolutionary histories. Biological invasions can force naïve plants to cope with novel, coincident pests, and pathogens. For example, European ash (Fraxinus excelsior) is substantially threatened by the emerald ash borer (EAB), Agrilus planipennis, a wood-boring beetle, and the ash dieback (ADB) pathogen, Hymenoscyphus fraxineus. Yet, plant cross-resistance traits against novel enemies are poorly explored and it is unknown whether naïve ash trees can defend against novel enemy complexes via cross-resistance mechanisms. To gain mechanistic insights, we quantified EAB performance on grafted replicates of ash genotypes varying in ADB resistance and characterized ash phloem chemistry with targeted and untargeted metabolomics. Emerald ash borer performed better on ADB-susceptible than on ADB-resistant genotypes. Moreover, changes in EAB performance aligned with differences in phloem chemical profiles between ADB-susceptible and ADB-resistant genotypes. We show that intraspecific variation in phloem chemistry in European ash can confer increased cross-resistance to invasive antagonists from different taxonomic kingdoms. Our study suggests that promotion of ADB-resistant ash genotypes may simultaneously help to control the ADB disease and reduce EAB-caused ash losses, which may be critical for the long-term stability of this keystone tree species.PMID:37345294 | DOI:10.1111/nph.19068

Cancers (Basel). 2023 May 16;15(10):2780. doi: 10.3390/cancers15102780.ABSTRACTBreast cancer has now become the most commonly diagnosed cancer, accounting for one in eight cancer diagnoses worldwide. Non-invasive diagnostic biomarkers and associated tests are superlative candidates to complement or improve current approaches for screening, early diagnosis, or prognosis of breast cancer. Biomarkers detected from body fluids such as blood (serum/plasma), urine, saliva, nipple aspiration fluid, and tears can detect breast cancer at its early stages in a minimally invasive way. The advancements in high-throughput molecular profiling (omics) technologies have opened an unprecedented opportunity for unbiased biomarker detection. However, the irreproducibility of biomarkers and discrepancies of reported markers have remained a major roadblock to clinical implementation, demanding the investigation of contributing factors and the development of standardised biomarker discovery pipelines. A typical biomarker discovery workflow includes pre-analytical, analytical, and post-analytical phases, from sample collection to model development. Variations introduced during these steps impact the data quality and the reproducibility of the findings. Here, we present a comprehensive review of methodological variations in biomarker discovery studies in breast cancer, with a focus on non-nucleotide biomarkers (i.e., proteins, lipids, and metabolites), highlighting the pre-analytical to post-analytical variables, which may affect the accurate identification of biomarkers from body fluids.PMID:37345117 | DOI:10.3390/cancers15102780

Cancers (Basel). 2023 May 10;15(10):2676. doi: 10.3390/cancers15102676.ABSTRACTThe complex molecular alterations that underlie cancer pathophysiology are studied in depth with omics methods using bulk tissue extracts. For spatially resolved tissue diagnostics using needle biopsy cores, however, histopathological analysis using stained FFPE tissue and the immunohistochemistry (IHC) of a few marker proteins is currently the main clinical focus. Today, spatial omics imaging using MSI or IRI is an emerging diagnostic technology for the identification and classification of various cancer types. However, to conserve tissue-specific metabolomic states, fast, reliable, and precise methods for the preparation of fresh-frozen (FF) tissue sections are crucial. Such methods are often incompatible with clinical practice, since spatial metabolomics and the routine histopathology of needle biopsies currently require two biopsies for FF and FFPE sampling, respectively. Therefore, we developed a device and corresponding laboratory and computational workflows for the multimodal spatial omics analysis of fresh-frozen, longitudinally sectioned needle biopsies to accompany standard FFPE histopathology of the same biopsy core. As a proof-of-concept, we analyzed surgical human liver cancer specimens using IRI and MSI with precise co-registration and, following FFPE processing, by sequential clinical pathology analysis of the same biopsy core. This workflow allowed for a spatial comparison between different spectral profiles and alterations in tissue histology, as well as a direct comparison for histological diagnosis without the need for an extra biopsy.PMID:37345020 | DOI:10.3390/cancers15102676

Clin Nutr ESPEN. 2023 Aug;56:83-86. doi: 10.1016/j.clnesp.2023.04.031. Epub 2023 May 5.ABSTRACTINTRODUCTION: Nicotinamide adenine dinucleotide (NAD+) is a coenzyme of the NAD+-dependent protein deacetylase sirtuin-1 (SIRT1). An increase in NAD+ concentration induces SIRT1 activation that results in various health benefits. Since nicotinamide mononucleotide (NMN) is a precursor of NAD+, NMN ingestion is expected to have multiple health benefits such as alleviation of aging, lifestyle-related and neurodegenerative diseases, through the activation of SIRT1. In this study, we aimed to determine the effects of daily NMN ingestion on plasma levels of NMN and NAD+.METHODS: Healthy volunteers received 250 mg of NMN once a day in the morning (n = 11) for 12 weeks, and the plasma concentrations of NMN and NAD+ were measured monthly. Physiological and laboratory tests were performed within 2 h after lunch (at 2 pm) before and during NMN administration.RESULTS: Oral administration of NMN increased the plasma concentrations of NMN and NAD+, and the postprandial serum insulin levels. The elevation levels of NMN and insulin varied widely among individuals. No adverse symptoms were observed in the participants.CONCLUSIONS: Oral administration of NMN elevates plasma levels of NMN and NAD+, and postprandial serum insulin levels.PMID:37344088 | DOI:10.1016/j.clnesp.2023.04.031

J Therm Biol. 2023 May;114:103563. doi: 10.1016/j.jtherbio.2023.103563. Epub 2023 Apr 7.ABSTRACTThermal burn injury is a severe and life-threatening form of trauma that presents a significant challenge to clinical therapy. Therapeutic hypothermia has been shown to be beneficial in various human pathologies. Adenosine triphosphate (ATP) induces a hypothermic state that resembles hibernation-like suspended animation in mammals. This study investigates the potential protective role of ATP-induced hypothermia in thermal burn injury. Male C57BL/6 mice underwent a sham procedure or third-degree burn, and ATP-induced hypothermia was applied immediately or 1 h after burn injury. Our results show that ATP-induced hypothermia significantly improved burn depth progression and reduced collagen degradation. Moreover, hypothermia induced by ATP alleviated burn-induced hyperinflammatory responses and oxidative stress. Metabolomic profiling revealed that ATP-induced hypothermia reversed the shifts of metabolic profiles of the skin in burn mice. In addition, ATP-induced hypothermia relieved nociceptive and inflammatory pain, as observed in the antinociceptive test. Our findings suggest that ATP-induced hypothermia attenuates burn injury and provides new insights into first-aid therapy after thermal burn injury.PMID:37344025 | DOI:10.1016/j.jtherbio.2023.103563

Bioresour Technol. 2023 Jun 19:129366. doi: 10.1016/j.biortech.2023.129366. Online ahead of print.ABSTRACTA bottleneck of microalgae-based techniques for wastewater bioremediation is activity inhibition of microalgae by toxic pollutants. The defense strategies of Chlorella sorokinana against toxic pyridine were studied. Results indicated that pyridine caused photoinhibition and reactive oxygen species overproduction in a concentration-dependent manner. The 50% inhibitory concentration of pyridine (147 mg L-1) destroyed C/N balance, disrupted multiple metabolic pathways of C. sorokinana. In response to pyridine stress, ascorbate peroxidase and catalase activities increased to scavenge reactive oxygen species under pyridine concentrations lower than 23 mg L-1. At higher pyridine concentrations, the activation of calcium signaling pathways and phytohormones represented the predominant defense response. Extracellular polymeric substances increased 3.6-fold in 147 mg L-1 group than control, which interacted with pyridine through hydrophobic and aromatic stacking to resist pyridine entering algal cells. Unraveling the intracellular and extracellular self-defense mechanisms of microalgae against pyridine stress facilitates the development of microalgal-based technology in wastewater bioremediation.PMID:37343803 | DOI:10.1016/j.biortech.2023.129366

Environ Toxicol Pharmacol. 2023 Jun 19:104191. doi: 10.1016/j.etap.2023.104191. Online ahead of print.ABSTRACTCo-exposure of tetracycline (TC) and polyethylene microplastic (MP-PE) pollution might result in more intricate effects on rice growth and grain quality. In present study, two different rice cultivars of contrasting drought tolerance, Hanyou73 (H73, drought-resistant) and Quanyou280 (Q280, drought-sensitive) were grown on MP-PE and TC-contaminated soils under drought. It was found that drought stress had different influence on TC accumulation in the two rice cultivars. H73 accumulated more TC in leaves and grains without drought stress while Q280 accumulated more TC under drought stress. Furthermore, metabolomics results demonstrated that under drought stress, about 80% of metabolites in H73 and 95% in Q280 were down-regulated as compared to non-drought treatments. These findings provide insights into the effects of TC and MP-PE with and without drought stress on potential risks to rice growth and grain quality, which has implications on rice production and cultivar election under multiple-stress conditions.PMID:37343773 | DOI:10.1016/j.etap.2023.104191

Ageing Res Rev. 2023 Jun 19:101987. doi: 10.1016/j.arr.2023.101987. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is determined by various pathophysiological mechanisms starting 10 to 25 years before the onset of clinical symptoms. As multiple functionally interconnected molecular/cellular pathways appear disrupted in AD, the exploitation of high-throughput unbiased omics sciences is critical to elucidating the precise pathogenesis of AD. Among different omics, metabolomics is a fast-growing discipline allowing for the simultaneous detection and quantification of hundreds/thousands of perturbed metabolites in tissues or biofluids, reproducing the fluctuations of multiple networks affected by a disease. Here, we seek to critically depict the main metabolomics methodologies with the aim of identifying new potential AD biomarkers and further elucidating AD pathophysiological mechanisms. From a systems biology perspective, as metabolic alterations can occur before the development of clinical signs, metabolomics - coupled with existing accessible biomarkers used for AD screening and diagnosis - can support early disease diagnosis and help develop individualized treatment plans. Presently, the majority of metabolomic analyses emphasized that lipid metabolism is the most consistently altered pathway in AD pathogenesis. The possibility that metabolomics may reveal crucial steps in AD pathogenesis is undermined by the difficulty in discriminating between the causal or epiphenomenal or compensatory nature of metabolic findings.PMID:37343679 | DOI:10.1016/j.arr.2023.101987

Chemosphere. 2023 Jun 19:139222. doi: 10.1016/j.chemosphere.2023.139222. Online ahead of print.ABSTRACTHitherto, the effect of vanadium on higher plant growth remains an open topic. Therefore, nontargeted metabolomic and RNA-Seq profiling were implemented to unravel the possible alteration in alfalfa seedlings subjected to 0.1 mg L-1 (B group) and 0.5 mg L-1 (C group) pentavalent vanadium [(V(V)] versus control (A group) in this study. Results revealed that vanadium exposure significantly altered some pivotal transcripts and metabolites. The number of differentially expressed genes (DEGs) markedly up- and down-regulated was 21 and 23 in B_vs_A, 27 and 33 in C_vs_A, and 24 and 43 in C_vs_B, respectively. The number for significantly up- and down-regulated differential metabolites was 17 and 15 in B_vs_A, 43 and 20 in C_vs_A, and 24 and 16 in C_vs_B, respectively. Metabolomics and transcriptomics co-analysis characterized three significantly enriched metabolic pathways in C_vs_A comparing group, viz., α-linolenic acid metabolism, flavonoid biosynthesis, and phenylpropanoid biosynthesis, from which some differentially expressed genes and differential metabolites participated. The metabolite of traumatic acid in α-linolenic acid metabolism and apigenin in flavonoid biosynthesis were markedly upregulated, while phenylalanine in phenylpropanoid biosynthesis was remarkably downregulated. The genes of allene oxide cyclase (AOC) and acetyl-CoA acyltransferase (fadA) in α-linolenic acid metabolism, and chalcone synthase (CHS), flavonoid 3'-monooxygenase (CYP75B1), and flavonol synthase (FLS) in flavonoid biosynthesis, and caffeoyl-CoA O-methyltransferase (CCoAOMT) in phenylpropanoid biosynthesis were significantly downregulated. While shikimate O-hydroxycinnamoyltransferase (HCT) in flavanoid and phenylpropanoid biosynthesis were conspicuously upregulated. Briefly, vanadium exposure induces a readjustment yielding in metabolite and the correlative synthetic precursors (transcripts/unigenes) in some branched metabolic pathways. This study provides a practical and in-depth perspective from transcriptomics and metabolomics in investigating the effects conferred by vanadium on plant growth and development.PMID:37343642 | DOI:10.1016/j.chemosphere.2023.139222

Meat Sci. 2023 Jun 15;204:109255. doi: 10.1016/j.meatsci.2023.109255. Online ahead of print.ABSTRACTPrecursors to flavor are important to its development, yet little is known about the intrinsic products of metabolism that influence flavor. Our objective was to use untargeted metabolomics and volatile aroma compounds to predict expert and consumer sensory traits. USDA Select and upper 2/3 Choice beef strip loins were wet aged for 10 or 20 d and then cut into steaks, vacuum-packaged, and frozen. Steaks were cooked to 63 °C, 71 °C, or 80 °C end-point internal steak temperature. USDA Choice steaks had more intense beef flavor identity, brown, roasted, fat-like, salty, sweet, sour, umami, buttery, and overall sweet flavors compared to USDA Select steaks (P < 0.05). Steaks cooked to 80 °C had more intense beef identity, brown, roasted, and umami flavors than steaks cooked to a lower degree of doneness. Steaks cooked to either 63 °C or 71 °C had more intense bloody, metallic, and sour flavors and were juicier, more tender, and had less connective tissue than steaks cooked to a higher degree of doneness. Volatile aroma compounds increased (P < 0.05) in Choice steaks aged for 20 d, while cooking steaks to 80 increased aldehydes, ketones, and pyrazines. Raw steaks had 69 small-molecule metabolomic compounds shared across all four quality grade x aging combinations, and discriminant analysis correctly categorized (P < 0.05) these metabolites. Metabolites and volatiles can be used to predict (r2 > 0.85) expert and consumer sensory panel descriptors and liking.PMID:37343480 | DOI:10.1016/j.meatsci.2023.109255

EBioMedicine. 2023 Jun 19;93:104650. doi: 10.1016/j.ebiom.2023.104650. Online ahead of print.ABSTRACTBACKGROUND: Pyrimidine nucleotides fuel the growth of colorectal cancer (CRC), making their associated proteins potential targets for cancer intervention. Uridine-Cytidine Kinase Like-1(UCKL1) is an enzyme involved in the pyrimidine salvage pathway. It is highly expressed in multiple cancers. But the function and underlying mechanism of UCKL1 in CRC are yet to study.METHODS: Large-scale genomic analysis was performed to search for potential CRC players related to pyrimidine metabolism. The function of UCKL1 in CRC were examined by RNA interference coupled with in vitro and in vivo assays. GSH/GSSG assay, NADP+ assay, ROS, and Lipid peroxidation assays were performed to check the function of UCKL1 in ferroptosis. Metabolomics analyses, RNA sequencing, western blotting, and rescue assays were done to reveal the underlying mechanisms of UCKL1. Xenograft mouse model was used to examine the therapeutic potential of UCKL1 as a target in combination with other ferroptosis inducers.FINDINGS: UCKL1 was identified to repress ferroptosis in CRC cells. It was highly expressed in CRC. It regulated CRC cells proliferation and migration. Downregulation of UCKL1 led to enhanced tumour lipid peroxidation. Intriguingly, UCKL1 reduction-mediated ferroptosis was not related to its role in catalyzing uridine monophosphate (UMP) and cytidine monophosphate (CMP) synthesis. Instead, UCKL1 stabilized Nrf2, which in turn promoted the expression of SLC7A11, a classical repressor of ferroptosis. Moreover, downregulation of UCKL1 sensitized CRC cells to GPX4 inhibitors in vitro and in vivo.INTERPRETATION: Our study demonstrates that UCKL1 plays a non-canonical role in repressing ferroptosis through a UCKL1-Nrf2-SLC7A11 axis in CRC cells. Combinatorial strategy in targeting ferroptosis by depletion of UCKL1 and application of GPX4 inhibitors may serve as a new effective method for CRC treatment.FUNDING: This study was supported in part by fund from National Natural Science Foundation of China (Grant No. 31970674 to PY), by the Basic and Applied Basic Research Program of Guangdong Province (Grant No. 2023A1515030245 to KL), by the program of Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), and by National Key Clinical Discipline.PMID:37343364 | DOI:10.1016/j.ebiom.2023.104650

BMC Genomics. 2023 Jun 21;24(1):342. doi: 10.1186/s12864-023-09457-4.ABSTRACTBACKGROUND: Tibetan chickens (Gallus gallus; TBCs), an indigenous breed distributed in the Qinghai-Tibet Plateau, are well adapted to the hypoxic environment. Currently, the molecular genetic basis of hypoxia adaptation in TBCs remains unclear. This study investigated hypoxia adaptation patterns of embryonic brain at different development stages by integrating analysis of the transcriptome with our previously published metabolome data in TBCs and Dwarf Laying Chickens (DLCs), a lowland chicken breed.RESULTS: During hypoxia, the results revealed that 1334, 578, and 417 differentially expressed genes (DEGs) (|log2 fold change|>1, p-value < 0.05) on days 8, 12, and 18 of development, respectively between TBCs and DLCs. Gene Ontology (GO) and pathway analyses revealed that DEGs are mainly related to metabolic pathways, vessel development, and immune response under hypoxia. This is consistent with our metabolome data that TBCs have higher energy metabolism than DLCs during hypoxia. Some vital DEGs between TBCs and DLCs, such as EPAS1, VEGFD, FBP1, FBLN5, LDHA, and IL-6 which are involved in the HIF pathway and hypoxia regulation.CONCLUSION: These results suggest varied adaptation patterns between TBCs and DLCs under hypoxia. Our study provides a basis for uncovering the molecular regulation mechanism of hypoxia adaptation in TBCs and a potential application of hypoxia adaptation research for other animals living on the Qinghai-Tibet Plateau, and may even contribute to the study of brain diseases caused by hypoxia.PMID:37344809 | DOI:10.1186/s12864-023-09457-4

Metabolomics. 2023 Jun 21;19(7):60. doi: 10.1007/s11306-023-02024-8.ABSTRACTINTRODUCTION: Breast cancer is the most diagnosed tumor and the leading cause of cancer death in women worldwide. Metabolomics allows the quantification of the entire set of metabolites in blood samples, making it possible to study differential metabolomics patterns related to neoadjuvant treatment in the breast cancer neoadjuvant setting.OBJECTIVES: Characterizing metabolic differences in breast cancer blood samples according to their response to neoadjuvant treatment.METHODS: One hundred and three plasma samples of breast cancer patients, before receiving neoadjuvant treatment, were analyzed through UPLC-MS/MS metabolomics. Then, metabolomics data were analyzed using probabilistic graphical models and biostatistics methods.RESULTS: Metabolomics data allowed the identification of differences between groups according to response to neoadjuvant treatment. These differences were specific to each breast cancer subtype. Patients with HER2+ tumors showed differences in metabolites related to amino acids and carbohydrates pathways between the two pathological response groups. However, patients with triple-negative tumors showed differences in metabolites related to the long-chain fatty acids pathway. Patients with Luminal B tumors showed differences in metabolites related to acylcarnitine pathways.CONCLUSIONS: It is possible to identify differential metabolomics patterns between complete and partial responses to neoadjuvant therapy, being this metabolomic profile specific for each breast cancer subtype.PMID:37344702 | DOI:10.1007/s11306-023-02024-8

J Agric Food Chem. 2023 Jun 21. doi: 10.1021/acs.jafc.3c01493. Online ahead of print.ABSTRACTA total of 718 metabolites were identified in leaves and seeds of the soybean (Glycine max (L.) Merr., Fabaceae) fast neutron (FN) mutant 2012CM7F040p05ar154bMN15, which was previously shown to have 21 genes deleted and higher protein content in seeds as compared to wild-type. Among the identified metabolites, 164 were found only in seeds, 89 only in leaves, and 465 in both leaves and seeds. Metabolites that exhibited higher abundance in the mutant leaf than in the wild type include the flavonoids afromosin, biochanin A, dihydrodaidzein, and apigenin. Mutant leaves also exhibited a higher accumulation of glycitein-glucoside, dihydrokaempferol, and pipecolate. The seed-only metabolites that were found in higher abundance in the mutant compared to the wild type included 3-hydroxybenzoate, 3-aminoisobutyrate, coenzyme A, N-acetyl-β-alanine, and 1-methylhistidine. Among several amino acids, the cysteine content increased in the mutant leaf and seed when compared to the wild type. We anticipate that the deletion of acetyl-CoA synthase created a negative feedback effect on carbon dynamics, resulting in increased amounts of cysteine and isoflavone-associated metabolites. Metabolic profiling provided new insight into the cascading effect of gene deletions that helps breeders to produce value-added nutritional seed traits.PMID:37343237 | DOI:10.1021/acs.jafc.3c01493

Eur Thyroid J. 2023 Jun 1:ETJ-23-0062. doi: 10.1530/ETJ-23-0062. Online ahead of print.ABSTRACTBACKGROUND: Hypothyroidism is clinically characterized by decrease in levels of the circulating thyroid hormones namely thyroxine and triiodothyronine. The main treatment for hypothyroidism is thyroid hormone replacement using levothyroxine to normalize serum thyroid hormone levels.OBJECTIVES: In this study, we explored the metabolic changes in the plasma of patients with hypothyroidism after reaching a euthyroid state with levothyroxine treatment.METHODS: Plasma samples from 18 patients diagnosed as overt hypothyroidism were collected before and after levothyroxine treatment upon reaching a euthyroid state and were analyzed by high-resolution mass spectrometry-based metabolomics. Multivariate and univariate analyses evaluated data to highlight potential metabolic biomarkers.RESULTS: LC-MS-based metabolomics revealed significant decrease in the levels of ceramide, phosphatidylcholine, triglycerides, acylcarnitine, and peptides after levothyroxine treatment; this could indicate a change in the fatty acid transportation system and an enhanced β oxidation, compared with a hypothyroid state. At the same time, the decrease in the peptides suggested a shift in protein synthesis. In addition, there was a considerable rise in glycocholic acid following therapy, suggesting the involvement of thyroid hormones in stimulating bile acid production and secretion.CONCLUSIONS: A metabolomic analysis of patients with hypothyroidism revealed significant changes in several metabolites and lipids after treatment. This study showed the value of the metabolomics technique in providing a complementary understanding of the pathophysiology of hypothyroidism and as a crucial tool for examining the molecular impact of LT4 treatment on hypothyroidism. It was an important tool for investigating the therapeutic effects of levothyroxine on hypothyroidism at the molecular level.PMID:37343156 | DOI:10.1530/ETJ-23-0062

Front Pharmacol. 2023 Jun 5;14:1100542. doi: 10.3389/fphar.2023.1100542. eCollection 2023.ABSTRACTHigh prevalence of parasitic or bacterial infectious diseases in some world areas is due to multiple reasons, including a lack of an appropriate health policy, challenging logistics and poverty. The support to research and development of new medicines to fight infectious diseases is one of the sustainable development goals promoted by World Health Organization (WHO). In this sense, the traditional medicinal knowledge substantiated by ethnopharmacology is a valuable starting point for drug discovery. This work aims at the scientific validation of the traditional use of Piper species ("Cordoncillos") as firsthand anti-infectious medicines. For this purpose, we adapted a computational statistical model to correlate the LCMS chemical profiles of 54 extracts from 19 Piper species to their corresponding anti-infectious assay results based on 37 microbial or parasites strains. We mainly identified two groups of bioactive compounds (called features as they are considered at the analytical level and are not formally isolated). Group 1 is composed of 11 features being highly correlated to an inhibiting activity on 21 bacteria (principally Gram-positive strains), one fungus (C. albicans), and one parasite (Trypanosoma brucei gambiense). The group 2 is composed of 9 features having a clear selectivity on Leishmania (all strains, both axenic and intramacrophagic). Bioactive features in group 1 were identified principally in the extracts of Piper strigosum and P. xanthostachyum. In group 2, bioactive features were distributed in the extracts of 14 Piper species. This multiplexed approach provided a broad picture of the metabolome as well as a map of compounds putatively associated to bioactivity. To our knowledge, the implementation of this type of metabolomics tools aimed at identifying bioactive compounds has not been used so far.PMID:37342590 | PMC:PMC10278888 | DOI:10.3389/fphar.2023.1100542