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1.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2856-2869, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472303

RESUMO

The environmental gas concentration affects the storage period and quality of fruits and vegetables. High concentration CO2 treating for a long time will cause damage to fruits, However, the specific molecular mechanism is unclear. To analyze the mechanism of CO2 injury in apple, high-throughput sequencing technology of Illumina Hiseq 4000 and non-targeted metabolism technology were used to analyze the transcriptome sequencing and metabolomics analysis of browning flesh tissue of damage fruit and normal pulp tissue of the control group. A total of 6 332 differentially expressed genes were obtained, including 4 187 up-regulated genes and 2 145 down regulated genes. Functional analysis of the differentially expressed genes confirmed that the occurrence of CO2 injury in apple was related to redox process, lipid metabolism, hormone signal transduction process and energy metabolism process. Twenty candidate browning genes were successfully screened, among which grxcr1 (md14g1137800) and gpx (md06g1081300) participated in the reactive oxygen species scavenging process, and pld1_ 2 (md15g1125000) and plcd (md07g1221900) participated in phospholipid acid synthesis and affected membrane metabolism. mdh1 (md05g1238800) participated in TCA cycle and affected energy metabolism. A total of 77 differential metabolites were obtained by metabolomic analysis, mainly organic acids, lipids, sugars and polyketones, including 35 metabolites related to browning. The metabolism of flavonoids was involved in the browning process of apple. Compared with the control tissue, the content of flavonoids such as catechin and quercetin decreased significantly in the damaged apple tissue, the antioxidant capacity of cells decreased, the redox state was unbalanced, and the cell structure was destroyed, resulting in browning. The results of this study further enrich the theoretical basis of CO2 damage, and provide reference for the practical application of high concentration CO2 preservation technology.


Assuntos
Malus , Dióxido de Carbono , Frutas , Regulação da Expressão Gênica de Plantas , Malus/genética , Metaboloma , Transcriptoma
2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 536-544, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494523

RESUMO

Objective To obtain the metabolome profiles in liver and serum of mice during normal aging. Methods The liver and serum samples of ten 2-month-old mice and ten 18-month-old C57BL/6J mice under physiological conditions were collected.Metabolites were identified and quantified by liquid chromatography-tandem mass spectrometry.The overall assessment,differential screening,and functional analysis were performed with the filtered high-quality data. Results In the negative-ion mode and positive-ion mode,242 and 399 metabolites were identified in the liver and 265 and 230 in serum,respectively.The difference of metabolome between young and old mice was moderate.The upregulated metabolites identified in aging liver were related to the metabolism of riboflavin,glucose,and arachidonic acid,while the downregulated ones were associated with the metabolism of pyrimidine,purine,glycerophospholipid,glutathione,and nicotinamide.Altered metabolites in serum during aging were involved in a variety of nucleic acid metabolism-related pathways,such as pyrimidine metabolism,purine metabolism,one carbon pool by folate,and amino sugar and nucleotide sugar metabolism. Conclusions The metabolome profiles of mouse liver and serum both revealed dysregulated nucleic acid metabolism pathways during normal aging.This study provides metabolome data for further research on aging-associated mechanism and may support the discovery of intervention methods for aging.


Assuntos
Metaboloma , Metabolômica , Envelhecimento , Animais , Fígado , Camundongos , Camundongos Endogâmicos C57BL
3.
Front Cell Infect Microbiol ; 11: 694470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395309

RESUMO

Pathophysiology of visceral leishmaniasis (VL) is not fully understood and it has been widely accepted that the parasitic components and host immune response both contribute to the perpetuation of the disease. Host alterations during leishmaniasis is a feebly touched area that needs to be explored more to better understand the VL prognosis and diagnosis, which are vital to reduce mortality and post-infection sequelae. To address this, we performed untargeted metabolomics of Leishmania donovani (Ld) infected, uninfected and treated BALB/c mice's tissues and biofluids to elucidate the host metabolome changes using gas chromatography-mass spectrometry. Univariate and multivariate data treatments provided numerous significant differential hits in several tissues like the brain, liver, spleen and bone marrow. Differential modulations were also observed in serum, urine and fecal samples of Ld-infected mice, which could be further targeted for biomarker and diagnostic validations. Several metabolic pathways were found to be upregulated/downregulated in infected (TCA, glycolysis, fatty acids, purine and pyrimidine, etcetera) and treated (arginine, fumaric acid, orotic acid, choline succinate, etcetera) samples. Results also illustrated several metabolites with different pattern of modulations in control, infected and treated samples as well as in different tissues/biofluids; for e.g. glutamic acid identified in the serum samples of infected mice. Identified metabolites include a range of amino acids, saccharides, energy-related molecules, etcetera. Furthermore, potential biomarkers have been identified in various tissues-arginine and fumaric acid in brain, choline in liver, 9-(10) EpOME in spleen and bone marrow, N-acetyl putrescine in bone marrow, etcetera. Among biofluids, glutamic acid in serum, hydrazine and deoxyribose in urine and 3-Methyl-2-oxo pentanoic acid in feces are some of the potential biomarkers identified. These metabolites could be further looked into for their role in disease complexity or as a prognostic marker. The presented profiling approach allowed us to attain a metabolic portrait of the individual tissue/biofluid modulations during VL in the host and represent a valuable system readout for further studies. Our outcomes provide an improved understanding of perturbations of the host metabolome interface during VL, including identification of many possible potential diagnostic and therapeutic targets.


Assuntos
Leishmania donovani , Leishmaniose Visceral , Animais , Metaboloma , Metabolômica , Camundongos , Camundongos Endogâmicos BALB C
4.
Nat Commun ; 12(1): 4845, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381036

RESUMO

The human gut microbiota is increasingly recognized as an important factor in modulating innate and adaptive immunity through release of ligands and metabolites that translocate into circulation. Urbanizing African populations harbor large intestinal diversity due to a range of lifestyles, providing the necessary variation to gauge immunomodulatory factors. Here, we uncover a gradient of intestinal microbial compositions from rural through urban Tanzanian, towards European samples, manifested both in relative abundance and genomic variation observed in stool metagenomics. The rural population shows increased Bacteroidetes, led by Prevotella copri, but also presence of fungi. Measured ex vivo cytokine responses were significantly associated with 34 immunomodulatory microbes, which have a larger impact on circulating metabolites than non-significant microbes. Pathway effects on cytokines, notably TNF-α and IFN-γ, differential metabolome analysis and enzyme copy number enrichment converge on histidine and arginine metabolism as potential immunomodulatory pathways mediated by Bifidobacterium longum and Akkermansia muciniphila.


Assuntos
Citocinas/imunologia , Microbioma Gastrointestinal/fisiologia , População Rural , População Urbana , Adulto , Arginina/metabolismo , Bactérias/imunologia , Bactérias/isolamento & purificação , Bactérias/metabolismo , Dieta , Feminino , Microbioma Gastrointestinal/imunologia , Histidina/metabolismo , Humanos , Imunomodulação , Masculino , Redes e Vias Metabólicas , Metaboloma/imunologia , Fatores Socioeconômicos , Tanzânia , Urbanização
5.
Sensors (Basel) ; 21(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34450881

RESUMO

Electronic noses (e-nose) offer potential for the detection of cancer in its early stages. The ability to analyse samples in real time, at a low cost, applying easy-to-use and portable equipment, gives e-noses advantages over other technologies, such as Gas Chromatography-Mass Spectrometry (GC-MS). For diseases such as cancer with a high mortality, a technology that can provide fast results for use in routine clinical applications is important. Colorectal cancer (CRC) is among the highest occurring cancers and has high mortality rates, if diagnosed late. In our study, we investigated the use of portable electronic nose (PEN3), with further analysis using GC-TOF-MS, for the analysis of gases and volatile organic compounds (VOCs) to profile the urinary metabolome of colorectal cancer. We also compared the different cancer stages with non-cancers using the PEN3 and GC-TOF-MS. Results obtained from PEN3, and GC-TOF-MS demonstrated high accuracy for the separation of CRC and non-cancer. PEN3 separated CRC from non-cancerous group with 0.81 AUC (Area Under the Curve). We used data from GC-TOF-MS to obtain a VOC profile for CRC, which identified 23 potential biomarker VOCs for CRC. Thus, the PEN3 and GC-TOF-MS were found to successfully separate the cancer group from the non-cancer group.


Assuntos
Neoplasias Colorretais , Compostos Orgânicos Voláteis , Neoplasias Colorretais/diagnóstico , Nariz Eletrônico , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Metaboloma , Compostos Orgânicos Voláteis/análise
6.
Anal Chem ; 93(32): 11099-11107, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34347447

RESUMO

As a vital hub, a mitochondrion houses metabolic pathways that play important roles in cellular physiology. Aberrant metabolites occurring in mitochondria are closely associated with the emergence and progression of various mitochondria-related diseases. Therefore, a simple and versatile approach to efficiently purify intact mitochondria is urgently needed to precisely and comprehensively characterize the composition and abundance of the mitochondrial metabolome in different physiological and pathological states. In this work, novel immunoaffinitive magnetic composites MagG@PD@Avidin@TOM20 were prepared to achieve highly selective isolation of intact mitochondria from three different hepatocytes (LO2, HepG2, and Huh7). The prepared composites inherit combined merits, including strong magnetic responsiveness, excellent stability, and specific and high affinity between antibody TOM20 and mitochondrial outer membrane protein. These mitochondria attached on MagG@PD@Avidin@TOM20 were characterized by the western blot and fluorescence microscopy to confirm their purity and integrity, which are vital for reliable mitochondrial metabolic analysis. Subsequently, ultrahigh-performance liquid chromatography-high-resolution mass spectrometry-based untargeted metabolomics analysis was conducted to characterize the metabolomes in the immunopurified mitochondria and whole cells. Notably, the metabolite profiles of whole cells and mitochondria including itaconic acid, acetylcarnitine, malic acid, etc., were significantly different. These data underscore the importance of determining metabolites at the mitochondrial level, which would supplement us new knowledge at the subcellular level.


Assuntos
Metaboloma , Metabolômica , Grafite , Indóis , Fenômenos Magnéticos , Mitocôndrias/metabolismo , Polímeros
7.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360606

RESUMO

The combination of natural products with standard chemotherapeutic agents offers a promising strategy to enhance the efficacy or reduce the side effects of standard chemotherapy. Doxorubicin (DOX), a standard drug for breast cancer, has several disadvantages, including severe side effects and the development of drug resistance. Recently, we reported the potential bioactive markers of Australian propolis extract (AP-1) and their broad spectrum of pharmacological activities. In the present study, we explored the synergistic interactions between AP-1 and DOX in the MCF7 breast adenocarcinoma cells using different synergy quantitation models. Biochemometric and metabolomics-driven analysis was performed to identify the potential anticancer metabolites in AP-1. The molecular mechanisms of synergy were studied by analysing the apoptotic profile via flow cytometry, apoptotic proteome array and measuring the oxidative status of the MCF7 cells treated with the most synergistic combination. Furthermore, label-free quantification proteomics analysis was performed to decipher the underlying synergistic mechanisms. Five prenylated stilbenes were identified as the key metabolites in the most active AP-1 fraction. Strong synergy was observed when AP-1 was combined with DOX in the ratio of 100:0.29 (w/w) as validated by different synergy quantitation models implemented. AP-1 significantly enhanced the inhibitory effect of DOX against MCF7 cell proliferation in a dose-dependent manner with significant inhibition of the reactive oxygen species (p < 0.0001) compared to DOX alone. AP-1 enabled the reversal of DOX-mediated necrosis to programmed cell death, which may be advantageous to decline DOX-related side effects. AP-1 also significantly enhanced the apoptotic effect of DOX after 24 h of treatment with significant upregulation of catalase, HTRA2/Omi, FADD together with DR5 and DR4 TRAIL-mediated apoptosis (p < 0.05), contributing to the antiproliferative activity of AP-1. Significant upregulation of pro-apoptotic p27, PON2 and catalase with downregulated anti-apoptotic XIAP, HSP60 and HIF-1α, and increased antioxidant proteins (catalase and PON2) may be associated with the improved apoptosis and oxidative status of the synergistic combination-treated MCF7 cells compared to the mono treatments. Shotgun proteomics identified 21 significantly dysregulated proteins in the synergistic combination-treated cells versus the mono treatments. These proteins were involved in the TP53/ATM-regulated non-homologous end-joining pathway and double-strand breaks repairs, recruiting the overexpressed BRCA1 and suppressed RIF1 encoded proteins. The overexpression of UPF2 was noticed in the synergistic combination treatment, which could assist in overcoming doxorubicin resistance-associated long non-coding RNA and metastasis of the MCF7 cells. In conclusion, we identified the significant synergy and highlighted the key molecular pathways in the interaction between AP-1 and DOX in the MCF7 cells together with the AP-1 anticancer metabolites. Further in vivo and clinical studies are warranted on this synergistic combination.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Metaboloma/efeitos dos fármacos , Própole/farmacologia , Proteoma/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Quimioterapia Combinada , Feminino , Humanos , Células MCF-7
8.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445541

RESUMO

Mallotus japonicus is a valuable traditional medicinal plant in East Asia for applications as a gastrointestinal drug. However, the molecular components involved in the biosynthesis of bioactive metabolites have not yet been explored, primarily due to a lack of omics resources. In this study, we established metabolome and transcriptome resources for M. japonicus to capture the diverse metabolite constituents and active transcripts involved in its biosynthesis and regulation. A combination of untargeted metabolite profiling with data-dependent metabolite fragmentation and metabolite annotation through manual curation and feature-based molecular networking established an overall metabospace of M. japonicus represented by 2129 metabolite features. M. japonicus de novo transcriptome assembly showed 96.9% transcriptome completeness, representing 226,250 active transcripts across seven tissues. We identified specialized metabolites biosynthesis in a tissue-specific manner, with a strong correlation between transcripts expression and metabolite accumulations in M. japonicus. The correlation- and network-based integration of metabolome and transcriptome datasets identified candidate genes involved in the biosynthesis of key specialized metabolites of M. japonicus. We further used phylogenetic analysis to identify 13 C-glycosyltransferases and 11 methyltransferases coding candidate genes involved in the biosynthesis of medicinally important bergenin. This study provides comprehensive, high-quality multi-omics resources to further investigate biological properties of specialized metabolites biosynthesis in M. japonicus.


Assuntos
Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Mallotus (Planta)/metabolismo , Metaboloma , Proteínas de Plantas/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Mallotus (Planta)/genética , Mallotus (Planta)/crescimento & desenvolvimento , Especificidade de Órgãos , Filogenia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo
9.
Anal Chem ; 93(34): 11701-11709, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34461730

RESUMO

Off-line combination of countercurrent separation (CCS) and quantitative 1H NMR (qHNMR) methodologies enabled the systematic dissection and gravimetric quantification of a chemically complex Rhodiola rosea crude extract (RCE). The loss-free nature and high selectivity of CCS achieved the quantitative discrimination of fatty acids (FAs), sugars, and proanthocyanidins (PACs) from ten other metabolite classes: phenylpropanoids, phenylethanoids, acyclic monoterpenoid glycosides, pinene derived glycosides, benzyl alcohol glycosides, cyanogenic glycosides, flavonoids, gallic acids, methylparabens, and cuminol glycosides. The ability of CCS to remove ("knockout") PACs completely resolved challenges with baselines that plague NMR and UHPLC analyses and produce inaccurate integral and AUC quantitation, respectively. NMR analysis of the non-PAC fractions enabled unambiguous identification of metabolites and their characteristic resonances for subsequent multitarget absolute quantification by qHNMR using a single, nonidentical internal calibrant (IC). An orthogonal LC-MS/MS method validated the gravimetric nature of the CCS-qHNMR analytical tandem. Underlying this LC-based cross-validation, comprehensive phytochemical isolation and characterization established 19 single-compound reference standards that represented all ten metabolite classes. Finally, quantum mechanical 1H iterative Full Spin Analysis (HiFSA) of each standard provided a blueprint for future structural dereplication, identification, and quantification of Rhodiola marker constituents. The combination of two gravimetric analytical methods, loss-free CCS and IC-qHNMR, realizes the first chemical standardization of a botanical material that comprehensively captures a metabolome and permits absolute quantification.


Assuntos
Rhodiola , Cromatografia Líquida , Distribuição Contracorrente , Metaboloma , Espectrometria de Massas em Tandem
10.
Talanta ; 234: 122688, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364485

RESUMO

Untargeted metabolomics has been widely used for studies with zebrafish embryos. Until now, the number of analytical approaches to determine metabolites in zebrafish is limited, and there is a lack of consensus on the best platforms for comprehensive metabolomics analysis of zebrafish embryos. In addition, the capacity of these methods to detect metabolites is unsatisfactory and the confidence level for identifying compounds is relatively low. To improve the metabolome coverage, we mainly focused on the optimization of separation mechanisms, mobile phase additives, and resuspension solvents based on liquid chromatography (LC) coupling to high-resolution mass spectrometry (HRMS) techniques. Moreover, the procedures for optimizing methods were assessed when taking metabolite profiles in both positive and negative ionization modes into account. Four LC columns were studied: C18, T3, PFP, and HILIC. In positive ionization mode, it was strongly recommended to employ the HILIC approach operated at the neutral condition, which led to the presence of more than 4700 features and the annotation of 151 metabolites, mainly zwitterionic and basic compounds, in comparison to reverse phase (RP)-based methods with less than 1000 features. In negative ionization mode, the PFP column operated at 0.02% acetic acid showed the best performance in terms of metabolite coverage: 3100 metabolic features were detected and 218 metabolites were annotated in zebrafish embryos. Metabolite profiles mainly contained acidic and zwitterionic compounds. HILIC-based platforms were complementary to RP columns when analyzing highly polar metabolites. Additionally, it was preferable to reconstitute zebrafish extracts in 100% water for analysis of metabolites on RP columns, with a 20-30% increase in the number of identified metabolites compared to a 50% water in methanol solution. However, water/methanol (1:9, v/v), as resuspension solution, was advantageous over water/methanol (1:1, v/v) for HILIC analysis showing an 8-15% increase in detected metabolites. In total 336 polar metabolites were annotated by the combination of the optimized HILIC (positive) and PFP (negative) approaches. The largest metabolome coverage of polar metabolites in zebrafish embryos was obtained when three approaches were combined (negative PFP and HILIC, and HILIC positive) resulting in more than 420 annotated compounds.


Assuntos
Metaboloma , Peixe-Zebra , Animais , Cromatografia Líquida , Metabolômica , Solventes
11.
Reprod Health ; 18(1): 171, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407851

RESUMO

BACKGROUND: Multiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS. METHODS: We identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed. RESULTS: Twenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with myo-inositol + D-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31-93.58]). Myo-inositol + D-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: - 0.72 [95% CI (- 1.11)-(- 0.34)] to - 0.89 [95% CI (- 1.460)-(- 0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events. CONCLUSIONS: Ours is the first study to report that for women with PCOS, myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with D-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registration PROSPERO CRD42020211524.


Assuntos
Berberina , Resistência à Insulina , Metformina , Síndrome do Ovário Policístico , Tiazolidinedionas , Tomada de Decisão Clínica , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Inositol/uso terapêutico , Insulina , Metaboloma , Metformina/uso terapêutico , Metanálise em Rede , Síndrome do Ovário Policístico/tratamento farmacológico , Tiazolidinedionas/uso terapêutico , Incerteza
12.
Cell Rep ; 36(7): 109527, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34348131

RESUMO

COVID-19 pathology involves dysregulation of diverse molecular, cellular, and physiological processes. To expedite integrated and collaborative COVID-19 research, we completed multi-omics analysis of hospitalized COVID-19 patients, including matched analysis of the whole-blood transcriptome, plasma proteomics with two complementary platforms, cytokine profiling, plasma and red blood cell metabolomics, deep immune cell phenotyping by mass cytometry, and clinical data annotation. We refer to this multidimensional dataset as the COVIDome. We then created the COVIDome Explorer, an online researcher portal where the data can be analyzed and visualized in real time. We illustrate herein the use of the COVIDome dataset through a multi-omics analysis of biosignatures associated with C-reactive protein (CRP), an established marker of poor prognosis in COVID-19, revealing associations between CRP levels and damage-associated molecular patterns, depletion of protective serpins, and mitochondrial metabolism dysregulation. We expect that the COVIDome Explorer will rapidly accelerate data sharing, hypothesis testing, and discoveries worldwide.


Assuntos
COVID-19/genética , COVID-19/metabolismo , Bases de Dados Genéticas , Metaboloma , Proteoma , Transcriptoma , Acesso à Informação , Adulto , COVID-19/imunologia , Estudos de Casos e Controles , Mineração de Dados , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Proteômica , Adulto Jovem
14.
BMC Plant Biol ; 21(1): 397, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433413

RESUMO

BACKGROUND: Mandarin 'Shatangju' is susceptible to Huanglongbing (HLB) and the HLB-infected fruits are small, off-flavor, and stay-green at the maturity period. To understand the relationship between pericarp color and HLB pathogen and the effect mechanism of HLB on fruit pericarp coloration, quantitative analyses of HLB bacterial pathogens and carotenoids and also the integrative analysis of metabolome and transcriptome profiles were performed in the mandarin 'Shatangju' variety with four different color fruits, whole green fruits (WGF), top-yellow and base-green fruits (TYBGF), whole light-yellow fruits (WLYF), and whole dark-yellow fruits (WDYF) that were infected with HLB. RESULTS: the HLB bacterial population followed the order WGF > TYBGF > WLYF > WDYF. And there were significant differences between each group of samples. Regarding the accumulation of chlorophyll and carotenoid, the chlorophyll-a content in WGF was the highest and in WDYF was the lowest. The content of chlorophyll-b in WGF was significantly higher than that in other three pericarps. There were significant differences in the total content of carotenoid between each group. WGF and TYBGF pericarps were low in phytoene, γ-carotene, ß-cryptoxanthin and apocarotenal, while other kinds of carotenoids were significantly higher than those in WDYF. And WLYF was only short of apocarotenal. We comprehensively compared the transcriptome and metabolite profiles of abnormal (WGF, TYBGF and WLYF) and normal (WDYF, control) pericarps. In total, 2,880, 2,782 and 1,053 differentially expressed genes (DEGs), including 121, 117 and 43 transcription factors were identified in the three comparisons, respectively. The qRT-PCR confirmed the expression levels of genes selected from transcriptome. Additionally, a total of 77 flavonoids and other phenylpropanoid-derived metabolites were identified in the three comparisons. Most (76.65 %) showed markedly lower abundances in the three comparisons. The phenylpropanoid biosynthesis pathway was the major enrichment pathway in the integrative analysis of metabolome and transcriptome profiles. CONCLUSIONS: Synthesizing the above analytical results, this study indicated that different color pericarps were associated with the reduced levels of some carotenoids and phenylpropanoids derivatives products and the down-regulation of proteins in flavonoids, phenylpropanoids derivatives biosynthesis pathway and the photosynthesis-antenna proteins.


Assuntos
Clorofila/análise , Citrus/genética , Citrus/microbiologia , Flavonoides/análise , Frutas/microbiologia , Interações Hospedeiro-Patógeno , Liberibacter/patogenicidade , Pigmentos Biológicos , Produtos Agrícolas/genética , Produtos Agrícolas/microbiologia , Produtos Agrícolas/fisiologia , Frutas/genética , Frutas/fisiologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Metaboloma , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Transcriptoma
15.
BMC Plant Biol ; 21(1): 396, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433422

RESUMO

BACKGROUND: Bagging can improve the appearance of fruits and increase the food safety and commodification, it also has effects on intrinsic quality of the fruits, which was commonly reported negative changes. Fig can be regarded as a new model fruit with its relatively small genome size and long fruit season. RESULTS: In this study, widely targeted metabolomics based on HPLC MS/MS and RNA-seq of the fruit tissue of the 'Zibao' fig before and after bagging were analyzed to reveal the metabolites changes of the edible part of figs and the underneath gene expression network changes. A total of 771 metabolites were identified in the metabolome analysis using fig female flower tissue. Of these, 88 metabolites (including one carbohydrate, eight organic acids, seven amino acids, and two vitamins) showed significant differences in fruit tissue before and after bagging. Changes in 16 structural genes, 13 MYB transcription factors, and endogenous hormone (ABA, IAA, and GA) metabolism and signal transduction-related genes in the biosynthesis pathway of flavonoids after bagging were analyzed by transcriptome analysis. KEGG enrichment analysis also determined significant differences in flavonoid biosynthesis pathways in female flower tissue before and after bagging. CONCLUSIONS: This work provided comprehensive information on the composition and abundance of metabolites in the female flower tissue of fig. The results showed that the differences in flavor components of the fruit before and after bagging could be explained by changes in the composition and abundance of carbohydrates, organic acids, amino acids, and phenolic compounds. This study provides new insights into the effects of bagging on changes in the intrinsic and appearance quality of fruits.


Assuntos
Ficus/genética , Ficus/metabolismo , Flavonoides/análise , Flavonoides/biossíntese , Flavonoides/genética , Frutas/genética , Frutas/metabolismo , China , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Flores/genética , Flores/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Variação Genética , Genótipo , Metaboloma
16.
Poult Sci ; 100(9): 101315, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34280650

RESUMO

Antibiotic overuse in poultry husbandry poses a potential threat to meat safety and human health. Lauric acid (LA) is a primary medium-chain fatty acid (MCFA) with a strong antibacterial capacity. The goal of this study was to evaluate the beneficial effects of LA on the growth performance, immune responses, serum metabolism, and cecal microbiota of broiler chickens. One-day-old male Ross 308 broilers were randomly divided into 4 groups: CON, fed a basal diet; ANT, a basal diet supplemented with 75 mg/kg antibiotic; LA500, a basal diet supplemented with 500 mg/kg LA; LA1000, a basal diet supplemented with 1000 mg/kg LA. The feeding period was 42 d. The results showed that LA significantly improved broiler growth and immune functions, as evidenced by increased body weight (BW) and average daily gain (ADG), enhanced intestinal mucosal barrier, upregulated immunoglobulins (IgA, IgM, and IgY), and downregulated inflammatory cytokines (IL-1ß, IL-6, TNF-α, IL-4, and IL-10) (P < 0.05). HPLC/MS-based metabolome analysis revealed that the serum metabolites in the LA group differed from those of CON and ANT groups. LA markedly decreased the abundance of phosphatidylcholines (PCs), increased lysophosphatidylcholines (LysoPCs), and inhibited the sphingolipid metabolism pathway, indicating its capacity to modulate lipid metabolism. 16S rRNA sequencing indicated that LA significantly altered cecal microbiota composition by reducing Phascolarctobacterium, Christensenellaceae_R-7_group, and Bacteroides, and increasing Faecalibacterium and Ruminococcaceae_UCG-014 (P < 0.05). Furthermore, Spearman correlation analysis revealed that changes in metabolism and microbiota were highly correlated with the growth and immune indices; strong links were also found between lipid metabolism and microbial composition. Taken together, LA promotes broiler growth and immune functions by regulating lipid metabolism and gut microbiota. The above findings highlight the substantial potential of LA as a supplement in poultry diets and provide a new strategy to reduce antibiotic usage and improve food safety.


Assuntos
Galinhas , Microbioma Gastrointestinal , Ração Animal/análise , Animais , Galinhas/genética , Dieta/veterinária , Suplementos Nutricionais/análise , Ácidos Láuricos , Masculino , Metaboloma , RNA Ribossômico 16S
17.
J Proteome Res ; 20(8): 4010-4021, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34296888

RESUMO

Dried blood spot (DBS) metabolite analysis is a central tool for the clinic, e.g., newborn screening. Instead of applying multiple analytical methods, a single liquid chromatography-mass spectrometry (LC-MS) method was developed for metabolites spanning from highly polar glucose to hydrophobic long-chain acylcarnitines. For liquid chromatography, a diphenyl column and a multi-linear solvent gradient operated at elevated flow rates allowed for an even-spread resolution of diverse metabolites. Injecting moderate volumes of DBS organic extracts directly, in contrast to evaporation and reconstitution, provided substantial increases in analyte recovery. Q Exactive MS settings were also tailored for sensitivity increases, and the method allowed for analyte retention time and peak area repeatabilities of 0.1-0.4 and 2-10%, respectively, for a wide polarity range of metabolites (log P -4.4 to 8.8). The method's performance was suited for both untargeted analysis and targeted approaches evaluated in clinically relevant experiments.


Assuntos
Metaboloma , Metabolômica , Cromatografia Líquida , Teste em Amostras de Sangue Seco , Humanos , Recém-Nascido , Espectrometria de Massas
18.
J Proteome Res ; 20(8): 3992-4000, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34304563

RESUMO

Genes, sex, age, diet, lifestyle, gut microbiome, and multiple other factors affect human metabolomic profiles. Understanding metabolomic variation is critical in human nutrition research as metabolites that are sensitive to change versus those that are more stable might be more informative for a particular study design. This study aims to identify stable metabolomic regions and determine the genetic and environmental contributions to stability. Using a classic twin design, 1H nuclear magnetic resonance (NMR) urinary metabolomic profiles were measured in 128 twins at baseline, 1 month, and 2 months. Multivariate mixed models identified stable urinary metabolites with intraclass correlation coefficients ≥0.51. Longitudinal twin modeling measured the contribution of genetic and environmental influences to variation in the stable urinary NMR metabolome, comprising stable metabolites. The conservation of an individual's stable urinary NMR metabolome over time was assessed by calculating conservation indices. In this study, 20% of the urinary NMR metabolome is stable over 2 months (intraclass correlation (ICC) 0.51-0.65). Common genetic and shared environmental factors contributed to variance in the stable urinary NMR metabolome over time. Using the stable metabolome, 91% of individuals had good metabolomic conservation indices ≥0.70. To conclude, this research identifies 20% of the urinary NMR metabolome as stable, improves our knowledge of the sources of metabolomic variation over time, and demonstrates the conservation of an individual's urinary NMR metabolome.


Assuntos
Microbioma Gastrointestinal , Metaboloma , Dieta , Humanos , Espectroscopia de Ressonância Magnética , Metabolômica
19.
Environ Int ; 156: 106750, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34256302

RESUMO

BACKGROUND: Birthweight is an indicator of fetal growth and environmental-related alterations of birthweight have been linked with multiple disorders and conditions progressing into adulthood. Although a few studies have assessed the association between birthweight and the totality of exogenous exposures and their downstream molecular responses in maternal urine and cord blood; no prior research has considered a) the maternal serum prenatal metabolome, which is enriched for hormones, and b) non-linear and synergistic associations among exposures. METHODS: We measured the maternal serum metabolome during pregnancy using an untargeted metabolomics approach and birthweight for gestational age (BWGA) z-score in 410 mother-child dyads enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort. We leveraged a Bayesian factor analysis for interaction to select the most important metabolites associated with BWGA z-score and to evaluate their linear, non-linear and non-additive associations. We also assessed the primary biological functions of the identified proteins using the MetaboAnalyst, a centralized repository of curated functional information. We compared our findings with those of a traditional metabolite-wide association study (MWAS) in which metabolites are individually associated with BWGA z-score. RESULTS: Among 1110 metabolites, 46 showed evidence of U-shape associations with BWGA z-score. Most of the identified metabolites (85%) were lipids primarily enriched for pathways central to energy production, immune function, and androgen and estrogen metabolism, which are essential for pregnancy and parturition processes. Metabolites within the same class, i.e. steroids and phospholipids, showed synergistic relationships with each other. CONCLUSIONS: Our results support that the aspects of the maternal metabolome during pregnancy contribute linearly, non-linearly and synergistically to variation in newborn birthweight.


Assuntos
Desenvolvimento Fetal , Metaboloma , Adulto , Teorema de Bayes , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez
20.
Nat Commun ; 12(1): 4462, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294718

RESUMO

RORγt+ lymphocytes, including interleukin 17 (IL-17)-producing gamma delta T (γδT17) cells, T helper 17 (Th17) cells, and group 3 innate lymphoid cells (ILC3s), are important immune regulators. Compared to Th17 cells and ILC3s, γδT17 cell metabolism and its role in tissue homeostasis remains poorly understood. Here, we report that the tissue milieu shapes splenic and intestinal γδT17 cell gene signatures. Conditional deletion of mitochondrial transcription factor A (Tfam) in RORγt+ lymphocytes significantly affects systemic γδT17 cell maintenance and reduces ILC3s without affecting Th17 cells in the gut. In vivo deletion of Tfam in RORγt+ lymphocytes, especially in γδT17 cells, results in small intestine tissue remodeling and increases small intestine length by enhancing the type 2 immune responses in mice. Moreover, these mice show dysregulation of the small intestine transcriptome and metabolism with less body weight but enhanced anti-helminth immunity. IL-22, a cytokine produced by RORγt+ lymphocytes inhibits IL-13-induced tuft cell differentiation in vitro, and suppresses the tuft cell-type 2 immune circuit and small intestine lengthening in vivo, highlighting its key role in gut tissue remodeling.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Grupo de Alta Mobilidade/metabolismo , Intestino Delgado/imunologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Animais , Diferenciação Celular , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Feminino , Perfilação da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade/deficiência , Proteínas de Grupo de Alta Mobilidade/genética , Homeostase/imunologia , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Intestino Delgado/citologia , Intestino Delgado/metabolismo , Masculino , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Organoides , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica/metabolismo , Subpopulações de Linfócitos T/citologia , Células Th17/citologia , Células Th17/imunologia , Células Th17/metabolismo
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