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

Roux-en-Y gastric bypass-induced perturbative changes in microbial communities and metabolic pathways in rats

Mon, 28/11/2022 - 12:00
Front Microbiol. 2022 Nov 10;13:1034839. doi: 10.3389/fmicb.2022.1034839. eCollection 2022.ABSTRACTBACKGROUND: Obesity has become a global health and socioeconomic problem because of an inadequate balance between energy intake and energy expenditure. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the two most commonly used strategies for weight loss, which have been proven to benefit from gut microbiota restoration.METHODS: Rats received SG, RYGB, and sham operations for 10 weeks. At the end of the experiment, the fecal microbiota was analyzed using 16s rRNA gene sequencing. In addition, the shift in the plasma metabolism of rats that underwent RYGB surgery was analyzed using untargeted metabolomics. The crosstalk between microbiome and metabolites was revealed using metabolic pathway enrichment and integrated analysis.RESULT: The SG surgery induced a modest shift in the gut microbiota relative to the RYGB. RYGB significantly decreased the alpha diversity and Firmicutes/Bacteroides (F/B) ratio and increased the proportion of Escherichia, Bacteroides, and Akkermansia genera compared to sham and SG operations. The predicted function of gut microbiota revealed that the RYGB surgery uniquely enhanced the capability of linoleic acid and sphingolipid metabolism. Furthermore, the circulating serine, phosphatidylcholine (PC) 20:5/22:5, riboflavin, L-carnitine, and linoleic acid were evaluated after RYGB surgery. In addition, the metabolic pathway enrichment and integrated analysis suggest that the RYGB induced Escherichia, Bacteroides, and Akkermansia might inhibit the sphingonine and phytosphingosine metabolisms from serine and promote the PC (20:5/22:5) metabolism to produce linoleic acid.CONCLUSION: This comprehensive analysis not only revealed the difference in the gut microbiota shifts after SG and RYGB but also discovered the perturbative changes in microbial communities and metabolic pathways after RYGB surgery, which provided clues for improving the beneficial effect of RYGB in metabolic disease intervention via regulating bacterial-metabolite crosstalk.PMID:36439854 | PMC:PMC9685675 | DOI:10.3389/fmicb.2022.1034839

Metabonomics reveals that entomopathogenic nematodes mediate tryptophan metabolites that kill host insects

Mon, 28/11/2022 - 12:00
Front Microbiol. 2022 Nov 10;13:1042145. doi: 10.3389/fmicb.2022.1042145. eCollection 2022.ABSTRACTThe entomopathogenic nematode (EPN) Steinernema feltiae, which carries the symbiotic bacterium Xenorhabdus bovienii in its gut, is an important biocontrol agent. This EPN could produce a suite of complex metabolites and toxin proteins and lead to the death of host insects within 24-48 h. However, few studies have been performed on the key biomarkers released by EPNs to kill host insects. The objective of this study was to examine what substances produced by EPNs cause the death of host insects. We found that all densities of nematode suspensions exhibited insecticidal activities after hemocoelic injection into Galleria mellonella larvae. EPN infection 9 h later led to immunosuppression by activating insect esterase activity, but eventually, the host insect darkened and died. Before insect immunity was activated, we applied a high-resolution mass spectrometry-based metabolomics approach to determine the hemolymph of the wax moth G. mellonella infected by EPNs. The results indicated that the tryptophan (Trp) pathway of G. mellonella was significantly activated, and the contents of kynurenine (Kyn) and 3-hydroxyanthranilic acid (3-HAA) were markedly increased. Additionally, 3-HAA was highly toxic to G. mellonella and resulted in corrected mortalities of 62.50%. Tryptophan metabolites produced by EPNs are a potential marker to kill insects, opening up a novel line of inquiry into exploring the infestation mechanism of EPNs.PMID:36439848 | PMC:PMC9686292 | DOI:10.3389/fmicb.2022.1042145

Vancomycin-induced gut microbiota dysbiosis aggravates allergic rhinitis in mice by altered short-chain fatty acids

Mon, 28/11/2022 - 12:00
Front Microbiol. 2022 Nov 1;13:1002084. doi: 10.3389/fmicb.2022.1002084. eCollection 2022.ABSTRACTOBJECTIVE: This study aims to explore how gut microbiota dysbiosis affects allergic rhinitis (AR) and whether short-chain fatty acids (SCFAs) play a role in this process.METHODS: A mouse gut microbiota dysbiosis model was established by adding vancomycin to drinking water for 2 weeks before ovalbumin (OVA) sensitization. Then an OVA-alum AR mouse model was established by intraperitoneal OVA injection followed by nasal excitation. Hematoxylin and eosin (H&E) staining was performed to observe pathological changes in nasal and colon tissues of AR mice. Serum levels of total-IgE, OVA-sIgE, IL-4, IL-5, IL-10, and TGF-β1 were measured. The composition and diversity of the mouse gut microbiota were observed by 16S rDNA sequencing. Levels of SCFAs in feces were determined using SCFA-targeted metabolomics. Sodium butyrate (NaB) was added daily to mice on a low-fiber basal diet 2 weeks before the first sensitization, until the end of the study.RESULTS: After gut microbiota dysbiosis, serum levels of the total IgE, OVA-sIgE, IL-4, and IL-5 in AR mice were significantly increased, compared with the control group. The composition and diversity of gut microbiota were significantly altered after gut microbiota dysbiosis, with the fecal SCFAs significantly reduced as well. The reduced bacterial genera after gut microbiota dysbiosis, such as Ruminococcus and Lactobacillus, were significantly and positively correlated with SCFAs. In contrast, the increased genera in the Van group, such as Escherichia-Shigella and Klebsiella, were significantly negatively correlated with SCFAs in feces. NaB treatment significantly reduced total-IgE, OVA-sIgE, IL-4, and IL-5 levels in serum, and inflammatory infiltration of the nasal and colon mucosa. In addition, serum levels of IL-10 and TGF-β1 increased significantly after NaB treatment. Foxp3 protein in the colon was upregulated considerably after NaB intervention.CONCLUSION: Vancomycin-induced gut microbiota dysbiosis increased susceptibility and severity of AR, which is significantly related to reduced SCFA-producing bacteria, fecal SCFAs, and specific bacterial taxa. In addition, it was found that NaB alleviated low dietary fiber base-fed symptoms and immune status in AR mice.PMID:36439824 | PMC:PMC9687373 | DOI:10.3389/fmicb.2022.1002084

The impact of dietary fibers on <em>Clostridioides difficile</em> infection in a mouse model

Mon, 28/11/2022 - 12:00
Front Cell Infect Microbiol. 2022 Nov 9;12:1028267. doi: 10.3389/fcimb.2022.1028267. eCollection 2022.ABSTRACTDiets rich in fiber may provide health benefits and regulate the gut microbiome, which affects the immune system. However, the role of dietary fiber in Clostridioides difficile infection (CDI) is controversial. Here, we investigated the use of fermentable fibers, such as inulin or pectin, to replace the insoluble fiber cellulose to explore how dietary fiber affects C. difficile-induced colitis in mice through intestinal microecology and metabolomics. Using C. difficile VPI 10463, we generated a mouse model of antibiotic-induced CDI. We evaluated disease outcomes and the microbial community among mice fed two fermentable fibers (inulin or pectin) versus the insoluble fiber cellulose. We analyzed and compared the gut microbiota, intestinal epithelium, cytokine levels, immune responses, and metabolites between the groups. Severe histological injury and elevated cytokine levels were observed in colon tissues after infection. Different diets showed different effects, and pectin administration protected intestinal epithelial permeability. Pectin also steadily increased the diversity of the microbiome and decreased the levels of C. difficile-induced markers of inflammation in serum and colonic tissues. The pectin group showed a higher abundance of Lachnospiraceae and a lower abundance of the conditionally pathogenic Enterobacteriaceae than the cellulose group with infection. The concentration of short-chain fatty acids in the cecal contents was also higher in the pectin group than in the cellulose group. Pectin exerted its effects through the aryl hydrocarbon receptor (AhR) pathway, which was confirmed by using the AhR agonist FICZ and the inhibitor CH2223191. Our results show that pectin alters the microbiome and metabolic function and triggers a protective immune response.PMID:36439215 | PMC:PMC9682084 | DOI:10.3389/fcimb.2022.1028267

Update on gut microbiota in cardiovascular diseases

Mon, 28/11/2022 - 12:00
Front Cell Infect Microbiol. 2022 Nov 10;12:1059349. doi: 10.3389/fcimb.2022.1059349. eCollection 2022.ABSTRACTIn recent years, due to the development and widespread utilization of metagenomic sequencing and metabolomics, the relationship between gut microbiota and human cardiovascular diseases (CVDs) has received extensive attention. A growing number of studies have shown a strong relationship between gut microbiota and CVDs, such as coronary atherosclerosis, hypertension (HTN) and heart failure (HF). It has also been revealed that intestinal flora-related metabolites, such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFA) and bile acids (BAs), are also related to the development, prevention, treatment and prognosis of CVDs. In this review, we presented and summarized the recent findings on the relationship between gut microbiota and CVDs, and concluded several currently known gut microbiota-related metabolites and the occurrence and development of CVDs.PMID:36439214 | PMC:PMC9684171 | DOI:10.3389/fcimb.2022.1059349

<em>Buyang Huanwu</em> decoction affects gut microbiota and lipid metabolism in a ZDF rat model of co-morbid type 2 diabetes mellitus and obesity: An integrated metabolomics analysis

Mon, 28/11/2022 - 12:00
Front Chem. 2022 Nov 9;10:1036380. doi: 10.3389/fchem.2022.1036380. eCollection 2022.ABSTRACTType 2 diabetes mellitus (T2DM) is a chronic disease associated with many severe complications such as blindness, amputation, renal failure, and cardiovascular disease. Currently, the prevention and treatment of T2DM is a major global challenge as the number of aging and obese people is increasing. Traditional Chinese medicine offers the advantages of multi-target holistic and individual treatment for obesity and type 2 diabetes. However, most of the TCMs for T2DM are not scientifically evaluated. Here, Buyang Huanwu decoction (BYHWD), a widely used TCM formula, was used to explore scientific pharmacological activity against T2DM in rat models. First, BYHWD exhibited excellent inhibitory actions against body fat accumulation and increased blood triglyceride levels, and a high-fat diet (HFD) induced blood glucose elevation in diabetic rats. Moreover, 16S rDNA sequencing of fecal samples identified the distinct changes in the community composition of gut flora following BYHWD treatment, displayed as significantly increased Bacteroidetes and dramatically decreased Firmicutes at the phyla level, and the remarkable increase in the abundance of Lactobacillus and Blautia. Additionally, lipid metabolomics based on liquid chromatography-mass spectrometry revealed a significant shift of lipid metabolites in the liver after BYHWD treatment. Notably, these differential lipid metabolites were particularly involved in biological processes such as cholesterol metabolism, linoleic acid metabolism, glycerolipid metabolism, glycerophospholipid metabolism, insulin resistance, arachidonic acid metabolism, and alpha-linoleic acid metabolism. Importantly, Spearman correlation analyses suggested an association between disturbed gut microbiota and altered lipid metabolites. Moreover, they were also closely associated with the bioactivities of BYHWD to reduce the blood lipid and blood glucose levels. Collectively, these results suggest that BYHWD could meliorate gut microbiota dysbiosis and lipid metabolite alterations induced by the HFD in diabetic rats. These results not only provide a novel perspective on understanding the mechanisms underlying BYHWD bioactivity against T2DM but also suggest the use of advanced systems biology methods to reveal some unknown scientific laws in TCM theories.PMID:36438869 | PMC:PMC9682010 | DOI:10.3389/fchem.2022.1036380

Metabolomics-driven strain improvement: A mini review

Mon, 28/11/2022 - 12:00
Front Mol Biosci. 2022 Nov 9;9:1057709. doi: 10.3389/fmolb.2022.1057709. eCollection 2022.ABSTRACTIn recent years, mass spectrometry-based metabolomics has been established as a powerful and versatile technique for studying cellular metabolism by comprehensive analysis of metabolites in the cell. Although there are many scientific reports on the use of metabolomics for the elucidation of mechanism and physiological changes occurring in the cell, there are surprisingly very few reports on its use for the identification of rate-limiting steps in a synthetic biological system that can lead to the actual improvement of the host organism. In this mini review, we discuss different strategies for improving strain performance using metabolomics data and compare the application of metabolomics-driven strain improvement techniques in different host microorganisms. Finally, we highlight several success stories on the use of metabolomics-driven strain improvement strategies, which led to significant bioproductivity improvements.PMID:36438656 | PMC:PMC9681786 | DOI:10.3389/fmolb.2022.1057709

An anchored experimental design and meta-analysis approach to address batch effects in large-scale metabolomics

Mon, 28/11/2022 - 12:00
Front Mol Biosci. 2022 Nov 9;9:930204. doi: 10.3389/fmolb.2022.930204. eCollection 2022.ABSTRACTUntargeted metabolomics studies are unbiased but identifying the same feature across studies is complicated by environmental variation, batch effects, and instrument variability. Ideally, several studies that assay the same set of metabolic features would be used to select recurring features to pursue for identification. Here, we developed an anchored experimental design. This generalizable approach enabled us to integrate three genetic studies consisting of 14 test strains of Caenorhabditis elegans prior to the compound identification process. An anchor strain, PD1074, was included in every sample collection, resulting in a large set of biological replicates of a genetically identical strain that anchored each study. This enables us to estimate treatment effects within each batch and apply straightforward meta-analytic approaches to combine treatment effects across batches without the need for estimation of batch effects and complex normalization strategies. We collected 104 test samples for three genetic studies across six batches to produce five analytical datasets from two complementary technologies commonly used in untargeted metabolomics. Here, we use the model system C. elegans to demonstrate that an augmented design combined with experimental blocks and other metabolomic QC approaches can be used to anchor studies and enable comparisons of stable spectral features across time without the need for compound identification. This approach is generalizable to systems where the same genotype can be assayed in multiple environments and provides biologically relevant features for downstream compound identification efforts. All methods are included in the newest release of the publicly available SECIMTools based on the open-source Galaxy platform.PMID:36438654 | PMC:PMC9682135 | DOI:10.3389/fmolb.2022.930204

<em>Inventa</em>: A computational tool to discover structural novelty in natural extracts libraries

Mon, 28/11/2022 - 12:00
Front Mol Biosci. 2022 Nov 11;9:1028334. doi: 10.3389/fmolb.2022.1028334. eCollection 2022.ABSTRACTCollections of natural extracts hold potential for the discovery of novel natural products with original modes of action. The prioritization of extracts from collections remains challenging due to the lack of a workflow that combines multiple-source information to facilitate the data interpretation. Results from different analytical techniques and literature reports need to be organized, processed, and interpreted to enable optimal decision-making for extracts prioritization. Here, we introduce Inventa, a computational tool that highlights the structural novelty potential within extracts, considering untargeted mass spectrometry data, spectral annotation, and literature reports. Based on this information, Inventa calculates multiple scores that inform their structural potential. Thus, Inventa has the potential to accelerate new natural products discovery. Inventa was applied to a set of plants from the Celastraceae family as a proof of concept. The Pristimera indica (Willd.) A.C.Sm roots extract was highlighted as a promising source of potentially novel compounds. Its phytochemical investigation resulted in the isolation and de novo characterization of thirteen new dihydro-β-agarofuran sesquiterpenes, five of them presenting a new 9-oxodihydro-β-agarofuran base scaffold.PMID:36438653 | PMC:PMC9692083 | DOI:10.3389/fmolb.2022.1028334

Integration of multi-omics technologies for crop improvement: Status and prospects

Mon, 28/11/2022 - 12:00
Front Bioinform. 2022 Oct 19;2:1027457. doi: 10.3389/fbinf.2022.1027457. eCollection 2022.ABSTRACTWith the rapid development of next-generation sequencing (NGS), multi-omics techniques have been emerging as effective approaches for crop improvement. Here, we focus mainly on addressing the current status and future perspectives toward omics-related technologies and bioinformatic resources with potential applications in crop breeding. Using a large amount of omics-level data from the functional genome, transcriptome, proteome, epigenome, metabolome, and microbiome, clarifying the interaction between gene and phenotype formation will become possible. The integration of multi-omics datasets with pan-omics platforms and systems biology could predict the complex traits of crops and elucidate the regulatory networks for genetic improvement. Different scales of trait predictions and decision-making models will facilitate crop breeding more intelligent. Potential challenges that integrate the multi-omics data with studies of gene function and their network to efficiently select desirable agronomic traits are discussed by proposing some cutting-edge breeding strategies for crop improvement. Multi-omics-integrated approaches together with other artificial intelligence techniques will contribute to broadening and deepening our knowledge of crop precision breeding, resulting in speeding up the breeding process.PMID:36438626 | PMC:PMC9689701 | DOI:10.3389/fbinf.2022.1027457

<em>SmDXS5</em>, acting as a molecular valve, plays a key regulatory role in the primary and secondary metabolism of tanshinones in <em>Salvia miltiorrhiza</em>

Mon, 28/11/2022 - 12:00
Front Plant Sci. 2022 Nov 10;13:1043761. doi: 10.3389/fpls.2022.1043761. eCollection 2022.ABSTRACTRed sage, the dry root and rhizome of the herbaceous plant Salvia miltiorrhiza Bunge, is widely used for treating various diseases. The low content of tanshinones (terpenoids) has always restricted development of the S. miltiorrhiza industry. Here, we found that SmDXS5, a rate-limiting enzyme-coding gene located at the intersection of primary and secondary metabolism, can effectively change the transcription level and secondary metabolome profile of hairy roots of S. miltiorrhiza, and significantly increase the content of tanshinones. Agrobacterium rhizogenes was used to infuse S. miltiorrhiza explants, and hairy roots of S. miltiorrhiza expressing the SmDXS5 gene were obtained successfully. We identified 39 differentially accumulated metabolites (DAMs) by metabolomics based on ultra-high performance liquid chromatography quadrupole exactive mass spectrometry and multivariate statistics. These DAMs might be key metabolites of SmDXS5 gene regulation. RNA sequencing was used to compare gene expression between the hairy roots of the SmDXS5 overexpressing group and the blank control (BC) group. Compared with the BC group, 18,646 differentially expressed genes were obtained: 8994 were upregulated and 9,652 downregulated. The combined transcriptome and metabolome analyses revealed that the mevalonate and methylerythritol phosphate pathways and synthase gene expression levels in the SmDXS5 overexpressing group were upregulated significantly, and the accumulation of tanshinone components was increased significantly, which promoted the process of glycolysis and promoted the transformation of carbohydrates to secondary metabolism. Moreover, the expression of SmPAL, the first rate-limiting enzyme gene of the phenylpropane pathway, decreased, reducing the accumulation of phenolic acid, another secondary metabolite. Therefore, SmDXS5 can be defined as a 'valve' gene, mainly responsible for regulating the distribution of primary and secondary metabolic flow of tanshinones in S. miltiorrhiza, and for other secondary metabolic pathways. The discovery of SmDXS5 and its molecular valve function in regulating primary and secondary metabolism will provide a basis for the industrial production of tanshinone components, and cultivation of high quality S. miltiorrhiza.PMID:36438137 | PMC:PMC9685628 | DOI:10.3389/fpls.2022.1043761

Biostimulation can prime elicitor induced resistance of grapevine leaves to downy mildew

Mon, 28/11/2022 - 12:00
Front Plant Sci. 2022 Nov 9;13:998273. doi: 10.3389/fpls.2022.998273. eCollection 2022.ABSTRACTUsing plant defense elicitors to protect crops against diseases is an attractive strategy to reduce chemical pesticide use. However, development of elicitors remains limited because of variable effectiveness in the field. In contrast to fungicides that directly target pathogens, elicitors activate plant immunity, which depends on plant physiological status. Other products, the biostimulants, can improve certain functions of plants. In this study, the objective was to determine whether a biostimulant via effects on grapevine physiology could increase effectiveness of a defense elicitor. A new methodology was developed to study biostimulant activity under controlled conditions using in vitro plantlets. Both biostimulant and defense elicitor used in the study were plant extracts. When added to the culture medium, the biostimulant accelerated the beginning of plantlet growth and affected the shoot and root development. It also modified metabolomes and phytohormone contents of leaves, stems, and roots. When applied on shoots, the defense elicitor changed metabolite and phytohormone contents, but effects were different depending on whether plantlets were biostimulated or controls. Defense responses and protection against Plasmopara viticola (downy mildew agent) were induced only for plantlets previously treated with the biostimulant, Therefore, the biostimulant may act by priming the defense elicitor action. In this study, a new method to screen biostimulants active on grapevine vegetative growth was used to demonstrate that a biostimulant can optimize the efficiency of a plant defense elicitor.PMID:36438082 | PMC:PMC9682252 | DOI:10.3389/fpls.2022.998273

Effects of tofacitinib therapy on arginine and methionine metabolites in association with vascular pathophysiology in rheumatoid arthritis: A metabolomic approach

Mon, 28/11/2022 - 12:00
Front Med (Lausanne). 2022 Nov 10;9:1011734. doi: 10.3389/fmed.2022.1011734. eCollection 2022.ABSTRACTINTRODUCTION: Rheumatoid arthritis (RA) has been associated with changes in lipid, arginine and NO metabolism with increased cardiovascular (CV) risk. The aim of this study is to evaluate the effect of tofacitinib, a Janus kinase (JAK) inhibitor, on arginine and methionine metabolism in correlation with inflammation, functional and pathological vascular changes during one-year treatment of patients with RA.MATERIALS AND METHODS: Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound at baseline and after 6 and 12 months. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels at these time points.RESULTS: Twenty-six patients (13 on each arm) completed the study. CRP, ESR and DAS28 decreased significantly during one-year treatment with tofacitinib. Arginine and ADMA showed a negative univariate correlation with CRP but not with FMD, PWV or IMT. Tofacitinib at 10 mg bid significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. ADMA and SDMA levels did not change in our study. Methionine showed negative correlation with FMD at baseline and positive correlation with PWV after 12 months. No change was observed in FMD and PWV but a significant increase was measured in IMT at 6 and 12 months. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with anti-CCP after one-year treatment. With respect to vascular pathophysiology, only PWV and methionine correlated with each other.CONCLUSION: One-year tofacitinib treatment suppressed systemic inflammation and improved functional status in RA. FMD, PWV have not been affected by one-year tofacitinib treatment., while IMT increased further despite treatment. Increased arginine and methionine might contribute to the anti-inflammatory effects of tofacitinib. Increased arginine availability with no changing ADMA may protect FMD and PWV from deterioration. The increase of IMT in the anti-inflammatory environment cannot be explained by arginine or methionine metabolism in this study.PMID:36438060 | PMC:PMC9684209 | DOI:10.3389/fmed.2022.1011734

Targeted metabolomics reveals fatty acid abundance adjustments as playing a crucial role in drought-stress response and post-drought recovery in wheat

Mon, 28/11/2022 - 12:00
Front Genet. 2022 Nov 10;13:972696. doi: 10.3389/fgene.2022.972696. eCollection 2022.ABSTRACTDrought stress is one of the abiotic stresses restricting plant development, reproductive growth, and survival. In the present study, the effect of drought stress and post-drought recovery for the selected local wheat cultivar, Atta Habib, was studied. Wheat was grown for 16 days followed by drought stress for 7 days and allowed to recover for 7 days after the removal of the drought stress. Same-aged untreated plants were also grown as a control. The effect of drought stress and post-drought recovery on morphology (root length, shoot length, root weight, and shoot weight), enzymatic activity, and fatty acid profile were analyzed. The results showed that shoot weight (93.1 mg), root weight (85.2 mg), and shoot length (11.1 cm) decreased in the stressed plants but increased steadily in the recovered plants compared to the same-aged control plants, while root length showed a higher increase (14.0 cm) during drought stress and tended to normalize during the recovery phase (13.4 cm). The ascorbate peroxidase activity increased in the stressed plants (5.44 unit/mg protein) compared to the control, while gradually normalizing in the recovery phase (5.41 unit/mg protein). Gas chromatography coupled mass spectrometric analysis revealed abundance changes in important fatty acids, such as palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid. Palmitic acid (39.1%) and oleic acid (2.11%) increased in the drought-stressed plants, while a reduction in linoleic acid (6.85%) and linolenic acid (51.18%) was observed compared to the same-aged control plants, i.e., palmitic (33.71%), oleic (0.95%), linoleic (7.52%), and linolenic acid (55.23%). The results suggest that wheat tries to recover in the post-drought stage by repairing oxidative damage through ascorbate peroxidase, and by adjusting fatty acid abundances under drought stress and during the post-drought phase in an effort to maintain membranes' integrity and a suitable fat metabolism route, thus helping recovery. Targeted metabolomics may be further used to explore the role of other metabolites in the drought-stress response mechanism in wheat. Furthermore, this relatively little explored avenue of post-drought recovery needs more detailed studies involving multiple stress durations.PMID:36437965 | PMC:PMC9691424 | DOI:10.3389/fgene.2022.972696

Examining the effects of <em>Salmonella</em> phage on the caecal microbiota and metabolome features in <em>Salmonella</em>-free broilers

Mon, 28/11/2022 - 12:00
Front Genet. 2022 Nov 10;13:1060713. doi: 10.3389/fgene.2022.1060713. eCollection 2022.ABSTRACTBacteriophages selectively infect and kill their target bacterial host, being a promising approach to controlling zoonotic bacteria in poultry production. To ensure confidence in its use, fundamental questions of safety and toxicity monitoring of phage therapy should be raised. Due to its high specificity, a minimal impact on the gut ecology is expected; however, more in-depth research into key parameters that influence the success of phage interventions has been needed to reach a consensus on the impact of bacteriophage therapy in the gut. In this context, this study aimed to investigate the interaction of phages with animals; more specifically, we compared the caecum microbiome and metabolome after a Salmonella phage challenge in Salmonella-free broilers, evaluating the role of the phage administration route. To this end, we employed 45 caecum content samples from a previous study where Salmonella phages were administered via drinking water or feed for 24 h from 4, 5 to 6-weeks-old broilers. High-throughput 16S rRNA gene sequencing showed a high level of similarity (beta diversity) but revealed a significant change in alpha diversity between broilers with Salmonella-phage administered in the drinking water and control. Our results showed that the phages affected only a few genera of the microbiota's structure, regardless of the administration route. Among these, we found a significant increase in Streptococcus and Sellimonas in the drinking water and Lactobacillus, Anaeroplasma and Clostridia_vadinBB60_group in the feed. Nevertheless, the LC-HRMS-based metabolomics analyses revealed that despite few genera were significantly affected, a substantial number of metabolites, especially in the phage administered in the drinking water were significantly altered (64 and 14 in the drinking water and feed groups, respectively). Overall, our study shows that preventive therapy with bacteriophages minimally alters the caecal microbiota but significantly impacts their metabolites, regardless of the route of administration.PMID:36437955 | PMC:PMC9691336 | DOI:10.3389/fgene.2022.1060713

Comparisons of constitutive resistances to soybean cyst nematode between PI 88788- and Peking-type sources of resistance in soybean by transcriptomic and metabolomic profilings

Mon, 28/11/2022 - 12:00
Front Genet. 2022 Nov 10;13:1055867. doi: 10.3389/fgene.2022.1055867. eCollection 2022.ABSTRACTSoybean cyst nematode (SCN) is a serious damaging disease in soybean worldwide. Peking- and PI 88788-type sources of resistance are two most important germplasm used in breeding resistant soybean cultivars against this disease. However, until now, no comparisons of constitutive resistances to soybean cyst nematode between these two types of sources had been conducted, probably due to the influences of different backgrounds. In this study, we used pooled-sample analysis strategy to minimize the influence of different backgrounds and directly compared the molecular mechanisms underlying constitutive resistance to soybean cyst nematode between these two types of sources via transcriptomic and metabolomic profilings. Six resistant soybean accessions that have identical haplotypes as Peking at Rgh1 and Rhg4 loci were pooled to represent Peking-type sources. The PI88788-type and control pools were also constructed in a same way. Through transcriptomic and metabolomics anaylses, differentially expressed genes and metabolites were identified. The molecular pathways involved in the metabolism of toxic metabolites were predicted to play important roles in conferring soybean cyst nematode resistance to soybean. Functions of two resistant candidate genes were confirmed by hairy roots transformation methods in soybean. Our studies can be helpful for soybean scientists to further learn about the molecular mechanism of resistance to soybean cyst nematode in soybean.PMID:36437927 | PMC:PMC9686325 | DOI:10.3389/fgene.2022.1055867

Multiomics data analysis workflow to assess severity in longitudinal plasma samples of COVID-19 patients

Mon, 28/11/2022 - 12:00
Data Brief. 2022 Nov 22:108765. doi: 10.1016/j.dib.2022.108765. Online ahead of print.ABSTRACTElucidation of molecular markers related to the mounted immune response is crucial for the understanding of disease pathogenesis. In this article, we present the mass-spectrometry-based metabolomic and proteomic data of blood plasma of COVID-19 patients collected at two-time points, which showed a transition from non-severe to severe conditions during these time points. Metabolites were extracted and subjected to mass spectrometric analysis using the Q-Exactive mass spectrometer. For proteomic analysis, depleted plasma samples were tryptic digested and subjected to mass spectrometry analysis. The expression of a few significant targeted proteins was also validated by employing the targeted proteomic approach of multiple reaction monitoring (MRM). Integrative pathway analysis was performed with the significant proteins to obtain biological insights into disease severity. For discussion and more information on the dataset creation, please refer to the related full-length article (Suvarna et al., 2021).PMID:36437893 | PMC:PMC9678393 | DOI:10.1016/j.dib.2022.108765

Pyridoxal 5'-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring

Mon, 28/11/2022 - 12:00
Environ Sci Ecotechnol. 2022 Nov 14;13:100224. doi: 10.1016/j.ese.2022.100224. eCollection 2023 Jan.ABSTRACTPyridaben (PY) is a widely used organochlorine acaricide, which can be detected in the peripheral blood of pregnant women. Available evidence suggests that PY has reproductive toxicity. However, it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring. Here, we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg-1 day-1 via gavage and observed anxiety-like behaviors in PY offspring aged five weeks. We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism. Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected, and the pyridoxal 5'-phosphate (PLP) concentration and the active form of vitamin B6 was significantly reduced. Moreover, the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated. Meanwhile, there was a decreasing trend in the concentration of GABA in the hippocampal DG region. Next, we supplemented PLP at a dose of 20 mg kg-1 day-1 to the PY offspring via intraperitoneal injection at three weeks. We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors. This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism, reduce the concentration of PLP, down-regulate the expression levels of Pdxk and Gad1, inhibit the production of GABA, and ultimately lead to anxiety-like behaviors in offspring.PMID:36437888 | PMC:PMC9691908 | DOI:10.1016/j.ese.2022.100224

Chemicolome and Metabolome Profiling of Xieriga-4 Decoction, A Traditional Mongolian Medicine, Using the UPLC-QTOF/MS Approach

Mon, 28/11/2022 - 12:00
Evid Based Complement Alternat Med. 2022 Nov 16;2022:8197364. doi: 10.1155/2022/8197364. eCollection 2022.ABSTRACTBACKGROUND: Xieriga-4 decoction (XRG-4) is a classic prescription Mongolian medicine that has potent diuretic and anti-inflammatory activities. However, its functional components remain unknown.PURPOSE: This study aimed to identify the chemical components in XRG-4 and its metabolome in vivo.METHODS: An ultra-performance liquid chromatography coupled with a quadrupole time-of-flight tandem mass spectrometry based approach was proposed to systematically profile the chemicolome and metabolome of XRG-4.RESULT: A total of 106 constituents were identified in XRG-4. Eighty-nine components were identified in biological samples, including 78 in urine (24 prototypes and 54 metabolites), 26 in feces (19 prototypes and 7 metabolites), and 9 in plasma (5 prototypes and 4 metabolites). In other tissues, only a few compounds, including alkaloids and iridoids, were detected.CONCLUSION: This comprehensive investigation of the chemical and metabolic profiles of XRG-4 provides a scientific foundation for its quality control and administration of clinically-safe medication.PMID:36437832 | PMC:PMC9683986 | DOI:10.1155/2022/8197364

Combination of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and network pharmacology to reveal the mechanism of Shengyu Decoction for treating anemia

Mon, 28/11/2022 - 12:00
J Sep Sci. 2022 Nov 28. doi: 10.1002/jssc.202200678. Online ahead of print.ABSTRACTAnemia is a common clinical hematological disease with a high incidence, which seriously affects human health. Shengyu Decoction is often used in the treatment of anemia. However, pharmacodynamic substance basis and therapeutic mechanism are still unclear, which hinders the comprehensive development and utilization of Shengyu Decoction. In this study, 143 compounds were identified in Shengyu Decoction using high-throughput ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, 24 of which were absorbed into blood. Taking these blood entering ingredients as the research object, we found through network pharmacology research that ferulic acid, calycosin and astragaloside A can act on AKT1, MAPK1 and MAPK14, and play a role in treating anemia through PI3K-Akt signaling pathway and Pathways in cancer. Finally, it was demonstrated that the active compound could bind to the core target with good affinity by molecular docking. The research shows that Shengyu Decoction has multi-component, multi-target and multi-channel effects in the treatment of anemia, which provides a basis for the development and clinical application of Shengyu Decoction. This article is protected by copyright. All rights reserved.PMID:36437813 | DOI:10.1002/jssc.202200678

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