Integrative physiological, transcriptome and metabolome analysis reveals the involvement of carbon and flavonoid biosynthesis in low phosphorus tolerance in cotton.

Phosphorus (P) is an essential nutrient controlling plant growth and development through the regulation of basic metabolic processes; however, the molecular details of these pathways remain largely unknown. In this study, physiological, transcriptome, and metabolome analysis were compared for two cotton genotypes with different low P tolerance under P starvation and resupply. The results showed that the glucose, fructose, sucrose, and starch contents increased by 18.2%, 20.4%, 20.2%, and 14.3% in the roots and 18.3%, 23.3%, 11.0%, and 13.6% in the shoot of Jimian169 than DES926, respectively. Moreover, the activities of enzymes related to carbon and phosphorus metabolism were higher in the roots and shoots of Jimian169 than DES926. In addition, transcriptome analysis revealed that the number of differentially expressed genes (DEGs) was higher in both roots (830) and shoots (730) under P starvation and the DEGs drastically reduced upon P resupply. The KEGG analysis indicated that DEGs were mainly enriched in phenylpropanoid biosynthesis, carbon metabolism, and photosynthesis. The metabolome analysis showed the enrichment of phenylpropanoid, organic acids and derivatives, and lipids in all the pairs at a given time point. The combined transcriptome and metabolome analysis revealed that carbon metabolism and flavonoid biosynthesis are involved in the P starvation response in cotton. Moreover, co-expression network analysis identified 3 hub genes in the roots and shoots that regulate the pathways involved in the P starvation response. This study provides the foundation for understanding the mechanisms of low P tolerance and the hub genes as a potential target for the development of low P tolerant genotypes.

Metabolic profiling in the hypothalamus of aged mice.

Metabolic abnormalities are tightly connected to the perturbation of normal brain functions, thereby causing multiple neurodegenerative diseases. The hypothalamus is the master unit that controls the whole-body energy homeostasis. Thus, altered metabolic activity in the hypothalamus could be a crucial clue to better understand the development of metabolic disorders during aging. The current study aimed to investigate the changes in hypothalamic metabolites according to the aging process using gas chromatography-mass spectrometry. We identified that multiple metabolites and neurotransmitters were effectively reduced in the hypothalamus of aged mice. In addition, we observed increased levels of genes linked to the production and utilization of monocarboxylates in the aged hypothalamus, indicating the initiation of metabolic activity to produce alternative nutrient sources. Lastly, we found a reduced number of astrocytes in the hypothalamus of aged mice, suggesting that reduced nutrient availability in the hypothalamus might be associated with the decreased activity of astrocytes during aging. Collectively, the present study suggests that the deterioration of metabolic activities in the hypothalamus might be a primary cause and/or outcome of metabolic diseases associated with the aging process.

Multi-Omic Profiling of Macrophages Treated with Phospholipids Containing Omega-3 and Omega-6 Fatty Acids Reveals Complex Immunomodulatory Adaptations at Protein, Lipid and Metabolic Levels.

In recent years, several studies have demonstrated that polyunsaturated fatty acids have strong immunomodulatory properties, altering several functions of macrophages. In the present work, we sought to provide a multi-omic approach combining the analysis of the lipidome, the proteome, and the metabolome of RAW 264.7 macrophages supplemented with phospholipids containing omega-3 (PC 18:0/22:6; ω3-PC) or omega-6 (PC 18:0/20:4; ω6-PC) fatty acids, alone and in the presence of lipopolysaccharide (LPS). Supplementation of macrophages with ω3 and ω6 phospholipids plus LPS produced a significant reprogramming of the proteome of macrophages and amplified the immune response; it also promoted the expression of anti-inflammatory proteins (e.g., pleckstrin). Supplementation with the ω3-PC and ω6-PC induced significant changes in the lipidome, with a marked increase in lipid species linked to the inflammatory response, attributed to several pro-inflammatory signalling pathways (e.g., LPCs) but also to the pro-resolving effect of inflammation (e.g., PIs). Finally, the metabolomic analysis demonstrated that supplementation with ω3-PC and ω6-PC induced the expression of several metabolites with a pronounced inflammatory and anti-inflammatory effect (e.g., succinate). Overall, our data show that supplementation of macrophages with ω3-PC and ω6-PC effectively modulates the lipidome, proteome, and metabolome of these immune cells, affecting several metabolic pathways involved in the immune response that are triggered by inflammation.

An integrated chemical characterization based on FT-NIR, GC-MS and LC-MS for the comparative metabolite profiling of wild and cultivated agarwood.

Agarwood is a well-known and precious traditional Chinese medicine, has been widely applied as drugs and spices for century. The large demand for this material has deeply stimulated the emergence of numerous cultivated products. However, it is difficult to distinguish wild agarwood from cultivated agarwood, and the chemical composition difference between them is not clear. In this study, an integrated method of Fourier transform near-infrared (FT-NIR), gas chromatography-mass spectrometry (GC-MS) and ultraperformance liquid chromatography Quadrupole-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS) was developed to explore chemical variation between wild and cultivated agarwood in combination with multivariate statistical analysis. Twenty-four wild and cultivated agarwood samples were collected from different regions. FT-NIR profiles were used to obtain the holistic metabolic characterization in combination with principal component analysis (PCA). A total of seventy-six and seventy-nine metabolites, including volatile components and 2-(2-phenethyl) chromones derivatives, were successfully identified by GC-MS and UHPLC-Q-Exactive Orbitrap/MS, respectively. Thereafter, the orthogonal-partial least square method-discriminant analysis (OPLS-DA) and variable importance in the projection (VIP) were used to screen potential characteristic chemical components (VIP > 1) in wild and cultivated agarwood, respectively. Finally, eight key chemical markers were putatively identified by two techniques to distinguish agarwood from different origins, which can be found that sesquiterpenes, aromatics, terpenoids, 2-(2-phenylethyl) chromones of the flidersia type (FTPECs) and tetrahydro-2-(2-phenylethyl) chromones (THPECs) are the most important metabolites. Summary, this research presented a comprehensive metabolomic variation between wild and cultivated agarwood on the basis of a multi-technology platform, which laid a foundation for distinguishing the two ecotypes of agarwood and was conducive to the quality control of this resource.

Cellular Bioenergetic and Metabolic Changes in Patients with Autism Spectrum Disorder.

BACKGROUND: Although Autism Spectrum Disorder (ASD) is considered a heterogeneous neurological disease in childhood, a growing body of evidence associates it with mitochondrial dysfunction explaining the observed comorbidities. INTRODUCTION: The aim of this study is to identify variations in cellular bioenergetics and metabolism dependent on mitochondrial function in ASD patients and healthy controls using Peripheral Blood Mononuclear Cells (PBMCs). We hypothesized that PBMCs may reveal the cellular pathology and provide evidence of bioenergetic and metabolic changes accompanying the disease. METHODS: PBMC from children with ASD and a control group of the same age and gender were isolated. All patients underwent an in-depth clinical evaluation. A well-characterized cohort of Bulgarian children is selected. Bioenergetic and metabolic studies of isolated PBMCs are performed with a Seahorse XFp analyzer. RESULTS: Our data show that PBMCs from patients with ASD have increased respiratory reserve capacity (by 27.5%), increased maximal respiration (by 67%) and altered adaptive response to oxidative stress induced by DMNQ. In addition, we demonstrate а strong dependence on fatty acids and impaired ability to reprogram cell metabolism. The listed characteristics are not observed in the control group. These results can contribute to a better understanding of the underlying causes of ASD, which is crucial for selecting a successful treatment. CONCLUSION: The current study, for the first time, provides a functional analysis of cell bioenergetics and metabolic changes in a group of Bulgarian patients with ASD. It reveals physiological abnormalities that do not allow mitochondria to adapt and meet the increased energetic requirements of the cell. The link between mitochondria and ASD is not yet fully understood, but this may lead to the discovery of new approaches for nutrition and therapy.

Metabolomics and health: from nutritional crops and plant-based pharmaceuticals to profiling of human biofluids.

During the past decade metabolomics has emerged as one of the fastest developing branches of "-omics" technologies. Metabolomics involves documentation, identification, and quantification of metabolites through modern analytical platforms in various biological systems. Advanced analytical tools, such as gas chromatography-mass spectrometry (GC/MS), liquid chromatography-mass spectroscopy (LC/MS), and non-destructive nuclear magnetic resonance (NMR) spectroscopy, have facilitated metabolite profiling of complex biological matrices. Metabolomics, along with transcriptomics, has an influential role in discovering connections between genetic regulation, metabolite phenotyping and biomarkers identification. Comprehensive metabolite profiling allows integration of the summarized data towards manipulation of biosynthetic pathways, determination of nutritional quality markers, improvement in crop yield, selection of desired metabolites/genes, and their heritability in modern breeding. Along with that, metabolomics is invaluable in predicting the biological activity of medicinal plants, assisting the bioactivity-guided fractionation process and bioactive leads discovery, as well as serving as a tool for quality control and authentication of commercial plant-derived natural products. Metabolomic analysis of human biofluids is implemented in clinical practice to discriminate between physiological and pathological state in humans, to aid early disease biomarker discovery and predict individual response to drug therapy. Thus, metabolomics could be utilized to preserve human health by improving the nutritional quality of crops and accelerating plant-derived bioactive leads discovery through disease diagnostics, or through increasing the therapeutic efficacy of drugs via more personalized approach. Here, we attempt to explore the potential value of metabolite profiling comprising the above-mentioned applications of metabolomics in crop improvement, medicinal plants utilization, and, in the prognosis, diagnosis and management of complex diseases.

Based on urine metabolomics to study the mechanism of Qi-deficiency affecting type 2 diabetes rats using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Qi-deficiency also called energy deficiency, which approximates to the term of sub-health in contemporary medical theory. Diabetes is similar to the symptoms of "xiaoke" in traditional Chinese medicine (TCM) which is linked with Qi-deficiency. However, the mechanism of Qi-deficiency on type 2 diabetes (T2D) has not been completely elucidated. In this study, a model on Qi-deficiency T2D rat was established by using diet with high fat and high sugar and small-dose STZ induction combined with exhaustive swimming, and the model was evaluated by pathological section, hematological index and serum biochemical parameters. Applying urine metabolomics based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to explore the underlying molecular mechanism of Qi-deficiency on T2D and 32 urinary metabolites were identified as prospective biomarkers for Qi-deficiency T2D rats. Metabolic pathway analysis indicated that synthesis and degradation of ketone bodies, starch and sucrose metabolism, phenylalanine metabolism, arachidonic acid metabolism, butanoate metabolism and TCA cycle, etc., were closely related to potential mechanisms of Qi-deficiency on T2D. The metabolomics results can provide reliable data support for complex TCM syndrome diagnosis.

Metabolome analysis revealed that soybean-Aspergillus oryzae interaction induced dynamic metabolic and daidzein prenylation changes.

Several isoflavonoids are well known for their ability to act as soybean phytoalexins. However, the overall effects of the soybean-Aspergillus oryzae interaction on metabolism remain largely unknown. The aim of this study is to reveal an overview of nutritive and metabolic changes in germinated and A. oryzae-elicited soybeans. The levels of individual nutrients were measured using the ustulation, ashing, Kjeldahl, and Folch methods. The levels of individual amino acids were measured using high-performance liquid chromatography. Low-molecular-weight compounds were measured through metabolome analysis using liquid chromatography-mass spectrometry. Although the levels of individual nutrients and amino acids were strongly influenced by the germination process, the elicitation process had little effect on the change in the contents of individual nutrients and amino acids. However, after analyzing approximately 700 metabolites using metabolome analysis, we found that the levels of many of the metabolites were strongly influenced by soybean-A. oryzae interactions. In particular, the data indicate that steroid, terpenoid, phenylpropanoid, flavonoid, and fatty acid metabolism were influenced by the elicitation process. Furthermore, we demonstrated that not the germination process but the elicitation process induced daidzein prenylation, suggesting that the soybean-A. oryzae interactions produce various phytoalexins that are valuable for health promotion and/or disease prevention.

Urinary metabolomic profiling reveals difference between two traditional Chinese medicine subtypes of coronary heart disease.

The World Health Organization has shown that coronary heart disease (CHD) is a more common cause of death than cancer. In traditional Chinese medicine (TCM), CHD is classified as a form of thoracic obstruction that can be divided in different subtypes including Qi stagnation with blood stasis (QS) and Qi deficiency with blood stasis (QD). Different treatment strategies are used based on this subtyping. Owing to the lack of scientific markers in the diagnosis of these subtypes, subjective judgments made by clinicians have limited the objective manner for utility of TCM in the treatment of CHD. Untargeted (UHPLC-QTOF-MS) and targeted (UHPLC-MS/MS) metabolomics approaches were employed to search significantly different metabolites related to the QS or QD subtypes of CHD with angina pectoris in this study. A total of 42 metabolites were obtained in the untargeted metabolomics analysis and 34 amino acids were detected in the targeted metabolomics analysis. In total, 16 metabolites were found significantly different among different groups. The results showed distinct metabolic profiles of urine samples not only between CHD patients and healthy controls, but also between the two subtypes of CHD. Pathway analysis of the significantly varied metabolites revealed that there were subtype-related differences in the activity of pathways. Therefore, urinary metabolomics can reveal the pathological changes of CHD in different subtypes, make the diagnosis of CHD in different subtypes in an objective manner and comprehensive and contribute to personalized treatment by providing scientific evidence.

Crosstalk of Multi-Omics Platforms with Plants of Therapeutic Importance.

From time immemorial, humans have exploited plants as a source of food and medicines. The World Health Organization (WHO) has recorded 21,000 plants with medicinal value out of 300,000 species available worldwide. The promising modern "multi-omics" platforms and tools have been proven as functional platforms able to endow us with comprehensive knowledge of the proteome, genome, transcriptome, and metabolome of medicinal plant systems so as to reveal the novel connected genetic (gene) pathways, proteins, regulator sequences and secondary metabolite (molecule) biosynthetic pathways of various drug and protein molecules from a variety of plants with therapeutic significance. This review paper endeavors to abridge the contemporary advancements in research areas of multi-omics and the information involved in decoding its prospective relevance to the utilization of plants with medicinal value in the present global scenario. The crosstalk of medicinal plants with genomics, transcriptomics, proteomics, and metabolomics approaches will be discussed.

Chemometric-enhanced metabolic profiling of five Pinus species using HPLC-MS/MS spectrometry: Correlation to in vitro anti-aging, anti-Alzheimer and antidiabetic activities.

Detailed metabolic profiling of needles of five Pinus species was investigated using complementary HPLC-MS/MS techniques together with supervised and unsupervised chemometric tools. This resulted in putative identification of 44 compounds belonging to flavonoids, phenolics, lignans, diterpenes and fatty acids. Unsupervised principal component analysis showed that differences were maintained across the metabolites characteristic of each Pinus species, are mainly related to di-O-p-coumaroyltrifolin, p-coumaroyl quinic acid derivative, arachidonic acid, hydroxypalmitic acid, isopimaric acid and its derivative. A supervised Partial Least Squares regression analysis was performed to correlate HPLC-MS/MS profiles with the variation observed in the in vitro anticholinesterase, antiaging and anti-diabetic potential. All investigated Pinus extracts exerted their antiaging activity via increasing telomerase and TERT levels in normal human melanocytes cells compared to the control (untreated cells). Profound inhibition activities of acetylcholinesterase and dipeptidyl peptidase-4 were also observed with P. pinea and P. canariensis extracts having comparable antidiabetic activities to sitagliptin as a standard antidiabetic drug. Our findings suggested that pine needles are a good source of phenolics and diterpenoids that have possible health promoting activities in management and alleviation of diabetic conditions and Alzheimer disease.

Comparison of chemical constituents of Bupleurum marginatum var. stenophyllum and Bupleurum chinense DC. using UHPLC-Q-TOF-MS based on a metabonomics approach.

The overall chemical composition of Bupleurum marginatum var. stenophyllum and Bupleurum chinense DC. was compared in this study. Metabolites were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Multivariate statistical analysis techniques such as principal component analysis were used to conduct metabonomics analysis and study the correlation between different components. Principal component analysis results showed a clear distinction among medicinal materials of different origins and divided them into different categories, consistent with the results of hierarchical cluster analysis. Both partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that the two materials could be distinguished clearly. Using PLS-DA and OPLS-DA combined with the S-plot and a variable importance in the projection (VIP) score >1, 24 differential metabolites were screened and identified; all of the metabolites were triterpenoid saponins. In addition, SPSS 25.0 and Metabo Analyst 4.0 were used to analyze significant differences in the relative contents of different compounds in the two materials. This study has successfully provided not only a new direction for research based on the chemical substances identified and the quality evaluation of Bupleuri Radix but also a better theoretical basis for the expansion of medicinal sources and their clinical application.

Metabolomic differences between critically Ill women and men.

Metabolism differs in women and men at homeostasis. Critically ill patients have profound dysregulation of homeostasis and metabolism. It is not clear if the metabolic response to critical illness differs in women compared to men. Such sex-specific differences in illness response would have consequences for personalized medicine. Our aim was to determine the sex-specific metabolomic response to early critical illness. We performed a post-hoc metabolomics study of the VITdAL-ICU trial where subjects received high dose vitamin D3 or placebo. Using mixed-effects modeling, we studied sex-specific changes in metabolites over time adjusted for age, Simplified Acute Physiology Score II, admission diagnosis, day 0 25-hydroxyvitamin D level, and 25-hydroxyvitamin D response to intervention. In women, multiple members of the sphingomyelin and lysophospholipid metabolite classes had significantly positive Bonferroni corrected associations over time compared to men. Further, multiple representatives of the acylcarnitine, androgenic steroid, bile acid, nucleotide and amino acid metabolite classes had significantly negative Bonferroni corrected associations over time compared to men. Gaussian graphical model analyses revealed sex-specific functional modules. Our findings show that robust and coordinated sex-specific metabolite differences exist early in critical illness.

Of Mice and Men: Impacts of Calorie Restriction on Metabolomics of the Cerebellum.

The main purpose of research in mice is to explore metabolic changes in animal models and then predict or propose potential translational benefits in humans. Although some researchers in the brain research field have mentioned that the mouse experiments results still lack the complex neuroanatomy of humans, caution is required to interpret the findings. In mice, we observed in article seventeenth of the series of the effects of graded levels of calorie restriction, metabolomic changes in the cerebellum indicated activation of hypothalamocerebellar connections driven by hunger responses. Therefore, the purpose of the current perspective is to set this latest paper into a wider context of the physiological, behavioral, and molecular changes seen in these mice and to compare and contrast them with previous human studies.

The Effects of Graded Levels of Calorie Restriction: XVI. Metabolomic Changes in the Cerebellum Indicate Activation of Hypothalamocerebellar Connections Driven by Hunger Responses.

Calorie restriction (CR) remains the most robust intervention to extend life span and improve healthspan. Though the cerebellum is more commonly associated with motor control, it has strong links with the hypothalamus and is thought to be associated with nutritional regulation and adiposity. Using a global mass spectrometry-based metabolomics approach, we identified 756 metabolites that were significantly differentially expressed in the cerebellar region of the brain of C57BL/6J mice, fed graded levels of CR (10, 20, 30, and 40 CR) compared to mice fed ad libitum for 12 hours a day. Pathway enrichment indicated changes in the pathways of adenosine and guanine (which are precursors of DNA production), aromatic amino acids (tyrosine, phenylalanine, and tryptophan) and the sulfur-containing amino acid methionine. We also saw increases in the tricarboxylic acid cycle (TCA) cycle, electron donor, and dopamine and histamine pathways. In particular, changes in l-histidine and homocarnosine correlated positively with the level of CR and food anticipatory activity and negatively with insulin and body temperature. Several metabolic and pathway changes acted against changes seen in age-associated neurodegenerative disorders, including increases in the TCA cycle and reduced l-proline. Carnitine metabolites contributed to discrimination between CR groups, which corroborates previous work in the liver and plasma. These results indicate the conservation of certain aspects of metabolism across tissues with CR. Moreover, this is the first study to indicate CR alters the cerebellar metabolome, and does so in a graded fashion, after only a short period of restriction.

Aframomum melegueta secondary metabolites exhibit polypharmacology against SARS-CoV-2 drug targets: in vitro validation of furin inhibition.

COVID-19 pandemic is currently decimating the world's most advanced technologies and largest economies and making its way to the continent of Africa. Weak medical infrastructure and over-reliance on medical aids may eventually predict worse outcomes in Africa. To reverse this trend, Africa must re-evaluate the only area with strategic advantage; phytotherapy. One of the many plants with previous antiviral potency is against RNA viruses is Aframomum melegueta. In this study, one hundred (100) A. melegueta secondary metabolites have been mined and computational evaluated for inhibition of host furin, and SARS-COV-2 targets including 3C-like proteinase (Mpro /3CLpro ), 2'-O-ribose methyltransferase (nsp16) and surface glycoprotein/ACE2 receptor interface. Silica-gel column partitioning of A. melegueta fruit/seed resulted in 6 fractions tested against furin activity. Diarylheptanoid (Letestuianin A), phenylpropanoid (4-Cinnamoyl-3-hydroxy-spiro[furan-5,2'-(1'H)-indene]-1',2,3'(2'H,5H)-trione), flavonoids (Quercetin, Apigenin and Tectochrysin) have been identified as high-binding compounds to SARS-COV-2 targets in a polypharmacology manner. Di-ethyl-ether (IC50 = 0.03 mg/L), acetone (IC50 = 1.564 mg/L), ethyl-acetate (IC50 = 0.382 mg/L) and methanol (IC50 = 0.438 mg/L) fractions demonstrated the best inhibition in kinetic assay while DEF, ASF and MEF completely inhibited furin-recognition sequence containing Ebola virus-pre-glycoprotein. In conclusion, A. melegueta and its secondary metabolites have potential for addressing the therapeutic needs of African population during the COVID-19 pandemic.

Metabolic Landscape of the Mouse Liver by Quantitative 31 P Nuclear Magnetic Resonance Analysis of the Phosphorome.

BACKGROUND AND AIMS: The liver plays a central role in all metabolic processes in the body. However, precise characterization of liver metabolism is often obscured by its inherent complexity. Phosphorylated metabolites occupy a prominent position in all anabolic and catabolic pathways. Here, we develop a 31 P nuclear magnetic resonance (NMR)-based method to study the liver "phosphorome" through the simultaneous identification and quantification of multiple hydrophilic and hydrophobic phosphorylated metabolites. APPROACH AND RESULTS: We applied this technique to define the metabolic landscape in livers from a mouse model of the rare disease disorder congenital erythropoietic porphyria (CEP) as well as two well-known murine models of nonalcoholic steatohepatitis: one genetic, methionine adenosyltransferase 1A knockout mice, and the other dietary, mice fed a high-fat choline-deficient diet. We report alterations in the concentrations of phosphorylated metabolites that are readouts of the balance between glycolysis, gluconeogenesis, the pentose phosphate pathway, the tricarboxylic acid cycle, and oxidative phosphorylation and of phospholipid metabolism and apoptosis. Moreover, these changes correlate with the main histological features: steatosis, apoptosis, iron deposits, and fibrosis. Strikingly, treatment with the repurposed drug ciclopirox improves the phosphoromic profile of CEP mice, an effect that was mirrored by the normalization of liver histology. CONCLUSIONS: In conclusion, these findings indicate that NMR-based phosphoromics may be used to unravel metabolic phenotypes of liver injury and to identify the mechanism of drug action.

Altered metabolic profiles and biomarkers associated with astragaloside IV-mediated protection against cisplatin-induced acute kidney injury in rats: An HPLC-TOF/MS-based untargeted metabolomics study.

Cisplatin (CDDP)-induced acute kidney injury (AKI) limits the therapeutic use of CDDP, which urgently needs to be addressed. Our previous study demonstrated that astragaloside IV (AS IV), an active compound of the traditional Chinese herb Astragalus membranaceus, alleviated CDDP-induced AKI. To explore the mechanism, we performed a metabolomics study to explore the altered metabolic pathways and screen for sensitive biomarkers. Twenty-four rats were randomly divided into three groups, which were treated with vehicle solutions (Control), intraperitoneally injected CDDP, and intraperitoneally injected CDDP plus oral AS IV, respectively. Metabolic profiles of serum, urine, and kidney samples were analyzed by high-performance liquid chromatography-time of flight mass spectrometry. There were 38 key metabolites in the urine samples, 20 in the serum samples, and 16 in the kidney samples that were significantly altered due to AS IV-mediated protection against CDDP-induced AKI relative to CDDP-only treatment. CDDP + AS IV co-treatment significantly altered two pathways in the blood (biosynthesis of unsaturated fatty acids and alanine, aspartate, and glutamate metabolism), five pathways in the urine (phenylalanine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; arginine biosynthesis; arginine and proline metabolism; and histidine metabolism), and five pathways in the kidneys (glutathione metabolism; alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; and D-glutamine and D-glutamate metabolism). The metabolic pathways were mainly associated with improvements in inflammatory responses, oxidative stress, and energy metabolism. Adrenic acid in serum and L-histidine and L-methionine in urine were identified as sensitive biomarkers. This study provides new insights to understand the mechanism of AS IV-mediated protection against CDDP-induced AKI and has identified three candidate biomarkers to evaluate preventative treatment and assess therapeutic effectiveness.

Antioxidant Function and Metabolomics Study in Mice after Dietary Supplementation with Methionine.

The antioxidant function and metabolic profiles in mice after dietary supplementation with methionine were investigated. The results showed that methionine supplementation enhanced liver GSH-Px activity and upregulated Gpx1 expression in the liver and SOD1 and Gpx4 expressions in the jejunum. Nrf2/Keap1 is involved in oxidative stress, and the western blotting data exhibited that dietary methionine markedly increased Keap1 abundance, while failed to influence the Nrf2 signal. Metabolomics investigation showed that methionine administration increased 2-hydroxypyridine, salicin, and asparagine and reduced D-Talose, maltose, aminoisobutyric acid, and inosine 5'-monophosphate in the liver, which are widely reported to involve in oxidative stress, lipid metabolism, and nucleotides generation. In conclusion, our study provides insights into antioxidant function and liver metabolic profiles in response to dietary supplementation with methionine.

Microbiota Supplementation with Bifidobacterium and Lactobacillus Modifies the Preterm Infant Gut Microbiota and Metabolome: An Observational Study.

Supplementation with members of the early-life microbiota as "probiotics" is increasingly used in attempts to beneficially manipulate the preterm infant gut microbiota. We performed a large observational longitudinal study comprising two preterm groups: 101 infants orally supplemented with Bifidobacterium and Lactobacillus (Bif/Lacto) and 133 infants non-supplemented (control) matched by age, sex, and delivery method. 16S rRNA gene profiling on fecal samples (n = 592) showed a predominance of Bifidobacterium and a lower abundance of pathobionts in the Bif/Lacto group. Metabolomic analysis showed higher fecal acetate and lactate and a lower fecal pH in the Bif/Lacto group compared to the control group. Fecal acetate positively correlated with relative abundance of Bifidobacterium, consistent with the ability of the supplemented Bifidobacterium strain to metabolize human milk oligosaccharides into acetate. This study demonstrates that microbiota supplementation is associated with a Bifidobacterium-dominated preterm microbiota and gastrointestinal environment more closely resembling that of full-term infants.