Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Gut metabolomics and 16S rRNA sequencing analysis of the effects of arecoline on non-alcoholic fatty liver disease in rats

Thu, 13/04/2023 - 12:00
Front Pharmacol. 2023 Mar 27;14:1132026. doi: 10.3389/fphar.2023.1132026. eCollection 2023.ABSTRACTIntroduction: Non-alcoholic fatty liver disease (NAFLD) has gradually become the primary cause of fatty liver disease. Betel nuts have been used to treat gastrointestinal diseases. Methods: In the present study, we analyzed the pathology, serology, gut flora, and metabolites in a rat model of NAFLD, with and without betel nut alkaloid treatment, using an integrated approach involving pathology, serological testing, 16S rRNA gene sequencing, and ultra-performance liquid chromatography-mass spectrometry metabolomics. Results: Two rats were used for model validation. Thirty SD rats were included and divided into the normal group (C group), NAFLD model group (M group), low-dose group, medium-dose group (T group), and high-dose group with intraperitoneal injection of arecoline. The expression of blood lipids was significantly downregulated at all three arecoline concentrations (p < 0.05). Alpha-diversity analysis of the intestinal flora showed significant differences among the three groups, with a significant reduction in population diversity in the M group and a recovery of population diversity after arecoline treatment. At the phylum level, the relative abundance of Firmicutes was significantly higher in the T group and Proteobacteria in the M group. The KEGG metabolic pathways included polyketide sugar unit biosynthesis and hypertrophic cardiomyopathy. Thirty-three significantly different metabolites were identified among the groups. Significantly different metabolites between groups T and M included indolepyruvate, 2-deoxystreptamine, sakuranetin, glycyl-leucine, and riboflavin. The KEGG metabolic pathway suggested a potential role for arachidonic acid metabolism, serotonergic synapses, neuroactive ligand-receptor interactions, tyrosine metabolism, and regiomelanin. Vitamin digestion and absorption, as well as regulation of lipolysis in adipocytes, were the main metabolic pathways that distinguished the T vs. M groups. PGE2 is involved in several metabolic pathways. Correlation analysis showed that 29 bacterial species were significantly associated with PGE2 levels in the M and T groups. Vagococcus, Lawsonia, Christensenella, unidentified Erysipelotrichaceae, unidentified Coriobacteriaceae, and five other bacterial groups are unique in the PGE2 metabolic pathway regulated by arecoline. Discussion: Arecoline has lipid-lowering effects and may exert therapeutic effects in NAFLD through intestinal metabolites and intestinal flora, as well as through the Butyricicoccus/Christensenella/Coriobacteriaceae-COX2/PGE2 pathway. Thus, arecoline may represent a potential drug or target for NAFLD treatment.PMID:37050898 | PMC:PMC10083296 | DOI:10.3389/fphar.2023.1132026

Identification of the NAC Transcription Factor Family during Early Seed Development in <em>Akebia trifoliata</em> (<em>Thunb</em>.) Koidz

Thu, 13/04/2023 - 12:00
Plants (Basel). 2023 Mar 31;12(7):1518. doi: 10.3390/plants12071518.ABSTRACTThis study aimed to gain an understanding of the possible function of NACs by examining their physicochemical properties, structure, chromosomal location, and expression. Being a family of plant-specific transcription factors, NAC (petunia no apical meristem and Arabidopsis thaliana ATAF1, ATAF2, and CUC2) is involved in plant growth and development. None of the NAC genes has been reported in Akebia trifoliata (Thunb.) Koidz (A. trifoliata). In this study, we identified 101 NAC proteins (AktNACs) in the A. trifoliata genome by bioinformatic analysis. One hundred one AktNACs were classified into the following twelve categories based on the phylogenetic analysis of NAC protein: NAC-a, NAC-b, NAC-c, NAC-d, NAC-e, NAC-f, NAC-g, NAC-h, NAC-i, NAC-j, NAC-k, and NAC-l. The accuracy of the clustering results was demonstrated based on the gene structure and conserved motif analysis of AktNACs. In addition, we identified 44 pairs of duplication genes, confirming the importance of purifying selection in the evolution of AktNACs. The morphology and microstructure of early A. trifoliata seed development showed that it mainly underwent rapid cell division, seed enlargement, embryo formation and endosperm development. We constructed AktNACs co-expression network and metabolite correlation network based on transcriptomic and metabolomic data of A. trifoliata seeds. The results of the co-expression network showed that 25 AtNAC genes were co-expressed with 233 transcription factors. Metabolite correlation analysis showed that 23 AktNACs were highly correlated with 28 upregulated metabolites. Additionally, 25 AktNACs and 235 transcription factors formed co-expression networks with 141 metabolites, based on correlation analysis involving AktNACs, transcription factors, and metabolites. Notably, AktNAC095 participates in the synthesis of 35 distinct metabolites. Eight of these metabolites, strongly correlated with AktNAC095, were upregulated during early seed development. These studies may provide insight into the evolution, possible function, and expression of AktNACs genes.PMID:37050144 | DOI:10.3390/plants12071518

Metabolomics Analysis Reveals Metabolites and Metabolic Pathways Involved in the Growth and Quality of Water Dropwort [<em>Oenanthe javanica</em> (Blume) DC.] under Nutrient Solution Culture

Thu, 13/04/2023 - 12:00
Plants (Basel). 2023 Mar 27;12(7):1459. doi: 10.3390/plants12071459.ABSTRACTWater dropwort (Oenanthe javanica (Blume) DC.) is an important vegetable crop. Nutrient liquid culture has become an important cultivation method in the production of water dropwort. However, the effects of different nutrient solution cultivation methods on the growth and quality of water dropwort remains unclear. In this study, to screen the most suitable nutrient solution formula for the cultivation of water dropwort, the effects of different nutrient solution formulas (Hoagland, Cooper, Dutch greenhouse, Garden-style, Yamasaki and SCAU) on plant physiological and quality characteristics are investigated. The plant height, root length, water content (%), distribution rate of dry matter (%), chlorophyll, VC, flavonoid, total phenolic, DPPH and dietary fiber of water dropwort under different nutrient solutions were determined. According to the analytic hierarchy process (AHP) of the growth index and quality index of water dropwort under different nutrient solutions, the Yamazaki nutrient solution was considered to be the most suitable nutrient solution formula for water dropwort. To further confirm the differences of water dropwort under nutrient solution culture and soil culture, the broadly targeted metabolomics were performed. A total of 485 metabolites were detected in water dropwort under optimal nutrient solution and soil cultivation. Metabolomics analysis showed that flavonoids were the most abundant differential accumulated metabolites, and most flavonoids were up-regulated. A qRT-PCR assay indicated that the structural genes of the flavonoid biosynthesis pathway (PAL, C4H, CHS, CHI, F3H, DFR, UFGT) were significantly higher under the Yamasaki nutrient solution treatment. The current study provided a theoretical basis and technical guidance for the nutrient solution cultivation of water dropwort. Meanwhile, this study provides new insights into the study of flavonoids in water dropwort.PMID:37050085 | DOI:10.3390/plants12071459

Effects of White and Blue-Red Light on Growth and Metabolism of Basil Grown under Microcosm Conditions

Thu, 13/04/2023 - 12:00
Plants (Basel). 2023 Mar 25;12(7):1450. doi: 10.3390/plants12071450.ABSTRACTIndoor farming of basil (Ocimum basilicum L.) under artificial lighting to support year-round produce demand is an area of increasing interest. Literature data indicate that diverse light regimes differently affect downstream metabolic pathways which influence basil growth, development and metabolism. In this study, basil was grown from seedlings to fully developed plants in a microcosm, an innovative device aimed at growing plants indoor as in natural conditions. Specifically, the effects of white (W) and blue-red (BR) light under a photosynthetic photon flux density of 255 μmol m-2 s-1 on plant growth, photochemistry, soluble nutrient concentration and secondary metabolism were investigated. Plants grew taller (41.8 ± 5.0 vs. 28.4 ± 2.5 cm) and produced greater biomass (150.3 ± 24.2/14.7 ± 2.0 g vs. 116.2 ± 28.3/12.3 ± 2.5 g fresh/dry biomass) under W light compared to BR light. The two lighting conditions differently influenced the soluble nutrient concentration and the translocation rate. No photosynthetic stress was observed under the two lighting regimes, but leaves grown under W light displayed higher levels of maximum quantum yield of PSII and electron transport rate. Sharp differences in metabolic patterns under the two lighting regimes were detected with higher concentrations of phenolic compounds under the BR light.PMID:37050076 | DOI:10.3390/plants12071450

Metabolomic Study of Flavonoids in <em>Camellia drupifera</em> under Aluminum Stress by UPLC-MS/MS

Thu, 13/04/2023 - 12:00
Plants (Basel). 2023 Mar 24;12(7):1432. doi: 10.3390/plants12071432.ABSTRACTAluminum (Al) affects the yield of forest trees in acidic soils. The oil tea plant (Camellia drupifera Lour.) has high Al tolerance, with abundant phenolic compounds in its leaves, especially flavonoid compounds. The role of these flavonoids in the Al resistance of oil tea plants is unclear. In this metabolomic study of C. drupifera under Al stress, ultra-pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was utilized to identify metabolites, while principal component analysis, cluster analysis, and orthogonal partial least squares discriminant analysis were applied to analyze the data on the flavonoid metabolites. The leaf morphology of C. drupifera revealed significant damage by excess aluminum ions under each treatment compared with the control group. Under Al stress at 2 mmol/L (GZ2) and 4 mmol/L (GZ4), the total flavonoid content in C. drupifera leaves reached 24.37 and 35.64 mg/g, respectively, which are significantly higher than the levels measured in the control group (CK) (p < 0.01). In addition, we identified 25 upregulated and 5 downregulated metabolites in the GZ2 vs. CK comparison and 31 upregulated and 7 downregulated flavonoid metabolites in GZ4 vs. CK. The results demonstrate that different levels of Al stress had a significant influence on the metabolite profile of C. drupifera. It was found that the abundance of the 24 differential flavonoid metabolites was gradually elevated with increasing concentrations of Al stress, including catechin, epicatechin, naringenin-7-glucoside, astilbin, taxifolin, miquelianin, quercitrin, and quercimeritrin. Moreover, the most significant increase in antioxidant activity (about 30%) was observed in C. drupifera precultured in leaf extracts containing 7.5 and 15 μg/mL of active flavonoids. The qRT-PCR results showed that the expression levels of key genes involved in the synthesis of flavonoids were consistent with the accumulation trends of flavonoids under different concentrations of Al. Therefore, our results demonstrate the key role of flavonoid compounds in the oil tea plant C. drupifera in response to Al stress, which suggests that flavonoid metabolites in C. drupifera, as well as other aluminum-tolerant plants, may help with detoxifying aluminum.PMID:37050058 | DOI:10.3390/plants12071432

Evaluation of the Antioxidant Activities and Phenolic Profile of Shennongjia <em>Apis cerana</em> Honey through a Comparison with <em>Apis mellifera</em> Honey in China

Thu, 13/04/2023 - 12:00
Molecules. 2023 Apr 6;28(7):3270. doi: 10.3390/molecules28073270.ABSTRACTThis study evaluates the phenolic profile as well as the antioxidant properties of Shennongjia Apis cerana honey through a comparison with Apis mellifera honey in China. The total phenolic content (TPC) ranges from 263 ± 2 to 681 ± 36 mg gallic acid/kg. The total flavonoids content (TFC) ranges from 35.9 ± 0.4 to 102.2 ± 0.8 mg epicatechin/kg. The correlations between TPC or TFC and the antioxidant results (FRAP, DPPH, and ABTS) were found to be statistically significant (p < 0.01). Furthermore, the phenolic compounds are quantified and qualified by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS), and a total of 83 phenolic compounds were tentatively identified in this study. A metabolomics analysis based on the 83 polyphenols was carried out and subjected to principal component analysis and orthogonal partial least squares-discriminant analysis. The results showed that it was possible to distinguish Apis cerana honey from Apis mellifera honey based on the phenolic profile.PMID:37050033 | DOI:10.3390/molecules28073270

Metabolite Analysis of <em>Alternaria</em> Mycotoxins by LC-MS/MS and Multiple Tools

Thu, 13/04/2023 - 12:00
Molecules. 2023 Apr 6;28(7):3258. doi: 10.3390/molecules28073258.ABSTRACTAlternaria fungi are widely distributed plant pathogens that invade crop products, causing significant economic damage. In addition, toxic secondary metabolites produced by the fungi can also endanger consumers. Many of these secondary metabolites are chemically characterized as mycotoxins. In this study, Q Exactive Orbitrap mass spectrometry was used for the non-targeted analysis of the metabolome of seven Alternaria isolates cultured on Potato Carrot Agar (PCA), Potato Dextrose Agar (PDA) and Potato Sucrose Agar (PSA) medium. Due to the difficulty of detecting modified toxins, an analytical strategy with multiple visual analysis tools was also used to determine the presence of sulfate conjugated toxins, as well as to visualize the molecular network of Alternaria toxins. The results show that PSA medium exhibits more advantageous properties for the culture of Alternaria, with more toxigenic species and quantities and more obvious metabolic pathways. Based on high-resolution tandem mass spectrometry (MS/MS) data, the mycotoxins and their metabolites were mainly clustered into four groups: alternariol (AOH)/alternariol monomethyl ether (AME)/altenusin (ALU)/altenuene (ALT)/dehydroaltenusin (DHA)/Desmethyldehydroaltenusin (DMDA) families, Altertoxin-I (ATX-I) family, tentoxin (TEN) family and tenuazonic acid (TeA) family. Moreover, the PSA medium is more suitable for the accumulation of AOH, AME, ALU, ALT, DHA and DMDA, while the PDA medium is more suitable for the accumulation of ATX-I, TEN and TeA. This research may provide theoretical support for the metabolomics study of Alternaria.PMID:37050021 | DOI:10.3390/molecules28073258

Scutellarin Alleviates Ischemic Brain Injury in the Acute Phase by Affecting the Activity of Neurotransmitters in Neurons

Thu, 13/04/2023 - 12:00
Molecules. 2023 Apr 4;28(7):3181. doi: 10.3390/molecules28073181.ABSTRACTCerebral ischemic stroke is a common neuron loss disease that is caused by the interruption of the blood supply to the brain. In order to enhance the CIS outcome, both identifying the treatment target of ischemic brain damage in the acute phase and developing effective therapies are urgently needed. Scutellarin had been found to be beneficial to ischemic injuries and has been shown to have potent effects in clinical application on both stroke and myocardial infarction. However, whether scutellarin improves ischemic brain damage in the acute phase remains unknown. In this study, the protective effects of scutellarin on ischemic brain damage in the acute phase (within 12 h) were illustrated. In middle cerebral artery occlusion and reperfusion (MCAO/R) modeling rats, the Z-Longa score was significantly down-regulated by 25% and 23.1%, and the brain infarct size was reduced by 26.95 ± 0.03% and 25.63 ± 0.02% when responding to high-dose and low-dose scutellarin treatments, respectively. H&E and TUNEL staining results indicated that the neuron loss of the ischemic region was improved under scutellarin treatment. In order to investigate the mechanism of scutellarin's effects on ischemic brain damage in the acute phase, changes in proteins and metabolites were analyzed. The suppression of scutellarin on the glutamate-inducing excitatory amino acid toxicity was strongly indicated in the study of both proteomics and metabolomics. A molecular docking experiment presented strong interactions between scutellarin and glutamate receptors, which score much higher than those of memantine. Further, by performing a parallel reaction monitoring-mass spectrometry (PRM-MS) study on both the cortex and hippocampus tissue of the ischemic region, we screened the scutellarin-regulating molecules that are involved in both the release and transportation of neurotransmitters. It was found that the aberrant levels of glutamate receptors, including EAAT2, GRIN1, GRIN2B, and GRM1, as well as of other glutamatergic pathway-involving proteins, including CAMKK2, PSD95, and nNOS, were significantly regulated in the ischemic cortex. In the hippocampus, EAAT2, GRIN1, nNOS, and CAM were significantly regulated. Taken together, scutellarin exerts potent effects on ischemic brain damage in the acute phase by regulating the activity of neurotransmitters and reducing the toxicity of excitatory amino acids in in neurons.PMID:37049959 | DOI:10.3390/molecules28073181

Activation-Free Sulfonyl Fluoride Probes for Fragment Screening

Thu, 13/04/2023 - 12:00
Molecules. 2023 Mar 29;28(7):3042. doi: 10.3390/molecules28073042.ABSTRACTSuFEx chemistry is based on the unique reactivity of the sulfonyl fluoride group with a range of nucleophiles. Accordingly, sulfonyl fluorides label multiple nucleophilic amino acid residues, making these reagents popular in both chemical biology and medicinal chemistry applications. The reactivity of sulfonyl fluorides nominates this warhead chemotype as a candidate for an external, activation-free general labelling tag. Here, we report the synthesis and characterization of a small sulfonyl fluoride library that yielded the 3-carboxybenzenesulfonyl fluoride warhead for tagging tractable targets at nucleophilic residues. Based on these results, we propose that coupling diverse fragments to this warhead would result in a library of sulfonyl fluoride bits (SuFBits), available for screening against protein targets. SuFBits will label the target if it binds to the core fragment, which facilitates the identification of weak fragments by mass spectrometry.PMID:37049805 | DOI:10.3390/molecules28073042

Nontargeted Screening for Flavonoids in Salicornia Plant by Reversed-Phase Liquid Chromatography-Electrospray Orbitrap Data-Dependent MS<sup>2</sup>/MS<sup>3</sup>

Thu, 13/04/2023 - 12:00
Molecules. 2023 Mar 28;28(7):3022. doi: 10.3390/molecules28073022.ABSTRACTThe Salicornia genus has great potential in agrifood industries because of its nutritional benefits related to its high content of antioxidant compounds, including flavonoids. A nontargeted method based on reversed-phase liquid chromatography-electrospray orbitrap data-dependent MS2/MS3 and the fragment ion search (FISh) strategy was developed to screen flavonoids in Salicornia plants. An extensive study of fragmentation of a set of flavonoid standards allowed for the definition of 15 characteristic fragment ions for flagging flavonoids in the plant matrix. The nontargeted analysis was applied to Salicornia europaea species and allowed for the annotation of 25 candidate flavonoids, including 14 that had not been reported previously. Structural prediction of two unreported flavonoids and their isomeric forms was based on an advanced data processing method using an in silico approach and in-house databases compiling flavonoid-specific chemical substitution. Finally, the method developed allowed for the optimization of extraction yields of flavonoids from the plant matrix.PMID:37049782 | DOI:10.3390/molecules28073022

Metabolomic Analysis of Phytochemical Compounds from Ethanolic Extract of Lime (<em>Citrus aurantifolia</em>) Peel and Its Anti-Cancer Effects against Human Hepatocellular Carcinoma Cells

Thu, 13/04/2023 - 12:00
Molecules. 2023 Mar 26;28(7):2965. doi: 10.3390/molecules28072965.ABSTRACTLime peels are food waste from lime product manufacturing. We previously developed and optimized a green extraction method for hesperidin-limonin-rich lime peel extract. This study aimed to identify the metabolomics profile of phytochemicals and the anti-cancer effects of ethanolic extract of lime (Citrus aurantifolia) peel against liver cancer cells PLC/PRF/5. The extract's metabolomics profile was analyzed by using LC-qTOF/MS and GC-HRMS. The anti-cancer effects were studied by using MTT assay, Annexin-PI assay, and Transwell-invasion assay. Results show that the average IC50(s) of hesperidin, limonin, and the extract on cancer cells' viability were 165.615, 188.073, and 503.004 µg/mL, respectively. At the IC50 levels, the extract induced more apoptosis than those of pure compounds when incubating for 24 and 48 h (p < 0.0001). A combination of limonin and hesperidin showed a synergistic effect on apoptosis induction (p < 0.001), but the effect of the combination was still less than that of the extract at 48 h. Furthermore, the extract significantly inhibited cancer cell invasion better than limonin but equal to hesperidin. At the IC50 level, the extract contains many folds lower amounts of hesperidin and limonin than the IC50 doses of the pure compounds. Besides limonin and hesperidin, there were another 60 and 22 compounds detected from the LCMS and GCMS analyses, respectively. Taken altogether, the superior effect of the ethanolic extract against liver cancer cells compared to pure compound likely results from the combinatorial effects of limonin, hesperidin, and other phytochemical components in the extract.PMID:37049726 | DOI:10.3390/molecules28072965

Discrepancy Study of the Chemical Constituents of Panax Ginseng from Different Growth Environments with UPLC-MS-Based Metabolomics Strategy

Thu, 13/04/2023 - 12:00
Molecules. 2023 Mar 24;28(7):2928. doi: 10.3390/molecules28072928.ABSTRACTPanax ginseng (P. ginseng), the dried root and rhizome of P. ginseng C. A. Meyer, is widely used in many fields as dietary supplements and medicine. To characterize the chemical constituents in P. ginseng cultivated in different growth environments, a UPLC-TOF-MS method was established for qualitative analysis. Four hundred and eight ginsenosides, including 81 new compounds, were characterized in P. ginseng from different regions. Among the detected compounds, 361 ginsenosides were recognized in P. ginseng cultivated in the region of Monsoon Climate of Medium Latitudes, possessing the largest amount of ginsenosides in all samples. Furthermore, 41 ginsenosides in 12 batches of P. ginsengs were quantified with a UPLC-MRM-MS method, and P. ginsengs from different regions were distinguished via chemometric analysis. This study showed that the different environments have a greater influence on P. ginseng, which laid a foundation for further quality control of the herb.PMID:37049688 | DOI:10.3390/molecules28072928

Characteristics of the Gut Microbiome and Serum Metabolome in Patients with Functional Constipation

Thu, 13/04/2023 - 12:00
Nutrients. 2023 Apr 6;15(7):1779. doi: 10.3390/nu15071779.ABSTRACTFunctional constipation (FC) is a gastrointestinal disorder with high incidence, and it seriously affects patients' physical and mental health. Several studies have shown that the gut microbiome is associated with FC, but these studies have produced inconsistent findings, with few reflecting the relationship between the gut microbiome and metabolites. This study used 16S rRNA microbial genomics and non-target metabolome based on liquid chromatography-mass spectrometry to analyze the gut microbiota composition and serum metabolic profiles of 30 FC patients and 28 healthy individuals. We found that patients with FC and healthy individuals have different gut microbiota structures and serum metabolic profiles. FC patients had more Bacteroides and butyrate-producing bacteria (Roseburia, Faecaliberium, Butyriccoccus). The upstream products of host arginine biosynthesis (2-oxoglutaric acid, L-glutamic acid, N-acetylornithine, and L-ornithine) were significantly reduced in FC patients' serum metabolites. In summary, our study describes the gut microbiome and serum metabolome of patients with functional constipation. It reveals that functional constipation may be associated with increased Bacteroidetes and downregulation of upstream products of host arginine biosynthesis, which may be potential markers for diagnosing functional constipation.PMID:37049619 | DOI:10.3390/nu15071779

<em>Lactobacillus plantarum</em> CCFM405 against Rotenone-Induced Parkinson's Disease Mice via Regulating Gut Microbiota and Branched-Chain Amino Acids Biosynthesis

Thu, 13/04/2023 - 12:00
Nutrients. 2023 Apr 1;15(7):1737. doi: 10.3390/nu15071737.ABSTRACTRecent studies have demonstrated that disturbances in the gut microbiota and microbiota -derived metabolites contribute to the pathogenesis of Parkinson's disease (PD), suggesting that probiotic treatments that restore them may delay disease progression. This study aimed to examine the attenuating efficacy of L. plantarum CCFM405 and the potential mechanisms in mice with rotenone-induced PD. Our results indicate that L. plantarum CCFM405 ameliorated rotenone-induced motor deficits and constipation, decreased dopaminergic neuronal death, reduced intestinal inflammation and neuroinflammation, and raised dopamine levels, 5-HT, and associated metabolites in the striatal region of the brain in mice with PD. Sequencing of 16S rRNA from fecal microbiota revealed that L. plantarum CCFM405 normalized the gut bacterial composition in mice with PD, as evidenced by the increased relative abundance of the following genus, Bifidobacterium, Turicibacter, and Faecalibaculum, and decreased relative abundance of Alistipes, Bilophila, Akkermansia, and Escherichia-Shigella. The PICRUSt-predicted gut microbiota function revealed that L. plantarum CCFM405 enhanced the biosynthesis of amino acid pathways, particularly valine, leucine, and isoleucine (branched-chain amino acids, BCAAs). A non-metabolomic analysis of the serum and feces showed that L. plantarum CCFM405 markedly increased the levels of BCAAs. Pathway enrichment analysis based on the KEGG database further suggested that L. plantarum CCFM405 supplementation can promote BCAAs biosynthesis. Collectively, L. plantarum CCFM405 can help to prevent rotenone-induced PD by modulating the gut microbiota-metabolite axis. BCAAs may play a dominant role in L. plantarum CCFM405-associated neuroprotection in PD mice. This probiotic could be utilized as a potential food supplement in the management of PD.PMID:37049578 | DOI:10.3390/nu15071737

Metabolomics Analysis Reveals Molecular Signatures of Metabolic Complexity in Children with Hypercholesterolemia

Thu, 13/04/2023 - 12:00
Nutrients. 2023 Mar 31;15(7):1726. doi: 10.3390/nu15071726.ABSTRACTDespite the importance of hypercholesterolemia in children, it is overlooked, and there are currently few metabolomics-based approaches available to understand its molecular mechanisms. Children from a birth cohort had their cholesterol levels measured with the aim of identifying the metabolites for the molecular biological pathways of childhood hypercholesterolemia. One hundred and twenty-five children were enrolled and stratified into three groups according to cholesterol levels (acceptable, <170 mg/dL, n = 42; borderline, 170-200 mg/dL, n = 52; and high, >200 mg/dL, n = 31). Plasma metabolomic profiles were obtained by using 1H-nuclear magnetic resonance (NMR) spectroscopy, and partial least squares-discriminant analysis (PLS-DA) was applied using the MetaboAnalyst 5.0 platform. Metabolites significantly associated with different cholesterol statuses were identified, and random forest classifier models were used to rank the importance of these metabolites. Their associations with serum lipid profile and functional metabolic pathways related to hypercholesterolemia were also assessed. Cholesterol level was significantly positively correlated with LDL-C and Apo-B level, as well as HDL-C and Apo-A1 level separately, whereas HDL-C was negatively correlated with triglyceride level (p < 0.01). Eight metabolites including tyrosine, glutamic acid, ornithine, lysine, alanine, creatinine, oxoglutaric acid, and creatine were significantly associated with the different statuses of cholesterol level. Among them, glutamic acid and tyrosine had the highest importance for different cholesterol statuses using random forest regression models. Carbohydrate and amino acid metabolisms were significantly associated with different cholesterol statuses, with glutamic acid being involved in all amino acid metabolic pathways (FDR-adjusted p < 0.01). Hypercholesterolemia is a significant health concern among children, with up to 25% having high cholesterol levels. Glutamic acid and tyrosine are crucial amino acids in lipid metabolism, with glutamic-acid-related amino acid metabolism playing a significant role in regulating cholesterol levels.PMID:37049565 | DOI:10.3390/nu15071726

Integration of Metabolomics and Transcriptomics to Reveal the Metabolic Characteristics of Exercise-Improved Bone Mass

Thu, 13/04/2023 - 12:00
Nutrients. 2023 Mar 30;15(7):1694. doi: 10.3390/nu15071694.ABSTRACT(1) Background: Exercise is effective in promoting and maintaining bone mass. The aim of this study was to detect the exercise-induced metabolic changes in bone tissue of zebrafish. (2) Methods: Thirty-eight zebrafish (Danio rerio, six months old) were analyzed. The exercise group (n = 19) received 8 weeks of counter-current swimming training. The control group (n = 19) was not subjected to exercise. Mineralization was quantified, and alkaline phosphatase (Alp) and anti-tartrate acid phosphatase (Trap) activities were estimated (n = 12). The metabolomics (n = 12) and transcriptomics (n = 14) data of bone tissue were used for the integration analyses. (3) Results: The results showed that the exercise training improved the bone mineralization of zebrafish, e.g., the exercise group (5.74 × 104 ± 7.63 × 103) had a higher mean optical density than the control group (5.26 × 104 ± 8.56 × 103, p = 0.046) for the caudal vertebrae. The amount of mineralized matrix in scales of the exercised zebrafish was also higher (0.156 ± 0.012 vs. 0.102 ± 0.003, p = 0.005). Both histological staining and biochemical analysis revealed increased Alp activity (0.81 ± 0.26 vs. 0.76 ± 0.01, p = 0.002) and decreased Trap activity (1.34 ± 0.01 vs. 1.36 ± 0.01, p = 0.005) in the exercise group. A total of 103 different metabolites (DMs, VIP ≥ 1, fold change (FC) ≥ 1.20 or ≤0.83, p < 0.050) were identified. Alanine, aspartate and glutamate metabolism, β-alanine metabolism, pyrimidine metabolism, and pantothenate and CoA biosynthesis were the significantly enriched metabolic pathways (p < 0.050). A total of 35 genes (q ≤ 0.050 (BH), |Log2FC| ≥ 0.5) were coenriched with the 103 DMs in the four identified pathways. Protein-protein interaction network analysis of the 35 genes showed that entpd3, entpd1, and cmpk2 were the core genes. (4) Conclusions: The results of this study suggest that alanine, aspartate and glutamate metabolism, β-alanine metabolism, pyrimidine metabolism, and pantothenate and CoA biosynthesis contributed to exercise-induced improvements in bone mass.PMID:37049535 | DOI:10.3390/nu15071694

Intestinal Barrier Dysfunction and Microbiota-Gut-Brain Axis: Possible Implications in the Pathogenesis and Treatment of Autism Spectrum Disorder

Thu, 13/04/2023 - 12:00
Nutrients. 2023 Mar 27;15(7):1620. doi: 10.3390/nu15071620.ABSTRACTAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder with multifactorial etiology, characterized by impairment in two main functional areas: (1) communication and social interactions, and (2) skills, interests and activities. ASD patients often suffer from gastrointestinal symptoms associated with dysbiotic states and a "leaky gut." A key role in the pathogenesis of ASD has been attributed to the gut microbiota, as it influences central nervous system development and neuropsychological and gastrointestinal homeostasis through the microbiota-gut-brain axis. A state of dysbiosis with a reduction in the Bacteroidetes/Firmicutes ratio and Bacteroidetes level and other imbalances is common in ASD. In recent decades, many authors have tried to study and identify the microbial signature of ASD through in vivo and ex vivo studies. In this regard, the advent of metabolomics has also been of great help. Based on these data, several therapeutic strategies, primarily the use of probiotics, are investigated to improve the symptoms of ASD through the modulation of the microbiota. However, although the results are promising, the heterogeneity of the studies precludes concrete evidence. The aim of this review is to explore the role of intestinal barrier dysfunction, the gut-brain axis and microbiota alterations in ASD and the possible role of probiotic supplementation in these patients.PMID:37049461 | DOI:10.3390/nu15071620

Circulating Metabolomic and Lipidomic Signatures Identify a Type 2 Diabetes Risk Profile in Low-Birth-Weight Men with Non-Alcoholic Fatty Liver Disease

Thu, 13/04/2023 - 12:00
Nutrients. 2023 Mar 24;15(7):1590. doi: 10.3390/nu15071590.ABSTRACTThe extent to which increased liver fat content influences differences in circulating metabolites and/or lipids between low-birth-weight (LBW) individuals, at increased risk of type 2 diabetes (T2D), and normal-birth-weight (NBW) controls is unknown. The objective of the study was to perform untargeted serum metabolomics and lipidomics analyses in 26 healthy, non-obese early-middle-aged LBW men, including five men with screen-detected and previously unrecognized non-alcoholic fatty liver disease (NAFLD), compared with 22 age- and BMI-matched NBW men (controls). While four metabolites (out of 65) and fifteen lipids (out of 279) differentiated the 26 LBW men from the 22 NBW controls (p ≤ 0.05), subgroup analyses of the LBW men with and without NAFLD revealed more pronounced differences, with 11 metabolites and 56 lipids differentiating (p ≤ 0.05) the groups. The differences in the LBW men with NAFLD included increased levels of ornithine and tyrosine (PFDR ≤ 0.1), as well as of triglycerides and phosphatidylcholines with shorter carbon-chain lengths and fewer double bonds. Pathway and network analyses demonstrated downregulation of transfer RNA (tRNA) charging, altered urea cycling, insulin resistance, and an increased risk of T2D in the LBW men with NAFLD. Our findings highlight the importance of increased liver fat in the pathogenesis of T2D in LBW individuals.PMID:37049431 | DOI:10.3390/nu15071590

All-Tunicate Cellulose Film with Good Light Management Properties for High-Efficiency Organic Solar Cells

Thu, 13/04/2023 - 12:00
Nanomaterials (Basel). 2023 Mar 29;13(7):1221. doi: 10.3390/nano13071221.ABSTRACTTunicate nanocellulose with its unique properties, such as excellent mechanical strength, high crystallinity, and good biodegradability, has potential to be used for the preparation of light management film with tunable transmittance and haze. Herein, we prepared a whole tunicate cellulose film with tunable haze levels, by mixing tunicate microfibrillated cellulose (MFC) and tunicate cellulose nanofibrils (CNF). Then, the obtained whole tunicate cellulose film with updated light management was used to modify the organic solar cell (OSC) substrate, aiming to improve the light utilization efficiency of OSC. Results showed that the dosage of MFC based on the weight of CNF was an important factor to adjust the haze and light transmittance of the prepared cellulose film. When the dosage of MFC was 3 wt.%, the haze of the obtained film increased 74.2% compared to the pure CNF film (39.2%). Moreover, the optimized tunicate cellulose film exhibited excellent mechanical properties (e.g., tensile strength of 168 MPa, toughness of 5.7 MJ/m3) and high thermal stability, which will be beneficial to the workability and durability of OSC. More interestingly, we applied the obtained whole tunicate cellulose film with a high haze (68.3%) and high light transmittance (85.0%) as an additional layer to be adhered to the glass substrate of OSC, and a notable improvement (6.5%) of the power conversion efficiency was achieved. With the use of biodegradable tunicate cellulose, this work provides a simple strategy to enhance light management of the transparent substrate of OSC for improving power conversion efficiency.PMID:37049313 | DOI:10.3390/nano13071221

Effects of Natural and Synthetic Astaxanthin on Growth, Body Color, and Transcriptome and Metabolome Profiles in the Leopard Coralgrouper (<em>Plectropomus leopardus</em>)

Thu, 13/04/2023 - 12:00
Animals (Basel). 2023 Apr 4;13(7):1252. doi: 10.3390/ani13071252.ABSTRACTNatural and synthetic astaxanthin can promote pigmentation in fish. In this study, the effects of dietary astaxanthin on growth and pigmentation were evaluated in leopard coralgrouper (Plectropomus leopardus). Fish were assigned to three groups: 0% astaxanthin (C), 0.02% natural astaxanthin (HP), and 0.02% synthetic astaxanthin (AS). Brightness (L*) was not influenced by astaxanthin. However, redness (a*) and yellowness (b*) were significantly higher for fish fed astaxanthin-containing diets than fish fed control diets and were significantly higher in the HP group than in the AS group. In a transcriptome analysis, 466, 33, and 32 differentially expressed genes (DEGs) were identified between C and HP, C and AS, and AS and HP, including various pigmentation-related genes. DEGs were enriched for carotenoid deposition and other pathways related to skin color. A metabolome analysis revealed 377, 249, and 179 differential metabolites (DMs) between C and HP, C and AS, and AS and HP, respectively. In conclusion, natural astaxanthin has a better coloration effect on P. leopardus, which is more suitable as a red colorant in aquaculture. These results improve our understanding of the effects of natural and synthetic astaxanthin on red color formation in fish.PMID:37048508 | DOI:10.3390/ani13071252

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