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

Impacts of seasonal temperatures, ocean warming and marine heatwaves on the nutritional quality of eastern school prawns (Metapenaeus macleayi)

Sat, 11/03/2023 - 12:00
Sci Total Environ. 2023 Mar 9:162778. doi: 10.1016/j.scitotenv.2023.162778. Online ahead of print.ABSTRACTOcean warming and marine heatwaves significantly alter environmental conditions in marine and estuarine environments. Despite their potential global importance for nutrient security and human health, it is not well understood how thermal impacts could alter the nutritional quality of harvested marine resources. We tested whether short-term experimental exposure to seasonal temperatures, projected ocean-warming temperatures, and marine heatwaves affected the nutritional quality of the eastern school prawn (Metapenaeus macleayi). In addition, we tested whether nutritional quality was affected by the duration of exposure to warm temperatures. We show the nutritional quality of M. macleayi is likely to be resilient to short- (28 d), but not longer-term (56 d) exposure to warming temperatures. The proximate, fatty acid and metabolite compositions of M. macleayi were unchanged after 28 d exposure to simulated ocean warming and marine heatwaves. The ocean-warming scenario did, however, show potential for elevated sulphur, iron and silver levels after 28d. Decreasing saturation of fatty acids in M. macleayi after 28 d exposure to cooler temperatures indicates homeoviscous adaptation to seasonal changes. We found that 11 % of measured response variables were significantly different between 28 and 56 d when exposed to the same treatment, indicating the duration of exposure time and time of sampling are critical when measuring this species' nutritional response. Further, we found that future acute warming events could reduce harvestable biomass, despite survivors retaining their nutritional quality. Developing a combined knowledge of the variability in seafood nutrient content with shifts in the availability of harvested seafood is crucial for understanding seafood-derived nutrient security in a changing climate.PMID:36906039 | DOI:10.1016/j.scitotenv.2023.162778

Oral Administration of Nanoformulated Indoximod Ameliorates Ulcerative Colitis by Promoting Mitochondrial Function and Mucosal Healing

Sat, 11/03/2023 - 12:00
Int J Pharm. 2023 Mar 9:122813. doi: 10.1016/j.ijpharm.2023.122813. Online ahead of print.ABSTRACTUlcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with serious mucosal inflammation mainly in the colon and rectum. Currently, there is no effective therapeutics for UC. Indoximod (IND) is a water-insoluble inhibitor for indolamine 2, 3-dioxygenase (IDO) and has been mainly reported in cancer therapy. Here, we prepared orally administrated IND nanoparticles (IND-NPs) for UC treatment and investigated their functions and mechanisms in cellular and animal inflammatory models. Confocal imaging demonstrated that IND-NPs maintained the expression level of ZO-1, Occludin and E-cadherin, thereby stabilizing of intercellular junction in Caco-2 cells. It was found that IND-NPs could lower the ROS level and increase mitochondrial membrane potential as well as ATP level, indicating that IND-NPs could restore DSS-induced mitochondrial dysfunction. In the mice model with DSS-induced colitis, IND-NPs were found to alleviate UC-associated symptoms, inhibit inflammatory response, and improve the integrity of epithelial barrier. The untargeted metabolomics analysis validated that IND-NPs also contributed to regulate the metabolite levels to normal. As an agonist of aryl hydrocarbon receptor (AhR), IND-NPs might repair mucosa via the AhR pathway. These findings demonstrated that IND-NPs prominently ameliorated DSS-induced colonic injury and inflammation and preserved intestinal barrier integrity, showing a promising potential in UC treatment.PMID:36905975 | DOI:10.1016/j.ijpharm.2023.122813

Trade-off of abiotic stress response in floating macrophytes as affected by nanoplastic enrichment

Sat, 11/03/2023 - 12:00
J Hazard Mater. 2023 Mar 4;451:131140. doi: 10.1016/j.jhazmat.2023.131140. Online ahead of print.ABSTRACTNanoparticles have been found in large-scale environmental media in recent years, causing toxic effects in various organisms and even humans through food chain transmission. The ecotoxicological impact of microplastics on specific organisms is currently receiving much attention. However, relatively little research to date has examined the mechanisms through which nanoplastic residue may exert an interference effect on floating macrophytes in constructed wetlands. In our study, the aquatic plant Eichhornia crassipes was subjected to 100 nm polystyrene nanoplastics at concentrations of 0.1, 1 and 10 mg L-1 after 28 days of exposure. E. crassipes can decrease the concentration of nanoplastics in water by 61.42∼90.81% through phytostabilization. The abiotic stress of nanoplastics on the phenotypic plasticity (morphological and photosynthetic properties and antioxidant systems as well as molecular metabolism) of E. crassipes was assessed. The presence of nanoplastics reduced the biomass (10.66%∼22.05%), and the functional organ (petiole) diameters of E. crassipes decreased by 7.38%. The photosynthetic efficiency was determined, showing that the photosynthetic systems of E. crassipes are very sensitive to stress by nanoplastics at a concentration of 10 mg L-1. Oxidative stress and imbalance of antioxidant systems in functional organs are associated with multiple pressure modes from nanoplastic concentrations. The catalase contents of roots increased by 151.19% in the 10 mg L-1 treatment groups compared with the control group. Moreover, 10 mg L-1 concentrations of the nanoplastic pollutant interfere with purine and lysine metabolism in the root system. The hypoxanthine content was reduced by 6.58∼8.32% under exposure to different concentrations of nanoplastics. In the pentose phosphate pathway, the phosphoric acid content was decreased by 32.70% at 10 mg L-1 PS-NPs. In the pentose phosphate pathway, the phosphoric acid content was decreased by 32.70% at 10 mg L-1 PS-NPs. Nanoplastics disturb the efficiency of water purification by floating macrophytes, which reduces the chemical oxygen demand (COD) removal efficiency (from 73% to 31.33%) due to various abiotic stresses. This study provided important information for further clarifying the impact of nanoplastics on the stress response of floating macrophytes.PMID:36905907 | DOI:10.1016/j.jhazmat.2023.131140

Shengjiang Xiexin Decoction ameliorates antibiotic-associated diarrhea by altering the gut microbiota and intestinal metabolic homeostasis

Sat, 11/03/2023 - 12:00
Phytomedicine. 2023 Mar 2;113:154737. doi: 10.1016/j.phymed.2023.154737. Online ahead of print.ABSTRACTBACKGROUND: Antibiotic-associated diarrhea (AAD) has had a significant increase in the last years, with limited available effective therapies. Shengjiang Xiexin Decoction (SXD), a classic traditional Chinese medicine formula for treating diarrhea, is a promising alternative for reducing the incidence of AAD.PURPOSE: This study aimed to explore the therapeutic effect of SXD on AAD and to investigate its potential therapeutic mechanism by integrated analysis of the gut microbiome and intestinal metabolic profile.METHODS: 16S rRNA sequencing analysis of the gut microbiota and untargeted-metabolomics analysis of feces were performed. The mechanism was further explored by fecal microbiota transplantation (FMT).RESULTS: SXD could effectively ameliorate AAD symptoms and restore intestinal barrier function. In addition, SXD could significantly improve the diversity of the gut microbiota and accelerate the recovery of the gut microbiota. At the genus level, SXD significantly increased the relative abundance of Bacteroides spp (p < 0.01) and decreased the relative abundance of Escherichia_Shigela spp (p < 0.001). Untargeted metabolomics showed that SXD significantly improved gut microbiota and host metabolic function, particularly bile acid metabolism and amino acid metabolism.CONCLUSION: This study demonstrated that SXD could extensively modulate the gut microbiota and intestinal metabolic homeostasis to treat AAD.PMID:36905867 | DOI:10.1016/j.phymed.2023.154737

Transcriptomic and metabolomic insights into the defense response to HFRs in Arabidopsis

Sat, 11/03/2023 - 12:00
Ecotoxicol Environ Saf. 2023 Mar 9;254:114736. doi: 10.1016/j.ecoenv.2023.114736. Online ahead of print.ABSTRACTTetrabromobisphenol A (TBBPA), Tetrachlorobisphenol A (TCBPA), Tetrabromobisphenol S (TBBPS) and their derivatives as the most widely used halogenated flame retardants (HFR), had been employed in the manufacturing industry to raise fire safety. HFRs have been shown to be developmentally toxic to animals and also affect plant growth. However, little was known about the molecular mechanism responded by when plants were treated with these compounds. In this study, when Arabidopsis was exposed to four HFRs (TBBPA, TCBPA, TBBPS-MDHP, TBBPS), the stress of these compounds had different inhibitory effects on seed germination and plant growth. Transcriptome and metabolome analysis showed that all four HFRs could influence the expression of transmembrane transporters to affect ion transport, Phenylpropanoid biosynthesis, Plant-pathogen interaction, MAPK signalling pathway and other pathways. In addition, the effects of different kinds of HFR on plants also have variant characteristics. It is very fascinating that Arabidopsis shows the response of biotic stress after exposure to these kinds of compounds, including the immune mechanism. Overall, the findings of the mechanism recovered by methods of transcriptome and metabolome analysis supplied a vital insight into the molecular perspective for Arabidopsis response to HFRs stress.PMID:36905847 | DOI:10.1016/j.ecoenv.2023.114736

Geographical region traceability of Poria cocos and correlation between environmental factors and biomarkers based on a metabolomic approach

Sat, 11/03/2023 - 12:00
Food Chem. 2023 Mar 6;417:135817. doi: 10.1016/j.foodchem.2023.135817. Online ahead of print.ABSTRACTThe edible values of P. cocos from different origins vary significantly, therefore, it is important to investigate the traceability of geographical regions and identify the geographical biomarkers of P. cocos. The metabolites of P. cocos of the different geographical origins were assessed using liquid chromatography tandem-mass spectrometry, principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). The OPLS-DA could clearly discriminate the metabolites of P. cocos from the three cultivation regions (YN, Yunnan; AH, Anhui; JZ, Hunan). Finally, three carbohydrates, four amino acids, and four triterpenoids were selected as biomarkers for P. cocos origin tracing. Correlation matrix analysis revealed that the contents of biomarkers were closely related to geographical origin. Altitude, temperature, and soil fertility were the main factors responsible for the differences in biomarker profiles in P. cocos. The metabolomics approach provides an effective strategy for tracing and identifying the biomarkers of P. cocos from different geographical origins.PMID:36905692 | DOI:10.1016/j.foodchem.2023.135817

Dietary, locomotory, and metabolic reactions of Abax parallelus (Coleoptera, Carabidae) to acute thiamethoxam intoxication

Sat, 11/03/2023 - 12:00
Ecotoxicology. 2023 Mar 11. doi: 10.1007/s10646-023-02638-7. Online ahead of print.ABSTRACTCarabids (Coleoptera: Carabidae) are abundant predators in ecosystems and serve as pest biocontrol in agroecosystems and forestry. Here we test the impact of thiamethoxam, among the most used neonicotinoids on the consumption rate, locomotion, metabolomics, and oxidative stress level measuring superoxide dismutase (SOD) activity in a predatory carabid, Abax parallelus (Duftschmid, 1812), after acute exposure in the laboratory trials, to get additional data that might link the use of pesticides and predation efficiency. Beetles were exposed to increasing concentrations of thiamethoxam by dipping method, and left to feed overnight prior to the assays. The results showed that individuals treated with higher concentrations of thiamethoxam (20 and 40 mg/L) consumed significantly less food per body weight and had a higher share of intoxicated and moribund individuals. The mass of consumed food per beetle body weight and observed locomotion did not differ significantly between control and groups treated with lower concentrations of thiamethoxam. There are significant differences in concentrations of some metabolites between treated and control individuals, primary in succinate and d-glucose, indicating a disruption in energy production. On the other hand, there is no statistically significant differences in SOD activity among the groups. To conclude, acute exposure to thiamethoxam can result in negative sub-lethal effects in predatory activity and energy budget, while the effects of long-term exposure to lower doses require further research, as well as field assessment on the predation efficiency after pesticide application.PMID:36905482 | DOI:10.1007/s10646-023-02638-7

Multi-omics studies in interpreting the evolving standard model for immune functions

Sat, 11/03/2023 - 12:00
Brief Funct Genomics. 2023 Mar 10:elad003. doi: 10.1093/bfgp/elad003. Online ahead of print.ABSTRACTA standard model that is able to generalize data on myriad involvement of the immune system in organismal physio-pathology and to provide a unified evolutionary teleology for immune functions in multicellular organisms remains elusive. A number of such 'general theories of immunity' have been proposed based on contemporaneously available data, starting with the usual description of self-nonself discrimination, followed by the 'danger model' and the more recent 'discontinuity theory.' More recent data deluge on involvement of immune mechanisms in a wide variety of clinical contexts, a number of which fail to get readily accommodated into the available teleologic standard models, makes deriving a standard model of immunity more challenging. But technological advances enabling multi-omics investigations into an ongoing immune response, covering genome, epigenome, coding and regulatory transcriptome, proteome, metabolome and tissue-resident microbiome, bring newer opportunities for developing a more integrative insight into immunocellular mechanisms within different clinical contexts. The new ability to map the heterogeneity of composition, trajectory and endpoints of immune responses, in both health and disease, also necessitates incorporation into the potential standard model of immune functions, which again can only be achieved through multi-omics probing of immune responses and integrated analyses of the multi-dimensional data.PMID:36905355 | DOI:10.1093/bfgp/elad003

Dietary Sources of Anthocyanins and Their Association with Metabolome Biomarkers and Cardiometabolic Risk Factors in an Observational Study

Sat, 11/03/2023 - 12:00
Nutrients. 2023 Feb 28;15(5):1208. doi: 10.3390/nu15051208.ABSTRACTAnthocyanins (ACNs) are (poly)phenols associated with reduced cardiometabolic risk. Associations between dietary intake, microbial metabolism, and cardiometabolic health benefits of ACNs have not been fully characterized. Our aims were to study the association between ACN intake, considering its dietary sources, and plasma metabolites, and to relate them with cardiometabolic risk factors in an observational study. A total of 1351 samples from 624 participants (55% female, mean age: 45 ± 12 years old) enrolled in the DCH-NG MAX study were studied using a targeted metabolomic analysis. Twenty-four-hour dietary recalls were used to collect dietary data at baseline, six, and twelve months. ACN content of foods was calculated using Phenol Explorer and foods were categorized into food groups. The median intake of total ACNs was 1.6mg/day. Using mixed graphical models, ACNs from different foods showed specific associations with plasma metabolome biomarkers. Combining these results with censored regression analysis, metabolites associated with ACNs intake were: salsolinol sulfate, 4-methylcatechol sulfate, linoleoyl carnitine, 3,4-dihydroxyphenylacetic acid, and one valerolactone. Salsolinol sulfate and 4-methylcatechol sulfate, both related to the intake of ACNs mainly from berries, were inversely associated with visceral adipose tissue. In conclusion, plasma metabolome biomarkers of dietary ACNs depended on the dietary source and some of them, such as salsolinol sulfate and 4-methylcatechol sulfate may link berry intake with cardiometabolic health benefits.PMID:36904207 | DOI:10.3390/nu15051208

Red Meat Intake, Indole-3-Acetate, and <em>Dorea longicatena</em> Together Affect Insulin Resistance after Gastric Bypass

Sat, 11/03/2023 - 12:00
Nutrients. 2023 Feb 27;15(5):1185. doi: 10.3390/nu15051185.ABSTRACTRoux-en-Y Gastric bypass (RYGB) promotes improvement in type 2 diabetes (T2D) shortly after surgery, with metabolic mechanisms yet to be elucidated. This study aimed to investigate the relationship between food intake, tryptophan metabolism, and gut microbiota on the glycemic control of obese T2D women after RYGB surgery. Twenty T2D women who underwent RYGB were evaluated before and three months after surgery. Food intake data were obtained by a seven-day food record and a food frequency questionnaire. Tryptophan metabolites were determined by untargeted metabolomic analysis, and the gut microbiota was determined by 16S rRNA sequencing. The glycemic outcomes were fasting blood glucose, HbA1C, HOMA-IR, and HOMA-beta. Linear regression models were applied to assess the associations between the changes in food intake, tryptophan metabolism, and gut microbiota on glycemic control after RYGB. All variables changed after RYGB (p < 0.05), except for tryptophan intake. Jointly, the variation in red meat intake, plasma indole-3-acetate, and Dorea longicatena was associated with postoperative HOMA-IR {R2 0.80, R2 adj 0.74; p < 0.01}. Red meat intake decreased three months after bariatric surgery while indole-3-acetate and Dorea longicatena increased in the same period. These combined variables were associated with better insulin resistance in T2D women after RYGB.PMID:36904185 | DOI:10.3390/nu15051185

Integrated Analysis of Gut Microbiome and Liver Metabolome to Evaluate the Effects of Fecal Microbiota Transplantation on Lipopolysaccharide/D-galactosamine-Induced Acute Liver Injury in Mice

Sat, 11/03/2023 - 12:00
Nutrients. 2023 Feb 24;15(5):1149. doi: 10.3390/nu15051149.ABSTRACTAcute liver failure (ALF) refers to the occurrence of massive hepatocyte necrosis in a short time, with multiple complications, including inflammatory response, hepatic encephalopathy, and multiple organ failure. Additionally, effective therapies for ALF are lacking. There exists a relationship between the human intestinal microbiota and liver, so intestinal microbiota modulation may be a strategy for therapy of hepatic diseases. In previous studies, fecal microbiota transplantation (FMT) from fit donors has been used to modulate intestinal microbiota widely. Here, we established a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-gal) induced ALF to explore the preventive and therapeutic effects of FMT, and its mechanism of action. We found that FMT decreased hepatic aminotransferase activity and serum total bilirubin levels, and decreased hepatic pro-inflammatory cytokines in LPS/D-gal challenged mice (p < 0.05). Moreover, FMT gavage ameliorated LPS/D-gal induced liver apoptosis and markedly reduced cleaved caspase-3 levels, and improved histopathological features of the liver. FMT gavage also restored LPS/D-gal-evoked gut microbiota dysbiosis by modifying the colonic microbial composition, improving the abundance of unclassified_o_Bacteroidales (p < 0.001), norank_f_Muribaculaceae (p < 0.001), and Prevotellaceae_UCG-001 (p < 0.001), while reducing that of Lactobacillus (p < 0.05) and unclassified_f_Lachnospiraceae (p < 0.05). Metabolomics analysis revealed that FMT significantly altered LPS/D-gal induced disordered liver metabolites. Pearson's correlation revealed strong correlations between microbiota composition and liver metabolites. Our findings suggest that FMT ameliorate ALF by modulating gut microbiota and liver metabolism, and can used as a potential preventive and therapeutic strategy for ALF.PMID:36904149 | DOI:10.3390/nu15051149

Prolonged Egg Supplement Advances Growing Child's Growth and Gut Microbiota

Sat, 11/03/2023 - 12:00
Nutrients. 2023 Feb 24;15(5):1143. doi: 10.3390/nu15051143.ABSTRACTProtein-energy malnutrition still impacts children's growth and development. We investigated the prolonged effects of egg supplementation on growth and microbiota in primary school children. For this study, 8-14-year-old students (51.5% F) in six rural schools in Thailand were randomly assigned into three groups: (1) whole egg (WE), consuming 10 additional eggs/week (n = 238) (n = 238); (2) protein substitute (PS), consuming yolk-free egg substitutes equivalent to 10 eggs/week (n = 200); and (3) control group (C, (n = 197)). The outcomes were measured at week 0, 14, and 35. At the baseline, 17% of the students were underweight, 18% were stunted, and 13% were wasted. At week 35, compared to the C group the weight and height difference increased significantly in the WE group (3.6 ± 23.5 kg, p < 0.001; 5.1 ± 23.2 cm, p < 0.001). No significant differences in weight or height were observed between the PS and C groups. Significant decreases in atherogenic lipoproteins were observed in the WE, but not in PS group. HDL-cholesterol tended to increase in the WE group (0.02 ± 0.59 mmol/L, ns). The bacterial diversity was similar among the groups. The relative abundance of Bifidobacterium increased by 1.28-fold in the WE group compared to the baseline and differential abundance analysis which indicated that Lachnospira increased and Varibaculum decreased significantly. In conclusion, prolonged whole egg supplementation is an effective intervention to improve growth, nutritional biomarkers, and gut microbiota with unaltered adverse effects on blood lipoproteins.PMID:36904143 | DOI:10.3390/nu15051143

Metabolomic Diversity of Human Milk Cells over the Course of Lactation-A Preliminary Study

Sat, 11/03/2023 - 12:00
Nutrients. 2023 Feb 22;15(5):1100. doi: 10.3390/nu15051100.ABSTRACTHuman milk (HM) is a complex biofluid containing a wide cell variety including epithelial cells and leukocytes. However, the cellular compositions and their phenotypic properties over the course of lactation are poorly understood. The aim of this preliminary study was to characterize the cellular metabolome of HM over the course of lactation. Cells were isolated via centrifugation and the cellular fraction was characterized via cytomorphology and immunocytochemical staining. Cell metabolites were extracted and analyzed using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QqTOF-MS) in the positive and negative electrospray ionization modes. Immunocytochemical analysis revealed a high variability of the number of detected cells with relative median abundances of 98% of glandular epithelial cells, 1% of leukocytes, and 1% of keratinocytes. Significant correlations between the milk postnatal age with percentage of epithelial cells and leukocytes, and with total cell count were observed. Results from the Hierarchical Cluster Analysis of immunocytochemical profiles were very similar to those observed in the analysis of the metabolomic profiles. In addition, metabolic pathway analysis showed alterations in seven metabolic pathways correlating with postnatal age. This work paves the way for future investigations on changes in the metabolomic fraction of the cellular compartment of HM.PMID:36904100 | DOI:10.3390/nu15051100

Metabolomic Analysis of Key Metabolites and Their Pathways Revealed the Response of Alfalfa (<em>Medicago sativa</em> L.) Root Exudates to <em>rac</em>-GR24 under Drought Stress

Sat, 11/03/2023 - 12:00
Plants (Basel). 2023 Mar 3;12(5):1163. doi: 10.3390/plants12051163.ABSTRACTThe rac-GR24, an artificial analog of strigolactone, is known for its roles in inhibiting branches, and previous studies have reported that it has a certain mechanism to relieve abiotic stress, but the underlying metabolic mechanisms of mitigation for drought-induced remain unclear. Therefore, the objectives of this study were to identify associated metabolic pathways that are regulated by rac-GR24 in alfalfa (Medicago sativa L.) and to determine the metabolic mechanisms of rac-GR24 that are involved in drought-induced root exudate. The alfalfa seedling WL-712 was treated with 5% PEG to simulate drought, and rac-GR24 at a concentration of 0.1 µM was sprayed. After three days of treatment, root secretions within 24 h were collected. Osmotic adjustment substances and antioxidant enzyme activities were measured as physiological indicators, while LS/MS was performed to identify metabolites regulated by rac-GR24 of root exudate under drought. The results demonstrated that rac-GR24 treatment could alleviate the negative effects from drought-induced on alfalfa root, as manifested by increased osmotic adjustment substance content, cell membrane stability, and antioxidant enzyme activities. Among the 14 differential metabolites, five metabolites were uniquely downregulated in plants in rac-GR24 treatment. In addition, rac-GR24 could relieve drought-induced adverse effects on alfalfa through metabolic reprogramming in the pathways of the TCA cycle, pentose phosphate, tyrosine metabolism, and the purine pathway. This study indicated that rac-GR24 could improve the drought resistance of alfalfa by influencing the components of root exudates.PMID:36904026 | DOI:10.3390/plants12051163

Proteome Analysis of <em>Nicotiana tabacum</em> Cells following Isonitrosoacetophenone Treatment Reveals Defence-Related Responses Associated with Priming

Sat, 11/03/2023 - 12:00
Plants (Basel). 2023 Mar 2;12(5):1137. doi: 10.3390/plants12051137.ABSTRACTProteins play an essential regulatory role in the innate immune response of host plants following elicitation by either biotic or abiotic stresses. Isonitrosoacetophenone (INAP), an unusual oxime-containing stress metabolite, has been investigated as a chemical inducer of plant defence responses. Both transcriptomic and metabolomic studies of various INAP-treated plant systems have provided substantial insight into this compound's defence-inducing and priming capabilities. To complement previous 'omics' work in this regard, a proteomic approach of time-dependent responses to INAP was followed. As such, Nicotiana tabacum (N. tabacum) cell suspensions were induced with INAP and changes monitored over a 24-h period. Protein isolation and proteome analysis at 0, 8, 16 and 24 h post-treatment were performed using two-dimensional electrophoresis followed by the gel-free eight-plex isobaric tags for relative and absolute quantitation (iTRAQ) based on liquid chromatography and mass spectrometry. Of the identified differentially abundant proteins, 125 were determined to be significant and further investigated. INAP treatment elicited changes to the proteome that affected proteins from a wide range of functional categories: defence, biosynthesis, transport, DNA and transcription, metabolism and energy, translation and signalling and response regulation. The possible roles of the differentially synthesised proteins in these functional classes are discussed. Results indicate up-regulated defence-related activity within the investigated time period, further highlighting a role for proteomic changes in priming as induced by INAP treatment.PMID:36903995 | DOI:10.3390/plants12051137

Moonlight Is Perceived as a Signal Promoting Genome Reorganization, Changes in Protein and Metabolite Profiles and Plant Growth

Sat, 11/03/2023 - 12:00
Plants (Basel). 2023 Mar 2;12(5):1121. doi: 10.3390/plants12051121.ABSTRACTRhythmic exposure to moonlight has been shown to affect animal behavior, but its effects on plants, often observed in lunar agriculture, have been doubted and often regarded as myth. Consequently, lunar farming practices are not well scientifically supported, and the influence of this conspicuous environmental factor, the moon, on plant cell biology has hardly been investigated. We studied the effect of full moonlight (FML) on plant cell biology and examined changes in genome organization, protein and primary metabolite profiles in tobacco and mustard plants and the effect of FML on the post-germination growth of mustard seedlings. Exposure to FML was accompanied by a significant increase in nuclear size, changes in DNA methylation and cleavage of the histone H3 C-terminal region. Primary metabolites associated with stress were significantly increased along with the expression of stress-associated proteins and the photoreceptors phytochrome B and phototropin 2; new moon experiments disproved the light pollution effect. Exposure of mustard seedlings to FML enhanced growth. Thus, our data show that despite the low-intensity light emitted by the moon, it is an important environmental factor perceived by plants as a signal, leading to alteration in cellular activities and enhancement of plant growth.PMID:36903981 | DOI:10.3390/plants12051121

Effects of Coumarin on Rhizosphere Microbiome and Metabolome of <em>Lolium multiflorum</em>

Sat, 11/03/2023 - 12:00
Plants (Basel). 2023 Mar 1;12(5):1096. doi: 10.3390/plants12051096.ABSTRACTRhizosphere microorganisms can help plants absorb nutrients, coordinate their growth, and improve their environmental adaptability. Coumarin can act as a signaling molecule that regulates the interaction between commensals, pathogens, and plants. In this study, we elucidate the effect of coumarin on plant root microorganisms. To provide a theoretical basis for the development of coumarin-derived compounds as biological pesticides, we determined the effect of coumarin on the root secondary metabolism and rhizosphere microbial community of annual ryegrass (Lolium multiflorum Lam.). We observed that a 200 mg/kg coumarin treatment had a negligible effect on the rhizosphere soil bacterial species of the annual ryegrass rhizosphere, though it exhibited a significant effect on the abundance of bacteria in the rhizospheric microbial community. Under coumarin-induced allelopathic stress, annual ryegrass can stimulate the colonization of beneficial flora in the root rhizosphere; however, certain pathogenic bacteria, such as Aquicella species, also multiply in large numbers in such conditions, which may be one of the main reasons for a sharp decline in the annual ryegrass biomass production. Further, metabolomics analysis revealed that the 200 mg/kg coumarin treatment triggered the accumulation of a total of 351 metabolites, of which 284 were found to be significantly upregulated, while 67 metabolites were significantly downregulated in the T200 group (treated with 200 mg/kg coumarin) compared to the CK group (control group) (p < 0.05). Further, the differentially expressed metabolites were primarily associated with 20 metabolic pathways, including phenylpropanoid biosynthesis, flavonoid biosynthesis, glutathione metabolism, etc. We found significant alterations in the phenylpropanoid biosynthesis and purine metabolism pathways (p < 0.05). In addition, there were significant differences between the rhizosphere soil bacterial community and root metabolites. Furthermore, changes in the bacterial abundance disrupted the balance of the rhizosphere micro-ecosystem and indirectly regulated the level of root metabolites. The current study paves the way towards comprehensively understanding the specific relationship between the root metabolite levels and the abundance of the rhizosphere microbial community.PMID:36903956 | DOI:10.3390/plants12051096

The Metabolites and Mechanism Analysis of Genistin against Hyperlipidemia via the UHPLC-Q-Exactive Orbitrap Mass Spectrometer and Metabolomics

Sat, 11/03/2023 - 12:00
Molecules. 2023 Feb 28;28(5):2242. doi: 10.3390/molecules28052242.ABSTRACTGenistin, an isoflavone, has been reported to have multiple activities. However, its improvement of hyperlipidemia is still unclear, and the same is true with regard to its mechanism. In this study, a high-fat diet (HFD) was used to induce a hyperlipidemic rat model. The metabolites of genistin in normal and hyperlipidemic rats were first identified to cause metabolic differences with Ultra-High-Performance Liquid Chromatography Quadrupole Exactive Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap MS). The relevant factors were determined via ELISA, and the pathological changes of liver tissue were examined via H&E staining and Oil red O staining, which evaluated the functions of genistin. The related mechanism was elucidated through metabolomics and Spearman correlation analysis. The results showed that 13 metabolites of genistin were identified in plasma from normal and hyperlipidemic rats. Of those metabolites, seven were found in normal rat, and three existed in two models, with those metabolites being involved in the reactions of decarbonylation, arabinosylation, hydroxylation, and methylation. Three metabolites, including the product of dehydroxymethylation, decarbonylation, and carbonyl hydrogenation, were identified in hyperlipidemic rats for the first time. Accordingly, the pharmacodynamic results first revealed that genistin could significantly reduce the level of lipid factors (p < 0.05), inhibited lipid accumulation in the liver, and reversed the liver function abnormalities caused by lipid peroxidation. For metabolomics results, HFD could significantly alter the levels of 15 endogenous metabolites, and genistin could reverse them. Creatine might be a beneficial biomarker for the activity of genistin against hyperlipidemia, as revealed via multivariate correlation analysis. These results, which have not been reported in the previous literature, may provide the foundation for genistin as a new lipid-lowering agent.PMID:36903488 | DOI:10.3390/molecules28052242

Untargeted Metabolomics Combined with Sensory Analysis to Evaluate the Chemical Changes in Coppa Piacentina PDO during Different Ripening Times

Sat, 11/03/2023 - 12:00
Molecules. 2023 Feb 27;28(5):2223. doi: 10.3390/molecules28052223.ABSTRACTRipening time is known to drive the chemical and sensory profiles of dry meat products, thus potentially affecting the final quality of the product. Starting from these background conditions, the aim of this work was to shed light, for the first time, on the chemical modifications of a typical Italian PDO meat product-namely, Coppa Piacentina-during ripening, to find correlations between its sensory quality and the biomarker compounds related to the progress of ripening. The ripening time (from 60 to 240 days) was found to deeply modify the chemical composition of this typical meat product, providing potential biomarkers of both oxidative reactions and sensory attributes. The chemical analyses revealed that there is typically a significant decrease in the moisture content during ripening, likely due to increased dehydration. In addition, the fatty acid profile showed that the distribution of polyunsaturated fatty acids significantly (p < 0.05) decreased during ripening, because of their high susceptibility to oxidation and conversion to intermediate and secondary molecules. An untargeted metabolomics approach, coupled with unsupervised and supervised multivariate statistics, highlighted a significant impact (prediction scores > 1) of lipid oxidation during ripening time, with some metabolites (such as γ -glutamyl-peptides, hydroperoxy-fatty acids, and glutathione) being particularly discriminant in predicting the changes observed. The discriminant metabolites were coherent with the progressive increase of peroxide values determined during the entire ripening period. Finally, the sensory analysis outlined that the highest degree of ripening provided greater color intensity of the lean part, slice firmness, and chewing consistency, with glutathione and γ-glutamyl-glutamic acid establishing the highest number of significant correlations with the sensory attributes evaluated. Taken together, this work highlights the importance and validity of untargeted metabolomics coupled with sensory analysis to investigate the comprehensive chemical and sensory changes to dry meat during ripening.PMID:36903465 | DOI:10.3390/molecules28052223

Discovering Hair Biomarkers of Alzheimer's Disease Using High Resolution Mass Spectrometry-Based Untargeted Metabolomics

Sat, 11/03/2023 - 12:00
Molecules. 2023 Feb 25;28(5):2166. doi: 10.3390/molecules28052166.ABSTRACTHair may be a potential biospecimen to discover biomarkers for Alzheimer's disease (AD) since it reflects the integral metabolic profiles of body burden over several months. Here, we described the AD biomarker discovery in the hair using a high-resolution mass spectrometry (HRMS)-based untargeted metabolomics approach. A total of 24 patients with AD and 24 age- and sex-matched cognitively healthy controls were recruited. The hair samples were collected 0.1-cm away from the scalp and further cut into 3-cm segments. Hair metabolites were extracted by ultrasonication with methanol/phosphate-buffered saline 50/50 (v/v) for 4 h. A total of 25 discriminatory chemicals in hair between the patients with AD and controls were discovered and identified. The AUC value achieved 0.85 (95% CI: 0.72~0.97) in patients with very mild AD compared to healthy controls using a composite panel of the 9 biomarker candidates, indicating high potential for the initiation or promotion phase of AD dementia in the early stage. A metabolic panel combined with the nine metabolites may be used as biomarkers for the early detection of AD. The hair metabolome can be used to reveal metabolic perturbations for biomarker discovery. Investigating perturbations of the metabolites will offer insight into the pathogenesis of AD.PMID:36903413 | DOI:10.3390/molecules28052166

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