PubMed

Transfus Med Hemother. 2023 Mar 8;50(3):174-183. doi: 10.1159/000529744. eCollection 2023 Jun.ABSTRACTBACKGROUND: Blood transfusion is a life-saving intervention for millions of recipients worldwide. Over the last 15 years, the advent of high-throughput, affordable omics technologies - including genomics, proteomics, lipidomics, and metabolomics - has allowed transfusion medicine to revisit the biology of blood donors, stored blood products, and transfusion recipients.SUMMARY: Omics approaches have shed light on the genetic and non-genetic factors (environmental or other exposures) impacting the quality of stored blood products and efficacy of transfusion events, based on the current Food and Drug Administration guidelines (e.g., hemolysis and post-transfusion recovery for stored red blood cells). As a treasure trove of data accumulates, the implementation of machine learning approaches promises to revolutionize the field of transfusion medicine, not only by advancing basic science. Indeed, computational strategies have already been used to perform high-content screenings of red blood cell morphology in microfluidic devices, generate in silico models of erythrocyte membrane to predict deformability and bending rigidity, or design systems biology maps of the red blood cell metabolome to drive the development of novel storage additives.KEY MESSAGE: In the near future, high-throughput testing of donor genomes via precision transfusion medicine arrays and metabolomics of all donated products will be able to inform the development and implementation of machine learning strategies that match, from vein to vein, donors, optimal processing strategies (additives, shelf life), and recipients, realizing the promise of personalized transfusion medicine.PMID:37434999 | PMC:PMC10331163 | DOI:10.1159/000529744

Front Oncol. 2023 Jun 26;13:1234242. doi: 10.3389/fonc.2023.1234242. eCollection 2023.NO ABSTRACTPMID:37434972 | PMC:PMC10331834 | DOI:10.3389/fonc.2023.1234242

J Clin Med Res. 2023 Jun;15(6):283-291. doi: 10.14740/jocmr4913. Epub 2023 Jun 29.ABSTRACTAcute kidney injury (AKI) affects increasing numbers of in-hospital patients in Central Europe and the USA, the prognosis remains poor. Although substantial progress has been achieved in the identification of molecular/cellular processes that induce and perpetuate AKI, more integrated pathophysiological perspectives are missing. Metabolomics enables the identification of low-molecular-weight (< 1.5 kD) substances from biological specimens such as certain types of fluid or tissue. The aim of the article was to review the literature on metabolic profiling in experimental AKI and to answer the question if metabolomics allows the integration of distinct pathophysiological events such as tubulopathy and microvasculopathy in ischemic and toxic AKI. The following databases were searched for references: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 1940 until 2022. The following terms were utilized: "acute kidney injury" OR "acute renal failure" OR "AKI" AND "metabolomics" OR "metabolic profiling" OR "omics" AND "ischemic" OR "toxic" OR "drug-induced" OR "sepsis" OR "LPS" OR "cisplatin" OR "cardiorenal" OR "CRS" AND "mouse" OR "mice" OR "murine" OR "rats" OR "rat". Additional search terms were "cardiac surgery", "cardiopulmonary bypass", "pig", "dog", and "swine". In total, 13 studies were identified. Five studies were related to ischemic, seven studies to toxic (lipopolysaccharide (LPS), cisplatin), and one study to heat shock-associated AKI. Only one study, related to cisplatin-induced AKI, was performed as a targeted analysis. The majority of the studies identified multiple metabolic deteriorations upon ischemia/the administration of LPS or cisplatin (e.g., amino acid, glucose, lipid metabolism). Particularly, abnormalities in the lipid homeostasis were shown under almost all experimental conditions. LPS-induced AKI most likely depends on the alterations in the tryptophan metabolism. Metabolomics studies provide a deeper understanding of pathophysiological links between distinct processes that are responsible for functional impairment/structural damage in ischemic or toxic or other types of AKI.PMID:37434774 | PMC:PMC10332883 | DOI:10.14740/jocmr4913

Front Plant Sci. 2023 Jun 26;14:1183139. doi: 10.3389/fpls.2023.1183139. eCollection 2023.ABSTRACTGastrodia elata Blume (GE), a traditional and precious Chinese medicinal material, has been approved as a functional food. However, understanding GE's nutritional properties and its molecular basis remains limited. Here, metabolomic and transcriptomic analyses were performed on young and mature tubers of G. elata.f.elata (GEEy and GEEm) and G. elata.f.glauca (GEGy and GEGm). A total of 345 metabolites were detected, including 76 different amino acids and their derivatives containing all human essential amino acids (e.g., l-(+)-lysine, l-leucine), 13 vitamins (e.g., nicotinamide, thiamine), and 34 alkaloids (e.g., spermine, choline). GEGm has higher amino acid accumulation than GEEy, GEEm and GEGy, and vitamin contents were also slightly different in all four samples. Implying that GE, especially GEGm, is a kind of excellent complementary food as amino acid nutrition provider. From assembled 21,513 transcripts (genes) based on the transcriptome, we identified many genes that encode enzymes (e.g., pfkA, bglX, tyrAa, lysA, his B, aroA), which are responsible for the biosynthesis of amino acids and enzymes (e.g., nadA, URH1, NAPRT1, punA, rsgA) that related to vitamins metabolism. A total of 16 pairs of the differentially expressed genes (DEG) and differentially accumulated metabolites (DAM) (e.g., gene-tia006709 coding GAPDH and l-(+)-arginine, and gene-tia010180 coding tyrA and l-(+)-arginine) and three DEG-DAM pairs (e.g., gene-tia015379 coding NadA and nicotinate d-ribonucleoside) show significant similar positive or negative correlation based on three, and two comparisons of GEEy vs. GEGy, GEGy vs. GEGm, GEEy vs. GEGy and GEEm vs. GEGm, which involved into amino acid biosynthesis, and nicotinate nicotinamide metabolism, respectively. These results prove that the enzyme coded by these DEG promotes (positive correlation) or inhibits (negative correlation) the biosynthesis of parallel DAM in GE. Overall, the data and corresponding analysis in this study provide new insights into the nutritional properties of GE and the related molecular basis.PMID:37434605 | PMC:PMC10331839 | DOI:10.3389/fpls.2023.1183139

Anal Methods. 2023 Jul 12. doi: 10.1039/d3ay00778b. Online ahead of print.ABSTRACTDiabetes, including its predominant form, type 2 diabetes mellitus (T2DM), has a distinctive correlation with coronary heart disease (CHD). Patients with diabetes have shown statistically higher potential risk of developing CHD complications than those without diabetes. In this study, we have conducted a metabolomic analysis of serum samples from healthy controls as well as patients with T2DM or both T2DM and CHD (CHD-T2DM). Statistical analysis of the metabolomic data revealed 611 and 420 significantly altered metabolic signatures in T2DM and CHD-T2DM patients, respectively, when compared to the healthy controls. Meanwhile, 653 metabolic features were significantly different between the CHD-T2DM and T2DM groups. Some of the metabolites at significantly different levels were identified and may serve as potential biomarkers for T2DM or CHD-T2DM. We selected three candidates, phosphocreatine (PCr), cyclic guanosine monophosphate (cGMP) and taurine for further validation among independent T2DM, CHD-T2DM and healthy control populations. These three metabolites were found to be significantly elevated in the CHD-T2DM group when compared to both T2DM and healthy control groups by the metabolomic analysis. Our results indicated that both PCr and cGMP but not taurine were successfully validated and may serve as predictive biomarkers of CHD in patients with T2DM.PMID:37434552 | DOI:10.1039/d3ay00778b

Genesis. 2023 Jul 11:e23536. doi: 10.1002/dvg.23536. Online ahead of print.ABSTRACTI completed my undergraduate education in Atatürk University, Education Faculty, Biology Department. Then pursued my graduate education at the Biology Department of Mersin University. Both my master's and PhD theses were on the biological and population genetics features of various fish species. My initial encounter with tunicates dates back to my Postdoc at Israel Oceanographic and Limnologic Research Institute (IOLR) in 2011, where I was working on a DNA barcoding project. During that time, the entire institute was actively engaged in research on tunicates, and discussions during lunchtime often revolved around this fascinating group of organisms. Prof. Rinkevich usually only spoke seriously about tunicate biology but 1 day he told me "You know Botryllus schlosseri is riding horse in Black Sea coasts of Turkiye." I was totally surprised and was trying to understand the meaning of this comment from a scientific perspective. He then showed me the picture of a B. schlosseri colony attached to a seahorse. Following several more Postdoc experiences, I began working as a Principal Investigator at Institute of Marine Sciences, Middle East Technical University (IMS-METU) in 2017. Since then, my team and I have been working on tunicate biodiversity, evolutionary biology, genomics, DNA barcoding, metabarcoding, metabolomics, whole-body regeneration (WBR) and aging related pathways.PMID:37434442 | DOI:10.1002/dvg.23536

Nutrients. 2023 Apr 23;15(9):2032. doi: 10.3390/nu15092032.ABSTRACTThe apolipoprotein E4 (APOE4) genotype is predictive of Alzheimer's disease (AD). The brain is highly enriched with the omega-3 polyunsaturated fatty acid (n3-PUFA), docosahexaenoic acid (DHA). DHA's metabolism is defective in APOE4 carriers. Flavanol intake can play a role in modulating DHA levels. However, the impact of flavanol co-supplementation with fish oil on brain DHA uptake, status and partitioning, and according to APOE genotype is currently unknown. Here, using a humanised APOE3 and APOE4 targeted replacement transgenic mouse model, the interactive influence of cocoa flavanols (FLAV) and APOE genotype on the blood and subcortical brain PUFA status following the supplementation of a high fat (HF) enriched with DHA from fish oil (FO) was investigated. DHA levels increased in the blood (p < 0.001) and brain (p = 0.001) following supplementation. Compared to APOE3, a higher red blood cell (RBC) DHA (p < 0.001) was evident in APOE4 mice following FO and FLAV supplementation. Although FO did not increase the percentage of brain DHA in APOE4, a 17.1% (p < 0.05) and 20.0% (p < 0.001) higher DHA level in the phosphatidylcholine (PC) fraction in the HF FO and HF FO FLAV groups, and a 14.5% (p < 0.05) higher DHA level in the phosphatidylethanolamine (PE) fraction in the HF FO FLAV group was evident in these animals relative to the HF controls. The addition of FLAV (+/- FO) did not significantly increase the percentage of brain DHA in the group as a whole. However, a higher brain: RBC DHA ratio was evident in APOE3 only (p < 0.05) for HF FLAV versus HF. In conclusion, our data shows only modest effects of FLAV on the brain DHA status, which is limited to APOE3.PMID:37432149 | PMC:PMC10180974 | DOI:10.3390/nu15092032

Metabolism. 2023 Jul 9:155658. doi: 10.1016/j.metabol.2023.155658. Online ahead of print.ABSTRACTBACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) has increased over the past decades. Diabetic cardiomyopathy (DCM) is the leading cause of death in T2DM patients, however, the mechanism underlying DCM remains largely unknown. Here, we aimed to investigate the role of cardiac PR-domain containing 16 (PRDM16) in T2DM.METHODS: We modeled mice with cardiac-specific deletion of Prdm16 by crossing the floxed Prdm16 mouse model with the cardiomyocyte-specific Cre transgenic mouse. The mice were continuously fed a chow diet or high-fat diet combining with streptozotocin (STZ) for 24 weeks to establish a T2DM model. DB/DB and adequate control mice were given a single intravenous injection of adeno-associated virus 9 (AAV9) carrying cardiac troponin T (cTnT) promoter-driven small hairpin RNA targeting PRDM16 (AAV9-cTnT-shPRDM16) from the retro-orbital venous plexus to knockout Prdm16 in the myocardium. There were at least 12 mice in each group. Mitochondrial morphology and function were detected using transmission electron microscopy, western blot determining the protein level of mitochondrial respiratory chain complex, mitotracker staining and Seahorse XF Cell Mito Stress Test Kit. Untargeted metabolomics analysis and RNA-seq analysis were performed to determine the molecular and metabolic changes associated with Prdm16 deficiency. BODIPY and TUNEL staining were used to detect lipid uptake and apoptosis. Co-immunoprecipitation and ChIP assays were conducted to examine the potential underlying mechanism.RESULTS: Prdm16 cardiac-specific deficiency accelerated cardiomyopathy and worsened cardiac dysfunction in mice with T2DM, aggravating mitochondrial dysfunction and apoptosis both in vivo and in vitro, while PRDM16 overexpression the deterioration. Prdm16 deficiency also caused cardiac lipid accumulation resulting in metabolic and molecular alterations in T2DM mouse models. Co-IP and luciferase assays confirmed that PRDM16 targeted and regulated the transcriptional activity, expression and interaction of PPAR-α and PGC-1α, while the overexpression of PPAR-α and PGC-1α reversed Prdm16 deficiency-induced cellular dysfunction in T2DM model. Moreover, PRDM16 regulated PPAR-α and PGC-1α and affected mitochondrial function by mainly depending on epigenetic regulation of H3K4me3.CONCLUSIONS: These findings suggest that PRDM16 exerted its protective role in myocardial lipid metabolism and mitochondrial function in T2DM in a histone lysine methyltransferase activity-dependent manner by regulating PPAR-α and PGC-1α.PMID:37433344 | DOI:10.1016/j.metabol.2023.155658

Food Chem. 2023 Jul 7;428:136805. doi: 10.1016/j.foodchem.2023.136805. Online ahead of print.ABSTRACTComprehensive 2D gas chromatography-mass spectrometry (GC × GC-MS) and non-targeted metabolomics were employed to investigate the differences in key volatile flavor substances between bacon salted with alternative salt and traditional bacon during storage. The GC × GC-MS analysis revealed that among 146 volatile compounds in both types of bacon, alcohol, aldehydes, ketones, phenols, and alkenes were the most abundant. Additionally, non-targeted metabolomics indicated that the changes in amino acids and the oxidation degradation of lipids could be the main reasons for the flavor differences among the two kinds of bacon. Furthermore, the acceptability scores of both bacon types showed a general upward trend as the storage time increased, indicating that the metabolic of substances occurring during bacon storage significantly impact its overall quality. By partially substituting sodium chloride with 22% potassium chloride and 11% calcium ascorbate, coupled with appropriate storage conditions, the quality of bacon can be improved.PMID:37433254 | DOI:10.1016/j.foodchem.2023.136805

Nat Rev Urol. 2023 Jul 11. doi: 10.1038/s41585-023-00784-5. Online ahead of print.ABSTRACTThe clinical management of advanced malignancies of the upper and lower urinary tract has been revolutionized with the advent of immune checkpoint blockers (ICBs). ICBs reinstate or bolster pre-existing immune responses while creating new T cell specificities. Immunogenic cancers, which tend to benefit more from immunotherapy than cold tumours, harbour tumour-specific neoantigens, often associated with a high tumour mutational burden, as well as CD8+ T cell infiltrates and ectopic lymphoid structures. The identification of beneficial non-self tumour antigens and natural adjuvants is the focus of current investigation. Moreover, growing evidence suggests that urinary or intestinal commensals, BCG and uropathogenic Escherichia coli influence long-term responses in patients with kidney or bladder cancer treated with ICBs. Bacteria infecting urothelium could be a prominent target for T follicular helper cells and B cells, linking innate and cognate CD8+ memory responses. In the urinary tract, commensal flora differ between healthy and tumoural mucosae. Although antibiotics can affect the prognosis of urinary tract malignancies, bacteria can have a major influence on cancer immunosurveillance. Beyond their role as biomarkers, immune responses against uropathogenic commensals could be harnessed for the design of future immunoadjuvants that can be advantageously combined with ICBs.PMID:37433926 | DOI:10.1038/s41585-023-00784-5

J Neurol. 2023 Jul 11. doi: 10.1007/s00415-023-11848-2. Online ahead of print.ABSTRACTBACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA without effective treatment. This study aimed to evaluate the comparative efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) and intermittent Theta Burst Stimulation (iTBS) in a larger cohort of SCA3 patients.METHODS: One hundred and twenty patients with SCA3 were randomly assigned to the 3 groups: 40 patients in the 1 Hz rTMS, 40 in the iTBS and 40 in the sham group. Patients underwent 10 sessions of rTMS targeting the cerebellum delivering for 5 consecutive days per week for 2 weeks (a total of 1200 pulses per session). Primary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Secondary outcomes included 10-m walking test (10MWT), nine-hole peg test (9-HPT), and PATA Rate Test (PRT). Outcome assessments were performed at baseline and on the last day of rTMS intervention.RESULTS: This study revealed that active rTMS outperformed sham in reducing the SARA and ICARS scores in SCA3 patients, but with no difference between the 1 Hz rTMS and iTBS protocol. Moreover, no significant differences were observed in SARA and ICARS scores between the mild and moderate to severe groups after the 1 Hz rTMS/iTBS therapy. Additionally, no severe adverse events were recorded in this study.CONCLUSIONS: The study concluded that both 1 Hz rTMS and iTBS interventions targeting the cerebellum are effective to improve the symptoms of ataxia in patients with SCA3.PMID:37433893 | DOI:10.1007/s00415-023-11848-2

Nat Commun. 2023 Jul 11;14(1):4113. doi: 10.1038/s41467-023-39889-1.ABSTRACTSignificant challenges remain in the computational processing of data from liquid chomratography-mass spectrometry (LC-MS)-based metabolomic experiments into metabolite features. In this study, we examine the issues of provenance and reproducibility using the current software tools. Inconsistency among the tools examined is attributed to the deficiencies of mass alignment and controls of feature quality. To address these issues, we develop the open-source software tool asari for LC-MS metabolomics data processing. Asari is designed with a set of specific algorithmic framework and data structures, and all steps are explicitly trackable. Asari compares favorably to other tools in feature detection and quantification. It offers substantial improvement in computational performance over current tools, and it is highly scalable.PMID:37433854 | DOI:10.1038/s41467-023-39889-1

Sci Rep. 2023 Jul 11;13(1):11228. doi: 10.1038/s41598-023-38357-6.ABSTRACTPhysical activity is essential in weight management, improves overall health, and mitigates obesity-related risk markers. Besides inducing changes in systemic metabolism, habitual exercise may improve gut's microbial diversity and increase the abundance of beneficial taxa in a correlated fashion. Since there is a lack of integrative omics studies on exercise and overweight populations, we studied the metabolomes and gut microbiota associated with programmed exercise in obese individuals. We measured the serum and fecal metabolites of 17 adult women with overweight during a 6-week endurance exercise program. Further, we integrated the exercise-responsive metabolites with variations in the gut microbiome and cardiorespiratory parameters. We found clear correlation with several serum and fecal metabolites, and metabolic pathways, during the exercise period in comparison to the control period, indicating increased lipid oxidation and oxidative stress. Especially, exercise caused co-occurring increase in levels of serum lyso-phosphatidylcholine moieties and fecal glycerophosphocholine. This signature was associated with several microbial metagenome pathways and the abundance of Akkermansia. The study demonstrates that, in the absence of body composition changes, aerobic exercise can induce metabolic shifts that provide substrates for beneficial gut microbiota in overweight individuals.PMID:37433843 | DOI:10.1038/s41598-023-38357-6

Cell Death Dis. 2023 Jul 12;14(7):413. doi: 10.1038/s41419-023-05957-z.ABSTRACTATPase Inhibitory Factor 1 (IF1) regulates the activity of mitochondrial ATP synthase. The expression of IF1 in differentiated human and mouse cells is highly variable. In intestinal cells, the overexpression of IF1 protects against colon inflammation. Herein, we have developed a conditional IF1-knockout mouse model in intestinal epithelium to investigate the role of IF1 in mitochondrial function and tissue homeostasis. The results show that IF1-ablated mice have increased ATP synthase/hydrolase activities, leading to profound mitochondrial dysfunction and a pro-inflammatory phenotype that impairs the permeability of the intestinal barrier compromising mouse survival upon inflammation. Deletion of IF1 prevents the formation of oligomeric assemblies of ATP synthase and alters cristae structure and the electron transport chain. Moreover, lack of IF1 promotes an intramitochondrial Ca2+ overload in vivo, minimizing the threshold to Ca2+-induced permeability transition (mPT). Removal of IF1 in cell lines also prevents the formation of oligomeric assemblies of ATP synthase, minimizing the threshold to Ca2+-induced mPT. Metabolomic analyses of mice serum and colon tissue highlight that IF1 ablation promotes the activation of de novo purine and salvage pathways. Mechanistically, lack of IF1 in cell lines increases ATP synthase/hydrolase activities and installs futile ATP hydrolysis in mitochondria, resulting in the activation of purine metabolism and in the accumulation of adenosine, both in culture medium and in mice serum. Adenosine, through ADORA2B receptors, promotes an autoimmune phenotype in mice, stressing the role of the IF1/ATP synthase axis in tissue immune responses. Overall, the results highlight that IF1 is required for ATP synthase oligomerization and that it acts as a brake to prevent ATP hydrolysis under in vivo phosphorylating conditions in intestinal cells.PMID:37433784 | DOI:10.1038/s41419-023-05957-z

Plant J. 2023 Jul 11. doi: 10.1111/tpj.16391. Online ahead of print.ABSTRACTDevelopmental transitions, occurring throughout the life cycle of plants, require precise regulation of metabolic processes to generate the energy and resources necessary for the committed growth processes. In parallel, the establishment of new cells, tissues and even organs, alongside their differentiation provoke profound changes in metabolism. It is increasingly being recognized that there is a certain degree of feedback regulation between the components and products of metabolic pathways and developmental regulators. The generation of large-scale metabolomics datasets during developmental transitions, in combination with molecular genetic approaches have helped to further our knowledge on the functional importance of metabolic regulation of development. In this perspective article, we provide insights into studies that elucidate interactions between metabolism and development at the temporal and spatial scales. We additionally discuss how this influences cell growth related processes. We also highlight how metabolic intermediates function as signaling molecules to direct plant development in response to changing internal and external conditions.PMID:37433681 | DOI:10.1111/tpj.16391

Anal Chem. 2023 Jul 11. doi: 10.1021/acs.analchem.3c00734. Online ahead of print.ABSTRACTMass spectrometry-based large-scale multi-omics research has proven to be powerful in answering biological questions; nonetheless, it faces many challenges from sample preparation to downstream data integration. To efficiently extract biomolecules of different physicochemical properties, preparation of various sample type needs specific tailoring, especially of difficult ones, such as Caenorhabditis elegans. In this study, we sought to develop a multi-omics sample preparation method starting with a single set ofC. elegans samples to save time, minimize variability, expand biomolecule coverage, and promote multi-omics integration. We investigated tissue disruption methods to effectively release biomolecules and optimized extraction strategies to achieve broader and more reproducible biomolecule coverage in proteomics, lipidomics, and metabolomics workflows. In our assessment, we also considered speediness and usability of the approaches. The developed method was validated through a study of 16C. elegans samples designed to shine light on mitochondrial unfolded protein response (UPRmt), induced by three unique stressors─knocking down electron transfer chain element cco-1, mitochondrial ribosome protein S5 mrps-5, and antibiotic treatment Doxycycline. Our findings suggested that the method achieved great coverage of proteome, lipidome, and metabolome with high reproducibility and validated that all stressors triggered UPRmt in C. elegans, although generating unique molecular signatures. Innate immune response was activated, and triglycerides were decreased under all three stressor conditions. Additionally, Doxycycline treatment elicited more distinct proteomic, lipidomic, and metabolomic response than the other two treatments. This method has been successfully used to process Saccharomyces cerevisiae (data not shown) and can likely be applied to other organisms for multi-omics research.PMID:37432911 | DOI:10.1021/acs.analchem.3c00734

J Proteome Res. 2023 Jul 11. doi: 10.1021/acs.jproteome.2c00788. Online ahead of print.ABSTRACTCommunity-acquired pneumonia (CAP) is a significant threat to human health and the leading cause of acute respiratory distress syndrome (ARDS). We aimed to reveal the metabolic profiling whether can be used for assessing CAP with or without ARDS (nARDS) and therapeutic effects on CAP patients after treatment. Urine samples were collected at the onset and recovery periods, and metabolomics was employed to identify robust biomarkers. 19 metabolites were significantly changed in the ARDS relative to nARDS, mainly involving purines and fatty acids. After treatment, 7 metabolites in the nARDS and 14 in the ARDS were found to be significantly dysregulated, including fatty acids and amino acids. In the validation cohort, we observed that the biomarker panel consisted of N2,N2-dimethylguanosine, 1-methyladenosine, 3-methylguanine, 1-methyladenosine, and uric acid exhibited better AUCs of 0.900 than pneumonia severity index and acute physiology and chronic health evaluation II (APACHE II) scores between the ARDS and nARDS. Combining L-phenylalanine, phytosphingosine, and N-acetylaspartylglutamate as biomarkers for discriminating the nARDS and ARDS patients after treatment exhibited good AUCs of 0.811 and 0.821, respectively. The metabolic pathway and defined biomarkers may serve as crucial indicators for predicting the development of ARDS in CAP patients and for assessing therapeutic effects.PMID:37432907 | DOI:10.1021/acs.jproteome.2c00788

J Nat Med. 2023 Jul 11. doi: 10.1007/s11418-023-01721-x. Online ahead of print.ABSTRACTPeony root is an important herbal drug used as an antispasmodic analgesic. To evaluate peony roots with different botanical origins, producing areas, and post-harvest processing, 1H NMR-based metabolomics analysis was employed. Five types of monoterpenoids, including albiflorin (4), paeoniflorin (6), and sulfonated paeoniflorin (25), and six other compounds, including 1,2,3,4,6-penta-O-galloyl-β-D-glucose (18), benzoic acid (21), gallic acid (22), and sucrose (26) were detected in the extracts of peony root samples. Among them, compounds 4, 6, 18, and total monoterpenoids including 21 were quantified by quantitative 1H NMR (qHNMR). Compound 25 was detected in 1H NMR spectra of sulfur-fumigated white peony root (WPR) extracts indicating that 1H NMR was a fast and effective method for identifying sulfur-fumigated WPR. The content of 26, the main factor affecting extract yield, increased significantly in peony root after low-temperature storage for one month, whereas that in WPR did not increase due to the boiling treatment after harvesting. We investigated the impact of preprocessing methods to such analysis for NMR data from commercial samples, resulting that the data matrix transformed from qHNMR spectra and normalized to internal standard were optimum for multivariate analysis. The multivariate analysis demonstrated that among commercial samples derived from P. lactiflora, peony root samples in Japanese market (PR) had high contents of 18 and 22, and red peony root (RPR) samples had high content of monoterpenoids represented by 6; and among RPR samples, those derived from P. veitchii showed higher contents of 18 and 22 than those from P. lactiflora. The 1H NMR-based metabolomics method coupled with qHNMR was useful for evaluation of peony root and would be applicable for other crude drugs.PMID:37432536 | DOI:10.1007/s11418-023-01721-x

Food Funct. 2023 Jul 11. doi: 10.1039/d3fo01551c. Online ahead of print.ABSTRACTProanthocyanidins (PAs) are one of the most commonly ingested polyphenols in the human diet, with a wide range of beneficial health effects. Remarkably, PAs have been reported to influence core and peripheral clock genes expression, and their effects may change in a time-of-day dependent manner. Therefore, the aim of this study was to investigate whether the capacity of PAs to modulate the metabolome is conditioned by the time-of-day in which these compounds are consumed in a diet- and sex-dependent manner. To do this, a grape seed proanthocyanidin extract (GSPE) was administered to female and male Fischer 344 rats at ZT0 (in the morning) and ZT12 (at night) and the GSPE administration time effect was evaluated on clock genes expression, melatonin hormone and serum metabolite levels in a healthy and obesogenic context. The results showed an administration time effect of GSPE on the metabolome in a sex and diet-dependent manner. Specifically, there was an effect on amino acid, lipid and cholate metabolite levels that correlated with the central clock genes expression. Therefore, this study shows a strong influence of sex and diet on the PAs effects on the metabolome, modulated in turn by the time-of-day.PMID:37432474 | DOI:10.1039/d3fo01551c

Nutrients. 2023 May 8;15(9):2219. doi: 10.3390/nu15092219.ABSTRACTWhile diet and nutrition are modifiable risk factors for many chronic and infectious diseases, their role in cancer prevention and control remains under investigation. The lack of clarity of some diet-cancer relationships reflects the ongoing debate about the relative contribution of genetic factors, environmental exposures, and replicative errors in stem cell division as determinate drivers of cancer risk. In addition, dietary guidance has often been based upon research assuming that the effects of diet and nutrition on carcinogenesis would be uniform across populations and for various tumor types arising in a specific organ, i.e., that one size fits all. Herein, we present a paradigm for investigating precision dietary patterns that leverages the approaches that led to successful small-molecule inhibitors in cancer treatment, namely understanding the pharmacokinetics and pharmacodynamics of small molecules for targeting carcinogenic mechanisms. We challenge the scientific community to refine the paradigm presented and to conduct proof-in-concept experiments that integrate existing knowledge (drug development, natural products, and the food metabolome) with developments in artificial intelligence to design and then test dietary patterns predicted to elicit drug-like effects on target tissues for cancer prevention and control. We refer to this precision approach as dietary oncopharmacognosy and envision it as the crosswalk between the currently defined fields of precision oncology and precision nutrition with the goal of reducing cancer deaths.PMID:37432381 | DOI:10.3390/nu15092219