PubMed

World J Gastroenterol. 2022 Oct 21;28(39):5764-5783. doi: 10.3748/wjg.v28.i39.5764.ABSTRACTBACKGROUND: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are two unexplained immune diseases. The golden standard for diagnosis of these diseases requires a liver biopsy. Liver biopsy is not widely accepted by patients because of its invasive nature, and atypical liver histology can confuse diagnosis. In view of the lack of effective diagnostic markers for PBC and AIH, combined with the increasingly mature metabolomics technologies, including full-contour metabolomics and target.AIM: To determine non-invasive, reliable, and sensitive biochemical markers for the differential diagnosis of PBC and AIH.METHODS: Serum samples from 54 patients with PBC, 26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry serum metabolomics. The metabolites and metabolic pathways were identified, and the metabolic changes, metabolic pathways and inter-group differences between PBC and AIH were analyzed. Fifteen kinds of target metabolites of bile acids (BAs) were quantitatively analyzed by SRM, and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis.RESULTS: We found the changes in the levels of amino acids, BAs, organic acids, phospholipids, choline, sugar, and sugar alcohols in patients with PBC and AIH. Furthermore, the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid, lithocholic acid (LCA), taurolithocholic acid (TLCA), and LCA + TLCA in the PBC group compared with those in the AIH group. The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases. The levels of glycochenodeoxycholic acid, glycochenodeoxycholic sulfate, and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class, which was correlated with the severity of disease.CONCLUSION: The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.PMID:36338890 | PMC:PMC9627419 | DOI:10.3748/wjg.v28.i39.5764

Hortic Res. 2022 Aug 25;9:uhac189. doi: 10.1093/hr/uhac189. eCollection 2022.ABSTRACTThe Actinidia (kiwifruit) is an emerging fruit plant that is severely affected by salt stress in northern China. Plants have evolved several signaling network mechanisms to cope with the detrimental effects of salt stress. To date, no reported work is available on metabolic and molecular mechanisms involved in kiwifruit salt tolerance. Therefore, the present study aims to decipher intricate adaptive responses of two contrasting salt tolerance kiwifruit species Actinidia valvata [ZMH (an important genotype), hereafter referred to as R] and Actinidia deliciosa ['Hayward' (an important green-fleshed cultivar), hereafter referred to as H] under 0.4% (w/w) salt stress for time courses of 0, 12, 24, and 72 hours (hereafter refered to as h) by combined transcriptome and metabolome analysis. Data revealed that kiwifruit displayed specific enrichment of differentially expressed genes (DEGs) under salt stress. Interestingly, roots of R plants showed a differential expression pattern for up-regulated genes. The KEGG pathway analysis revealed the enrichment of DEGs related to plant hormone signal transduction, glycine metabolism, serine and threonine metabolism, glutathione metabolism, and pyruvate metabolism in the roots of R under salt stress. The WGCNA resulted in the identification of five candidate genes related to glycine betaine (GB), pyruvate, total soluble sugars (TSS), and glutathione biosynthesis in kiwifruit. An integrated study of transcriptome and metabolome identified several genes encoding metabolites involved in pyruvate metabolism. Furthermore, several genes encoding transcription factors were mainly induced in R under salt stress. Functional validation results for overexpression of a candidate gene betaine aldehyde dehydrogenase (AvBADH, R_transcript_80484) from R showed significantly improved salt tolerance in Arabidopsis thaliana (hereafter referred to as At) and Actinidia chinensis ['Hongyang' (an important red-fleshed cultivar), hereafter referred to as Ac] transgenic plants than in WT plants. All in all, salt stress tolerance in kiwifruit roots is an intricate regulatory mechanism that consists of several genes encoding specific metabolites.PMID:36338850 | PMC:PMC9630968 | DOI:10.1093/hr/uhac189

Front Physiol. 2022 Oct 20;13:1037758. doi: 10.3389/fphys.2022.1037758. eCollection 2022.ABSTRACTMacropinocytosis is a unique type of endocytosis accompanied by membrane ruffle formation. Closure of membrane ruffles leads to the uptake of large volumes of fluid phase and, subsequently, the formation of large vacuoles termed macropinosomes. Immune cells, such as dendritic cells, T cells, and macrophages, endocytose the surrounding amino acids and pathogens via macropinocytosis either constitutively or in a stimulus-dependent fashion. This process is critical for cell migration, mammalian target of rapamycin complex 1 (mTORC1) activation, and antigen presentation. Large vacuoles are fragmented into tubules and smaller vesicles during the progression and maturation of macropinosomes in immune cells. This process is called "macropinosome resolution" and requires osmotically driven shrinkage of macropinosomes, which is controlled by ion channels present in them. The crenation of membranes on shrunken macropinosomes is recognized by curvature-sensing proteins and results in intracellular membrane trafficking. In this mini review, we highlight the recent progress in research on macropinosome resolution in macrophages, with a focus on ion channels (TPC1/2 for Na+ and TMEM206 for Cl-) that is required for macropinosome resolution. We also discuss the potential contribution of membrane lipids to this process.PMID:36338503 | PMC:PMC9630563 | DOI:10.3389/fphys.2022.1037758

Front Physiol. 2022 Oct 21;13:989105. doi: 10.3389/fphys.2022.989105. eCollection 2022.ABSTRACTCoronary heart disease (CHD) is caused by coronary atherosclerosis and has a high morbidity and mortality rate worldwide. There are challenges in both early screening and treatment of CHD. The appearance and development of CHD is a complex metabolic disorder process. Therefore, to search for new biomarkers of CHD, we analyzed the peripheral blood metabolome in patients with CHD. In the study, a plasma metabolite, 4'-Phosphopantetheine (4-PPanSH), which was discovered by HPLC-MS/MS, as peripheral blood 4-PPanSH decreases, the degree of coronary blockage gradually aggravates. In addition, the 4-PPanSH supplement limited atherosclerotic plaque formation and endothelial injury in mice. Further, in vascular endothelial cells, 4-PPanSH effectively inhibited ROS generation and ox-LDL accumulation. In summary, 4-PPanSH was associated with the degree of coronary stenosis, and the 4-PPanSH supplement reduced atherosclerotic plaque generation, which could be associated with 4-PPanSH acting as a potent antioxidant that inhibits ROS generation and alleviates vascular endothelial injury.PMID:36338497 | PMC:PMC9634529 | DOI:10.3389/fphys.2022.989105

Breathe (Sheff). 2022 Mar;18(1):210161. doi: 10.1183/20734735.0161-2021. Epub 2022 Apr 5.ABSTRACTThe respiratory microbiome and its impact in health and disease is now well characterised. With the development of next-generation sequencing and the use of other techniques such as metabolomics, the functional impact of microorganisms in different host environments can be elucidated. It is now clear that the respiratory microbiome plays an important role in respiratory disease. In some diseases, such as bronchiectasis, examination of the microbiome can even be used to identify patients at higher risk of poor outcomes. Furthermore, the microbiome can aid in phenotyping. Finally, development of multi-omic analysis has revealed interactions between the host and microbiome in some conditions. This review, although not exhaustive, aims to outline how the microbiome is investigated, the healthy respiratory microbiome and its role in respiratory disease.EDUCATIONAL AIMS: To define the respiratory microbiome and describe its analysis.To outline the respiratory microbiome in health and disease.To describe future directions for microbiome research.PMID:36338247 | PMC:PMC9584600 | DOI:10.1183/20734735.0161-2021

Front Microbiol. 2022 Oct 20;13:984654. doi: 10.3389/fmicb.2022.984654. eCollection 2022.ABSTRACTCecal microflora plays a key role in the production performance and immune function of chickens. White Leghorn (WL) is a well-known commercial layer line chicken with high egg production rate. In contrast, Silky Fowl (SF), a Chinese native chicken variety, has a low egg production rate, but good immune performance. This study analyzed the composition of cecal microbiota, metabolism, and gene expression in intestinal tissue of these varieties and the correlations among them. Significant differences were observed in the cecal microbes: Bacteroides was significantly enriched in WL, whereas Veillonellaceae and Parabacteroides were significantly enriched in SF. Carbohydrate biosynthesis and metabolism pathways were significantly upregulated in WL cecum, which might provide more energy to the host, leading to persistently high levels of egg production. The higher Parabacteroides abundance in SF increased volicitin content, enhanced α-linolenic acid metabolism, and significantly negatively correlated with metabolites of propanoate metabolism and carbohydrate metabolism. Genes related to lipid metabolism, immunity, and melanogenesis were significantly upregulated in the SF cecum, regulating lipid metabolism, and participating in the immune response, while genes related to glucose metabolism and bile acid metabolism were expressed at higher levels in WL, benefiting energy support. This study provided a mechanism for intestinal microorganisms and metabolic pathways to regulate chicken egg-laying performance and immunity.PMID:36338096 | PMC:PMC9633115 | DOI:10.3389/fmicb.2022.984654

Front Microbiol. 2022 Oct 19;13:1017147. doi: 10.3389/fmicb.2022.1017147. eCollection 2022.ABSTRACTOBJECTIVE: The purpose of this study was to investigate the specific alterations in gut microbiome and serum metabolome and their interactions in patients with polycystic ovary syndrome (PCOS).METHODS: The stool samples from 32 PCOS patients and 18 healthy controls underwent the intestinal microbiome analysis using shotgun metagenomics sequencing approach. Serum metabolome was analyzed by ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. An integrative network by combining metagenomics and metabolomics datasets was constructed to explore the possible interactions between gut microbiota and circulating metabolites in PCOS, which was further assessed by fecal microbiota transplantation (FMT) in a rat trial.RESULTS: Fecal metagenomics identified 64 microbial strains significantly differing between PCOS and healthy subjects, half of which were enriched in patients. These changed species showed an ability to perturb host metabolic homeostasis (including insulin resistance and fatty acid metabolism) and inflammatory levels (such as PI3K/Akt/mTOR signaling pathways) by expressing sterol regulatory element-binding transcription factor-1, serine/threonine-protein kinase mTOR, and 3-oxoacyl-[acyl-cattier-protein] synthase III, possibly suggesting the potential mechanisms of gut microbiota underlying PCOS. By integrating multi-omics datasets, the panel comprising seven strains (Achromobacter xylosoxidans, Pseudomonas sp. M1, Aquitalea pelogenes, Porphyrobacter sp. HL-46, Vibrio fortis, Leisingera sp. ANG-Vp, and Sinorhizobium meliloti) and three metabolites [ganglioside GM3 (d18:0/16:0), ceramide (d16:2/22:0), and 3Z,6Z,9Z-pentacosatriene] showed the highest predictivity of PCOS (AUC: 1.0) with sensitivity of 0.97 and specificity of 1.0. Moreover, the intestinal microbiome modifications by FMT were demonstrated to regulate PCOS phenotypes including metabolic variables and reproductive hormones.CONCLUSION: Our findings revealed key microbial and metabolite features and their interactions underlying PCOS by integrating multi-omics approaches, which may provide novel insights into discovering clinical diagnostic biomarkers and developing efficient therapeutic strategies for PCOS.PMID:36338055 | PMC:PMC9627625 | DOI:10.3389/fmicb.2022.1017147

Front Nutr. 2022 Oct 20;9:1025511. doi: 10.3389/fnut.2022.1025511. eCollection 2022.ABSTRACTThe gut microbiota and related metabolites are positively regulated by soluble dietary fiber (SDF). In this study, we explored the effects of SDF from pear pomace (PP) on the regulation of gut microbiota and metabolism in high-fat-diet-fed (HFD-fed) C57BL/6J male mice. The results showed that PP-SDF was able to maintain the HFD disrupted gut microbiota diversity with a significant increase in Lachnospiraceae_UCG-006, Akkermansia, and Bifidobacterium spp. The negative effects of high-fat diet were ameliorated by PP-SDF by regulating lipid metabolisms with a significant increase in metabolites like isobutyryl carnitine and dioscoretine. Correlation analysis revealed that gut microbiota, such as Akkermansia and Lachnospiraceae_UCG-006 in the PP-SDF intervention groups had strong positive correlations with isobutyryl carnitine and dioscoretin. These findings demonstrated that PP-SDF interfered with the host's gut microbiota and related metabolites to reduce the negative effects caused by a high-fat diet.PMID:36337664 | PMC:PMC9633104 | DOI:10.3389/fnut.2022.1025511

Front Nutr. 2022 Oct 19;9:984094. doi: 10.3389/fnut.2022.984094. eCollection 2022.ABSTRACTYeasts are reported to be rich in folates, a group of vitamers known to be involved in several biosynthetic reactions such as methylation reactions, oxidation and reduction processes, and nucleotide synthesis. Not being able to synthesize folates, humans rely on external folate supply. Here, we show the application of LC/MS-MS methods using SIDA (stable isotope dilution analysis) assays for the quantitative analysis of different folate mono- and polyglutamates during growth of Saccharomyces cerevisiae. Molecular networking (MN) was applied for detailed analysis of further folate metabolites. Highest folate contents of 13,120 μg/100 g were observed after 20 h of cultivation. The main vitamers 5-CH3-H4folate and H4folate decreased during cultivation, while 5-CHO-H4folate increased during cultivation. The hexa- and heptaglutamate of 5-CH3-H4folate accounted for >96% of the total 5-CH3-H4folate content. A shift of the major polyglutamate from hexa- to heptaglutamate was observed after 29 h. MN unraveled two groups of novel folates which could be assigned to a potentially existing C2-metabolism in yeast. In detail, 5,10-ethenyl-tetrahydrofolate and a further CO-substituted 5-CH3-H4folate were identified as hexa- and heptaglutamates. The latter was neither identified as 5-acetyl-tetrahydrofolate nor as EthylFox, the oxidation product of 5-ethyl-tetrahydrofolate. The structure needs to be elucidated in future studies.PMID:36337654 | PMC:PMC9626864 | DOI:10.3389/fnut.2022.984094

Front Nutr. 2022 Oct 13;9:934294. doi: 10.3389/fnut.2022.934294. eCollection 2022.ABSTRACTObesity and atherosclerosis are the most prevalent metabolic diseases. ApoE-/- and ob/ob mice are widely used as models to study the pathogenesis of these diseases. However, how gut microbes, gut bacteriophages, and metabolites change in these two disease models is unclear. Here, we used wild-type C57BL/6J (Wt) mice as normal controls to analyze the intestinal archaea, bacteria, bacteriophages, and microbial metabolites of ob/ob and ApoE-/- mice through metagenomics and metabolomics. Analysis of the intestinal archaea showed that the abundances of Methanobrevibacter and Halolamina were significantly increased and decreased, respectively, in the ob/ob group compared with those in the Wt and ApoE-/- groups (p < 0.05). Compared with those of the Wt group, the relative abundances of the bacterial genera Enterorhabdus, Alistipes, Bacteroides, Prevotella, Rikenella, Barnesiella, Porphyromonas, Riemerella, and Bifidobacterium were significantly decreased (p < 0.05) in the ob/ob mice, and the relative abundance of Akkermansia was significantly decreased in the ApoE-/- group. The relative abundances of A. muciniphila and L. murinus were significantly decreased and increased, respectively, in the ob/ob and ApoE-/- groups compared with those of the Wt group (p < 0.05). Lactobacillus_ prophage_ Lj965 and Lactobacillus _ prophage _ Lj771 were significantly more abundant in the ob/ob mice than in the Wt mice. Analysis of the aminoacyl-tRNA biosynthesis metabolic pathway revealed that the enriched compounds of phenylalanine, glutamine, glycine, serine, methionine, valine, alanine, lysine, isoleucine, leucine, threonine, tryptophan, and tyrosine were downregulated in the ApoE-/- mice compared with those of the ob/ob mice. Aminoacyl-tRNA synthetases are considered manifestations of metabolic diseases and are closely associated with obesity, atherosclerosis, and type 2 diabetes. These data offer new insight regarding possible causes of these diseases and provide a foundation for studying the regulation of various food nutrients in metabolic disease models.PMID:36337626 | PMC:PMC9634818 | DOI:10.3389/fnut.2022.934294

Front Nutr. 2022 Oct 20;9:930414. doi: 10.3389/fnut.2022.930414. eCollection 2022.ABSTRACTBACKGROUND: Resistant starch (RS) type 4 (RS4) is a type of RS, a class of non-digestible prebiotic dietary fibers with a range of demonstrated metabolic health benefits to the host. On the other hand, bile acids (BA) have recently emerged as an important class of metabolic function mediators that involve host-microbiota interactions. RS consumption alters fecal and cecal BA in humans and rodents, respectively. The effect of RS intake on circulating BA concentrations remains unexplored in humans.METHODS AND RESULTS: Using available plasma and stool samples from our previously reported double-blind, controlled, 2-arm crossover nutrition intervention trial (Clinicaltrials.gov: NCT01887964), a liquid-chromatography/mass-spectrometry-based targeted multiple reaction monitoring, and absolute quantifications, we assessed BA changes after 12 weeks of an average 12 g/day RS4-intake. Stool BA concentrations were lower post RS4 compared to the control, the two groups consuming similar macronutrients (n = 14/group). Partial least squares-discriminant analysis revealed distinct BA signatures in stool and plasma post interventions. The increased circulating BA concentrations were further investigated using linear mixed-effect modeling that controlled for potential confounders. A higher plasma abundance of several BA species post RS4 was observed (fold increase compared to control in parenthesis): taurocholic acid (1.92), taurodeoxycholic acid (1.60), glycochenodeoxycholic acid (1.58), glycodeoxycholic acid (1.79), and deoxycholic acid (1.77) (all, p < 0.05). Distinct microbiome ortholog-signatures were observed between RS4 and control groups (95% CI), derived using the Piphillin function-prediction algorithm and principal component analysis (PCA) of pre-existing 16S rRNA gene sequences. Association of Bifidobacterium adolescentis with secondary BA such as, deoxycholic acid (rho = 0.55, p = 0.05), glycodeoxycholic acid (rho = 0.65, p = 0.02), and taurodeoxycholic acid (rho = 0.56, p = 0.04) were observed in the RS4-group, but not in the control group (all, p > 0.05).CONCLUSION: Our observations indicate a previously unknown in humans- RS4-associated systemic alteration of microbiota-derived secondary BA. Follow-up investigations of BA biosynthesis in the context of RS4 may provide molecular targets to understand and manipulate microbiome-host interactions.PMID:36337613 | PMC:PMC9631925 | DOI:10.3389/fnut.2022.930414

Biomed Chromatogr. 2022 Nov 6:e5523. doi: 10.1002/bmc.5523. Online ahead of print.ABSTRACTOccupational chronic cadmium poisoning (OCCP) can cause irreversible organ damage. Currently, no effective treatment is available for OCCP, and effective and sensitive biomarkers for treatment evaluation are still lacking. In this study, metabolomics techniques were used to analyze changes in endogenous metabolites in the urine of patients with OCCP after 15 years of treatment. Thirty urine samples from female patients with OCCP and healthy female controls (n = 15 per group) were assessed using gas chromatography-time-of-flight mass spectrometry and ultra-high-performance liquid chromatography-Q-Exactive mass spectrometry. The OCCP group had higher concentrations of blood urea nitrogen and urinary cadmium but near-normal urinary concentrations of β2 -microglobulin and retinol-binding protein. Compared to the control group, the OCCP group had 66 significantly different metabolites with a variable importance in projection score greater than 1 and P < 0.05. These differential metabolites were involved in various metabolic pathways, such as creatine metabolism, nicotinate and nicotinamide metabolism, the pentose phosphate pathway, d-glutamine and d-glutamate metabolism, and amino acid metabolism. Compared to the control group, the OCCP group had significantly higher urinary concentrations of creatine, glutamic acid, quinolinic acid, and nicotinic acid. In a receiver operator characteristic analysis, the area under the curve (AUC) of creatine was higher than the AUCs for glutamic acid, quinolinic acid, and nicotinic acid, indicating that urinary concentrations of creatine could be used as a sensitive biomarker for the diagnosis and prognosis of OCCP and for monitoring its treatment.PMID:36336973 | DOI:10.1002/bmc.5523

Front Biosci (Landmark Ed). 2022 Oct 28;27(10):294. doi: 10.31083/j.fbl2710294.ABSTRACTEnvironmental toxicogenomics aims to collect, analyze and interpret data on changes in gene expression and protein activity resulting from exposure to toxic substances using high-performance omics technologies. Molecular profiling methods such as genomics, transcriptomics, proteomics, metabolomics, and bioinformatics techniques, permit the simultaneous analysis of a multitude of gene variants in an organism exposed to toxic agents to search for genes prone to damage, detect patterns and mechanisms of toxicity, and identify specific gene expression profiles that can provide biomarkers of exposure and risk. Compared to previous approaches to measuring molecular changes caused by toxicants, toxicogenomic technologies can improve environmental risk assessment while reducing animal studies. We discuss the prospects and limitations of converting omic datasets into valuable information, focusing on assessing the risks of mixed toxic substances to the environment and human health.PMID:36336867 | DOI:10.31083/j.fbl2710294

New Phytol. 2022 Nov 6. doi: 10.1111/nph.18602. Online ahead of print.ABSTRACTAuxin phytohormone has a role in most aspects of the life of a land plant and is found even in ancient plants such as single-cell green algae. Auxin's ubiquitous but specific effects have been mainly explained by the extraordinary ability of plants to interpret spatiotemporal patterns of auxin concentrations via the regulation of gene transcription. This is thought to be achieved through the combinatorial effects of two families of nuclear co-receptor proteins, i.e., the TIR1/AFBs and AUX/IAAs. Recent evidence has suggested transcription-independent roles of TIR1/AFBs localized outside the nucleus and TMK-based auxin signaling occurring in the plasma membrane. Furthermore, emerging evidence supports a coordinated action of the intra- and extra-nuclear auxin signaling pathways to regulate specific auxin responses. Here, we highlight how auxin signaling acts inside and outside the nucleus for the regulation of growth and morphogenesis and propose that the future direction of auxin biology lies in the elucidation of a new collaborative paradigm of intra- and extra-nuclear auxin signaling.PMID:36336825 | DOI:10.1111/nph.18602

New Phytol. 2022 Nov 6. doi: 10.1111/nph.18601. Online ahead of print.ABSTRACTPlants produce a wide diversity of metabolites. Yet our understanding of how shifts in plant metabolites as a response to climate change feedback on ecosystem processes remains scarce. Here, we test to what extent climate warming shifts the seasonality of metabolites produced by Sphagnum mosses, and what are the consequences of these shifts for peatland C uptake. We used a reciprocal transplant experiment along a climate gradient in Europe to simulate climate change. We evaluated the responses of primary and secondary metabolites in five Sphagnum species and related their responses to gross ecosystem productivity (GEP). When transplanted to a warmer climate, Sphagnum species showed consistent responses to warming, with an up-regulation of either their primary or secondary metabolites according to seasons. Moreover, these shifts were correlated to changes in GEP, especially in spring and autumn. Our results indicate that the Sphagnum metabolome is very plastic and sensitive to warming. We also show that warming-induced changes in the seasonality of Sphagnum metabolites have consequences on peatland GEP. Our findings demonstrate the capacity for plant metabolic plasticity to impact ecosystem C processes and reveal a further mechanism through which Sphagnum could shape peatland responses to climate change.PMID:36336780 | DOI:10.1111/nph.18601

Comp Biochem Physiol C Toxicol Pharmacol. 2022 Nov 3:109501. doi: 10.1016/j.cbpc.2022.109501. Online ahead of print.ABSTRACTDepression is a common mental disorder that can adversely affect psychosocial function and quality of life. However, the exact aetiology and pathogenesis of depression are still unclear. Stress plays a major role in the pathogenesis of depression. The use of currently prescribed antidepressants has many side effects. Centella asiatica (C. asiatica) has shown promising antidepressant activity in rodent models. Here, we developed a reserpine-induced zebrafish stress-like model and performed behavioural analysis, cortisol measurement and 1H-Nuclear Magnetic Resonance (1H NMR) spectroscopy-based metabolomics analysis to test the anti-stress activity of ethanolic extract of C. asiatica (RECA). A significant increase in total distance travelled (F(8,8) = 8.905, p = 0.0054) and a reduction in freezing duration (F(9, 9) = 10.38, p = 0.0018) were found in the open field test (OFT). Asiaticoside, one of tested C.asiatica's triterpenoid gives a significant increase in contact duration (F(5,5) = 142.3, (p = 0.0330) at 2.5 mg/kg). Eight biomarkers were found, i.e. ß-hydroxyisovaleric acid, leucine, threonine, scylloinositol, lactate, betaine, valine, choline and l-fucose, to be responsible for the class separation between stress and RECA-treated groups. Metabolic pathway alteration in zebrafish brain upon treatment with RECA was identified as valine, leucine and isoleucine biosynthesis, while alanine, aspartate, glutamate and glycerophospholipid metabolism was involved after fluoxetine treatment.PMID:36336330 | DOI:10.1016/j.cbpc.2022.109501

Int J Cardiol. 2022 Nov 3:S0167-5273(22)01688-6. doi: 10.1016/j.ijcard.2022.11.001. Online ahead of print.NO ABSTRACTPMID:36336191 | DOI:10.1016/j.ijcard.2022.11.001

J Biotechnol. 2022 Nov 3:S0168-1656(22)00264-4. doi: 10.1016/j.jbiotec.2022.11.002. Online ahead of print.ABSTRACTLactobacillus rhamnosus GG (LGG) is one of the most widely used probiotics because of its health benefits and safety. Fucose is among the most abundant hexoses in the human intestine, and LGG consumes fucose to produce energy or proliferate. However, no study has elucidated the metabolism by which LGG metabolizes fucose to produce energy, biomass, and extracellular metabolites. We used metabolomics and flux balance analysis to elucidate these mechanisms and highlight how they might affect the host. We found three different metabolic flux modes by which LGG anaerobically metabolizes fucose to produce energy and biomass. These metabolic flux modes differ from homolactic or heterolactic fermentation and account for the production of lactic acid, 1,2-propanediol, acetic acid, formic acid, and carbon dioxide as a result of fucose metabolism in LGG. We also used gas chromatography/time-of-flight mass spectrometry to identify a variety of short-chain fatty acids and organic acids secreted during fucose metabolism by LGG. Our study is the first to elucidate the unique fucose metabolism of LGG in anaerobic condition.PMID:36336085 | DOI:10.1016/j.jbiotec.2022.11.002

Bioorg Chem. 2022 Oct 29;130:106229. doi: 10.1016/j.bioorg.2022.106229. Online ahead of print.ABSTRACTLiver cancer has characteristics of high morbidity, high mortality, and poor prognosis. Metabolic reprogramming is a prominent characteristic of tumors and plays a key role in promoting tumorigenesis. The metabolic process of liver cancer cells has undergone many significant changes including abnormal active glycolysis, enhanced de novo synthesis of fatty acids, and hyperactive metabolism of amino acids and nucleotides. Targeting metabolic reprogramming through regulation of anomalously expressed key metabolic enzymes and signaling molecules is considered to be an important strategy for liver cancer treatment. Multi-omics association analyses currently facilitate precise diagnosis, personalized clinical therapy, and revelation of mechanisms of drug action. Cinobufagin, as the major anti-tumor active ingredient of Chansu, the famous chinese medicine used in clinic for cancer treatment, has been reported to exert anticancer effects through many different kinds of mechanisms, but the effects of cinobufagin on metabolic reprogramming of cancer cells still remain unclear. In our study, we identify that cinobufagin exhibits anti-hepatoma effects through interfering with metabolic reprogramming (lipid, amino acid, carbohydrate, and nucleotide metabolism) based on integrated transcriptomics and metabolomics analyses. Furthermore, the results of integrated multi-omics analyses enrich various core regulatory mechanisms of anti-tumor effects of cinobufagin which are associated with metabolic pathway. In addition, some verifications of the enriched mechanisms related to intervention of lipid and carbohydrate metabolism in response to cinobufagin are also performed. This work will promote the innovation of the research model of TCM, and lay a solid theoretical foundation for the clinical application of cinobufagin and Chansu.PMID:36335648 | DOI:10.1016/j.bioorg.2022.106229

J Transl Med. 2022 Nov 5;20(1):510. doi: 10.1186/s12967-022-03717-9.ABSTRACTBACKGROUND: Diabetic kidney disease (DKD) is among the most important causes for chronic kidney disease. Anthocyanins (ANT) are polyphenolic compounds present in various food and play an important role in ameliorating hyperglycemia and insulin sensitivity. However, the effects of ANT in DKD are still poorly understood. This study aimed to investigate the effect of ANT (cyanidin-3-O-glucoside [C3G]) on the renal function of DKD, and whether the anti-DKD effect of ANT is related to metabolic pathways.METHODS: To explore the role of ANT in DKD, we performed the examination of blood glucose, renal function, and histopathology. As for the mechanism, we designed the label-free quantification proteomics and nontargeted metabolomics analysis for kidney and serum. Subsequently, we revealed the anti-DKD effect of ANT through the bioinformatic analysis.RESULTS: We showed that the fasting blood glucose level (- 6.1 mmol/L, P = 0.037), perimeter of glomerular lesions (- 24.1 μm, P = 0.030), fibrosis score of glomerular (- 8.8%, P = 0.002), and kidney function (Cystatin C: - 701.4 pg/mL, P = 0.043; urine creatinine: - 701.4 mmol/L, P = 0.032) were significantly alleviated in DKD mice after ANT treatment compared to untreated in the 20th week. Further, proteins and metabolites in the kidneys of DKD mice were observed to be dramatically altered due to changes in amino acid metabolism with ANT treatment; mainly, taurine and hypotaurine metabolism pathway was upregulated (P = 0.0001, t value = 5.97). Furthermore, upregulated tryptophan metabolism (P < 0.0001, t value = 5.94) and tyrosine metabolism (P = 0.0037, t value = 2.91) pathways had effects on serum of DKD mice as responsed ANT regulating.CONCLUSIONS: Our results suggested that prevention of the progression of DKD by ANT could be related to the regulation of amino acid metabolism. The use of dietary ANT may be one of the dietary strategies to prevent and treat DKD.PMID:36335368 | DOI:10.1186/s12967-022-03717-9