PubMed

Curr Opin Biotechnol. 2023 Jan 6;79:102876. doi: 10.1016/j.copbio.2022.102876. Online ahead of print.ABSTRACTClustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) gene editing has become a powerful tool in genome manipulation for crop improvement. Advances in omics technologies, including genomics, transcriptomics, and metabolomics, allow the identification of causal genes that can be used to improve crops. However, the functional validation of these genetic components remains a challenge due to the lack of efficient protocols for crop engineering. Hairy roots gene editing using CRISPR/Cas, coupled with omics analyses, provide a platform for rapid, precise, and cost-effective functional analysis of genes. Here, we describe common requirements for efficient crop genome editing, focused on the transformation of recalcitrant legumes, and highlight the great opportunities that gene editing in hairy roots offers for future crop improvement.PMID:36621223 | DOI:10.1016/j.copbio.2022.102876

Front Psychiatry. 2022 Dec 21;13:998709. doi: 10.3389/fpsyt.2022.998709. eCollection 2022.ABSTRACTINTRODUCTION: Schizophrenia (SZ) is a severe chronic mental disorder with increased risk of hepatitis B virus (HBV) infection, which is incurable currently and induces various negative emotions and psychological pressures in patients to exacerbate mental disorders. To facilitate the therapeutic design for SZ patients complicated with HBV infection (SZ + HBV), it is helpful to first elucidate the metabolic perturbations in SZ + HBV patients.METHODS: In this study, metabolic profiles of the serum samples from four groups of participants comprising healthy controls (HC, n = 72), HBV infection (n = 52), SZ patients (n = 37), and SZ + HBV (n = 41) patients were investigated using a high-resolution 1H NMR-based metabolomics approach.RESULTS AND DISCUSSION: Distinguishable metabolic profiles were found in the four groups. In comparison with HC, HBV infection induced increased levels of citrate and succinate to perturbate the tricarboxylic acid cycle and succinate-related pathways. Similar to SZ cases, SZ + HBV patients exhibited decreased glucose but increased citrate, pyruvate, and lactate, suggesting the occurrence of disturbance in glucose metabolism. Moreover, in comparison with HC, several serum amino acid levels in SZ + HBV patients were significantly altered. Our findings suggest that Warburg effect, energy metabolism disorders, neurotransmitter metabolism abnormalities, mitochondrial dysfunction and several disturbed pathways in relation to tyrosine and choline appear to play specific and central roles in the pathophysiology of SZ + HBV. Apart from replicating metabolic alterations induced by SZ and HBV separately (e.g., in energy metabolism and Warburg effect), the specific metabolic abnormalities in the SZ + HBV group (e.g., several tyrosine- and choline-related pathways) highlighted the existence of a synergistic action between SZ and HBV pathologies. Current study revealed the metabolic alterations specific to the interaction between SZ and HBV pathologies, and may open important perspectives for designing precise therapies for SZ + HBV patients beyond the simple combination of two individual treatments.PMID:36620683 | PMC:PMC9810819 | DOI:10.3389/fpsyt.2022.998709

Front Oncol. 2022 Dec 22;12:1069635. doi: 10.3389/fonc.2022.1069635. eCollection 2022.ABSTRACTUsing circulating molecular biomarkers to screen for cancer and other debilitating disorders in a high-throughput and low-cost fashion is becoming increasingly attractive in medicine. One major limitation of investigating protein biomarkers in body fluids is that only one-fourth of the entire proteome can be routinely detected in these fluids. In contrast, Human Leukocyte Antigen (HLA) presents peptides from the entire proteome on the cell surface. While peptide-HLA complexes are predominantly membrane-bound, a fraction of HLA molecules is released into body fluids which is referred to as soluble HLAs (sHLAs). As such peptides bound by sHLA molecules represent the entire proteome of their cells/tissues of origin and more importantly, recent advances in mass spectrometry-based technologies have allowed for accurate determination of these peptides. In this perspective, we discuss the current understanding of sHLA-peptide complexes in the context of cancer, and their potential as a novel, relatively untapped repertoire for cancer biomarkers. We also review the currently available tools to detect and quantify these circulating biomarkers, and we discuss the challenges and future perspectives of implementing sHLA biomarkers in a clinical setting.PMID:36620582 | PMC:PMC9815702 | DOI:10.3389/fonc.2022.1069635

Front Physiol. 2022 Dec 23;13:1072893. doi: 10.3389/fphys.2022.1072893. eCollection 2022.ABSTRACTApriona swainsoni is a vital forest pest prevalent in China. The larvae of A. swainsoni live solely in the branches of trees and rely entirely on the xylem for nutrition. However, there is still a lack of in-depth research on the gut microbiota's use of almost nitrogen-free wood components to provide bio-organic macromolecular components needed for their growth. Thus, in this study, the metagenome, metaproteome, and metabolome of the A. swainsoni larvae in four gut segments (foregut; midgut; anterior hindgut; posterior hindgut) were analyzed by the multi-omics combined technology, to explore the metabolic utilization mechanism of the corresponding gut microbiota of A. swainsoni. Firstly, we found that the metagenome of different gut segments was not significantly different in general, but there were different combinations of dominant bacteria and genes in different gut segments, and the metaproteome and metabolome of four gut segments were significantly different in general. Secondly, the multi-omics results showed that there were significant gradient differences in the contents of cellulose and hemicellulose in different segments of A. swainsoni, and the expression of corresponding metabolic proteins was the highest in the midgut, suggesting the metabolic characteristics of these lignocellulose components in A. swainsoni gut segments. Finally, we found that the C/N ratio of woody food was significantly lower than that of frass, and metagenomic results showed that nitrogen fixation genes mainly existed in the foregut and two hindgut segments. The expression of the key nitrogen fixing gene nifH occurred in two hindgut parts, indicating the feature of nitrogen fixation of A. swainsoni. In conclusion, our results provide direct evidence that the larvae of A. swainsoni can adapt to the relatively harsh niche conditions through the highly organized gut microbiome in four gut segments, and may play a major role in their growth.PMID:36620205 | PMC:PMC9816477 | DOI:10.3389/fphys.2022.1072893

Front Microbiol. 2022 Dec 22;13:1085113. doi: 10.3389/fmicb.2022.1085113. eCollection 2022.ABSTRACTEngineered nanomaterials can provide eco-friendly alternatives for crop disease management. Chitosan based nanoparticles has shown beneficial applications in sustainable agricultural practices and effective healthcare. Previously we demonstrated that Thymol loaded chitosan nanoparticles (TCNPs) showed bactericidal activity against Xanthomonas campestris pv campestris (Xcc), a bacterium that causes black rot disease in brassica crops. Despite the progress in assessing the antibacterial action of TCNPs, the knowledge about the molecular response of Xcc when exposed to TCNPs is yet to be explored. In the present study, we combined physiological, spectroscopic and untargeted metabolomics studies to investigate the response mechanisms in Xcc induced by TCNPs. Cell proliferation and membrane potential assays of Xcc cells exposed to sub-lethal concentration of TCNPs showed that TCNPs affects the cell proliferation rate and damages the cell membrane altering the membrane potential. FTIR spectroscopy in conjunction with untargeted metabolite profiling using mass spectrometry of TCNPs treated Xcc cells revealed alterations in amino acids, lipids, nucleotides, fatty acids and antioxidant metabolites. Mass spectroscopy analysis revealed a 10-25% increase in nucleic acid, fatty acids and antioxidant metabolites and a 20% increase in lipid metabolites while a decrease of 10-20% in amino acids and carbohydrates was seen in in TCNP treated Xcc cells. Overall, our results demonstrate that the major metabolic perturbations induced by TCNPs in Xcc are associated with membrane damage and oxidative stress, thus providing information on the mechanism of TCNPs mediated cytotoxicity. This will aid towards the development of nano- based agrochemicals as an alternative to chemical pesticides in future.PMID:36620059 | PMC:PMC9815552 | DOI:10.3389/fmicb.2022.1085113

Front Microbiol. 2022 Dec 21;13:1046912. doi: 10.3389/fmicb.2022.1046912. eCollection 2022.ABSTRACTINTRODUCTION: High intake of dietary fiber is associated with lower incidence of cardiovascular diseases. Dietary fiber, functions as a prebiotic, has a significant impact on intestinal bacteria composition and diversity. The intestinal flora and metabolites generated by fermentation of dietary fiber not only affect the health of intestine but also play a role in many extra-intestinal diseases, such as obesity, diabetes and atherosclerosis. However, the role and the mechanism by which a high fiber diet contributes to the development of myocardial infarction is still unclear.METHODS AND RESULTS: Here we used an in vivo mouse model to investigate whether dietary fiber intake could protect against myocardial infarction. Our study demonstrated high fiber diet significantly improved cardiac function, reduced infarct size and prevented adverse remodeling following myocardial infarction. The protective effects of high fiber diet had a strong relation with its attenuation of inflammation. Moreover, we observed that high fiber diet could modulate the composition of intestinal flora and differentially impacted metabolites production, including the biosynthesis of bile acids and linoleic acid metabolism.CONCLUSION: Overall, the findings of this study provided mechanistic insights into the curative effect of dietary fiber on myocardial infarction with a specific emphasis on the potential role of microbiota-metabolism-immunity interactions.PMID:36620030 | PMC:PMC9810810 | DOI:10.3389/fmicb.2022.1046912

Front Microbiol. 2022 Dec 22;13:1042944. doi: 10.3389/fmicb.2022.1042944. eCollection 2022.ABSTRACTINTRODUCTION: Microbial communities in the plant rhizosphere are critical for nutrient cycling and ecosystem stability. However, how root exudates and soil physicochemical characteristics affect microbial community composition in Populus rhizosphere is not well understood.METHODS: This study measured soil physiochemistry properties and root exudates in a representative forest consists of four Populus species. The composition of rhizosphere bacterial and fungal communities was determined by metabolomics and high-throughput sequencing.RESULTS: Luvangetin, salicylic acid, gentisic acid, oleuropein, strigol, chrysin, and linoleic acid were the differential root exudates extracted in the rhizosphere of four Populus species, which explained 48.40, 82.80, 48.73, and 59.64% of the variance for the dominant and key bacterial or fungal communities, respectively. Data showed that differential root exudates were the main drivers of the changes in the rhizosphere microbial communities. Nitrosospira, Microvirga, Trichoderma, Cortinarius, and Beauveria were the keystone taxa in the rhizosphere microbial communities, and are thus important for maintaining a stable Populus microbial rhizosphere. The differential root exudates had strong impact on key bacteria than dominant bacteria, key fungi, and dominant fungi. Moreover, strigol had positively effects with bacteria, whereas phenolic compounds and chrysin were negatively correlated with rhizosphere microorganisms. The assembly process of the community structure (keystone taxa and bacterial dominant taxa) was mostly determined by stochastic processes.DISCUSSION: This study showed the association of rhizosphere microorganisms (dominant and keystone taxa) with differential root exudates in the rhizosphere of Populus plants, and revealed the assembly process of the dominant and keystone taxa. It provides a theoretical basis for the identification and utilization of beneficial microorganisms in Populus rhizosphere.PMID:36619999 | PMC:PMC9812961 | DOI:10.3389/fmicb.2022.1042944

Front Vet Sci. 2022 Dec 22;9:1027967. doi: 10.3389/fvets.2022.1027967. eCollection 2022.ABSTRACTWith diversification of yak breeding, it is important to understand the effects of feed type on the rumen, especially microbiota and metabolites. Due to the unique characteristics of yak, research on rumen microbes and metabolites is limited. In this study, the effects of two diet types on rumen eukaryotic microflora and metabolites were evaluated using the Illumina MiSeq platform and liquid chromatography-mass spectrometry (LC-MS). All identified protozoa belonged to Trichostomatia. At the genus level, the relative abundance of Metadinium and Eudiplodinium were significantly (p < 0.05) higher in the roughage group than that of concentrate group, while the concentrate group harbored more Isotricha. Ascomycota, Basidiomycota, and Neocallimastigomycota were the main fungal phyla, and the Wallemia, Chordomyces, Chrysosporium, Cladosporium, Scopulariopsis, and Acremonium genera were significantly (p < 0.05) more abundant in the roughage group than the concentrate group, while the concentrate group harbored more Aspergillus, Neocallimastix, Thermoascus, and Cystofilobasidium (p < 0.05). Metabolomics analysis showed that feed type significantly affected the metabolites of rumen protein digestion and absorption (L-proline, L-phenylalanine, L-tryosine, L-leucine, L-tryptophan, and β-alanine), purine metabolism (hypoxanthine, xanthine, guanine, guanosine, adenosine, and adenine), and other metabolic pathway. Correlation analysis revealed extensive associations between differential microorganisms and important metabolites. The results provide a basis for comprehensively understanding the effects of feed types on rumen microorganisms and metabolites of yaks. The findings also provide a reference and new directions for future research.PMID:36619966 | PMC:PMC9815454 | DOI:10.3389/fvets.2022.1027967

Front Cell Infect Microbiol. 2022 Dec 22;12:999627. doi: 10.3389/fcimb.2022.999627. eCollection 2022.ABSTRACTIntracerebral hemorrhage (ICH) is the most devastating subtype of stroke, but effective prevention and treatment strategies are lacking. Recently, gut microbiome and its metabolitesis are considered to be an influencing factor of stroke. However, little is known about the effects of the gut microbiome on ICH and host metabolic activity. Therefore, we used 16S sequencing, macrogenomics sequencing and untargeted metabolomics to explore the differences in gut microbial-metabolome interactions between patients with intracerebral hemorrhage and healthy control populations. We found a significant decrease in the phylum of Firmicutes and a significant increase of Bacteroidetes in ICH patients. At the genus level, Streptococcus, Bifidobacterium, Akkermansia, and Lactobacillus were more abundant in ICH patients. Macrogenomic analysis revealed active glycosaminoglycan degradation, heme synthesis, galactose degradation, lipopolysaccharide core region synthesis, and beta-Lactam resistance in ICH patients. Serum untargeted metabolomic analysis combined with ROC curves showed that octanoylcarnitine, decanoylcarnitine, dodecanoylcarnitine, glyceric acid, pyruvic acid, aspartic acid, methylcysteine, pyroglutamic acid, 9E-tetradecenoic acid, N-Acetylneuraminic acid, and aconitic acid were the best markers for the diagnosis of ICH. Correlation analysis showed that microbiome enriched in the gut of ICH patients were significantly correlated with serum metabolites, revealing a close correlation between the gut microbiome of ICH patients and the host metabolome, and significant differences from the healthy population. microbiota-host co-metabolites including pyruvic acid and 9E-tetradecenoic acid is associated with the the National Institutes of Health Stroke Scale (NIHSS) scores. In conclusion, microbiome-related metabolites in ICH patients was associated with the severity of ICH, the microbiota-host co-metabolites may be a potential may be potential therapeutic targets.PMID:36619742 | PMC:PMC9813413 | DOI:10.3389/fcimb.2022.999627

Front Endocrinol (Lausanne). 2022 Dec 22;13:1037289. doi: 10.3389/fendo.2022.1037289. eCollection 2022.ABSTRACTINTRODUCTION: Type 1 diabetes (T1D) is a chronic condition associated with multiple complications that substantially affect both the quality of life and the life-span of children. Untargeted Metabolomics has provided new insights into disease pathogenesis and risk assessment.METHODS: In this study, we characterized the serum metabolic profiles of 76 children with T1D and 65 gender- and age- matched healthy controls using gas chromatography coupled with timeof-flight mass spectrometry. In parallel, we comprehensively evaluated the clinical phenome of T1D patients, including routine blood and urine tests, and concentrations of cytokines, hormones, proteins, and trace elements.RESULTS: A total of 70 differential metabolites covering 11 metabolic pathways associated with T1D were identified, which were mainly carbohydrates, indoles, unsaturated fatty acids, amino acids, and organic acids. Subgroup analysis revealed that the metabolic changes were consistent among pediatric patients at different ages or gender but were closely associated with the duration of the disease.DISCUSSION: Carbohydrate metabolism, unsaturated fatty acid biosynthesis, and gut microbial metabolism were identified as distinct metabolic features of pediatric T1D. These metabolic changes were also associated with T1D, which may provide important insights into the pathogenesis of the complications associated with diabetes.PMID:36619558 | PMC:PMC9813493 | DOI:10.3389/fendo.2022.1037289

Front Endocrinol (Lausanne). 2022 Dec 22;13:1046159. doi: 10.3389/fendo.2022.1046159. eCollection 2022.ABSTRACTBACKGROUND: Hashimoto's thyroiditis, an autoimmune thyroid disease, shows high morbidity worldwide, particularly in female. Patients with Hashimoto's thyroiditis have an increasing risk of hypothyroidism during the occurrence and progression of Hashimoto's thyroiditis. In recent years, metabolomics has been widely applied in autoimmune diseases, especially thyroid disorders. However, metabolites analysis in Hashimoto's thyroiditis is still absent.METHODS: A total of 92 samples were collected, including 35 cases in the control group, 30 cases in the Hashimoto's thyroiditis with euthyroidism group, and 27 cases in the Hashimoto's thyroiditis with subclinical hypothyroidism group. SPSS 25.0 for statistical analysis and ROC curve, SIMCA 14.0, Metaboanalysis for multifactor analysis, and Origin 2021 for correlation analysis.RESULTS: 21 metabolites were identified. 10 metabolites were obtained from control group versus HTE group, 8 serum metabolites were abnormal between control group and HTS group, 3 metabolites were derived from HTE group versus HTS. Kyoto Encyclopedia of Genes and Genomes Enrichment analysis showed that fatty acid degradation, Arginine, and proline metabolism have a significant impact on HTE, while lysine degradation, tyrosine metabolism play an important role HTS group, compared to control group. In the comparison between the HTE and HTS group, Valine, leucine, and isoleucine degradation and Valine, leucine, and isoleucine biosynthesis exists a key role. Correlation analysis shows clinical are not related to metabolites. ROC curve indicates SM, LPC, PC can efficiency in identification patients with HT in different clinical stage from healthy individuals.CONCLUSION: Serum metabolites were changed in HT. Phospholipids such as SM, LPC, PC influence the pathogenesis of Hashimoto's thyroiditis. Fatty acid degradation and lysine degradation pathways have an impact on different clinical stage of HT.PMID:36619550 | PMC:PMC9814722 | DOI:10.3389/fendo.2022.1046159

Int J Med Sci. 2023 Jan 1;20(1):142-150. doi: 10.7150/ijms.77206. eCollection 2023.ABSTRACTMetformin is the most often prescribed drug for people with type 2 diabetes (T2D). More than 120 million patients with T2D use metformin worldwide. However, monotherapy fails to achieve glycemic control in a third of the treated patients. Genetics contribute to some of the inter-individual variations in glycemic response to metformin. Numerous pharmacogenetic studies have demonstrated that variations in genes related to pharmacokinetics and pharmacodynamics of metformin's encoding transporters are mainly associated with metformin response. The goal of this review is to evaluate the current state of metformin pharmacogenetics and metabolomics research, discuss the clinical and scientific issues that need to be resolved in order to increase our knowledge of patient response variability to metformin, and how to improve patient outcomes. Metformin's hydrophilic nature and absorption as well as its action mechanism and effectiveness on T2D initiation are discussed. The impacts of variations associated with various genes are analysed to identify and evaluate the effect of genetic polymorphisms on the therapeutic activity of metformin. The metabolic pattern of T2D and metformin is also indicated. This is to emphasise that studies of pharmacogenetics and metabolomics could expand our knowledge of metformin response in T2D.PMID:36619226 | PMC:PMC9812811 | DOI:10.7150/ijms.77206

Front Mol Biosci. 2022 Dec 21;9:1042231. doi: 10.3389/fmolb.2022.1042231. eCollection 2022.ABSTRACTBackground: Assessing detailed metabolism in exercising persons minute-to-minute has not been possible. We developed a "drop-of-blood" platform to fulfill that need. Our study aimed not only to demonstrate the utility of our methodology, but also to give insights into unknown mechanisms and new directions. Methods: We developed a platform, based on gas chromatography and mass spectrometry, to assess metabolism from a blood-drop. We first observed a single volunteer who ran 13 km in 60 min. We particularly monitored relative perceived exertion (RPE). We observed that 2,3-bisphosphoglycerate peaked at RPE in this subject. We next expanded these findings to women and men volunteers who performed an RPE-based exercise protocol to RPE at Fi O 2 20.9% or Fi O 2 14.5% in random order. Results: At 6 km, our subject reached his maximum relative perceived exertion (RPE); however, he continued running, felt better, and finished his run. Lactate levels had stably increased by 2 km, ketoacids increased gradually until the run's end, while the hypoxia marker, 2,3 bisphosphoglycerate, peaked at maximum relative perceived exertion. In our normal volunteers, the changes in lactate, pyruvate, ß hydroxybutyrate and a hydroxybutyrate were not identical, but similar to our model proband runner. Conclusion: Glucose availability was not the limiting factor, as glucose availability increased towards exercise end in highly exerted subjects. Instead, the tricarboxylic acid→oxphos pathway, lactate clearance, and thus and the oxidative capacity appeared to be the defining elements in confronting maximal exertion. These ideas must be tested further in more definitive studies. Our preliminary work suggests that our single-drop methodology could be of great utility in studying exercise physiology.PMID:36619172 | PMC:PMC9822726 | DOI:10.3389/fmolb.2022.1042231

Front Mol Biosci. 2022 Dec 21;9:1084060. doi: 10.3389/fmolb.2022.1084060. eCollection 2022.ABSTRACTA reliable method for metabolite extraction is central to mass spectrometry-based metabolomics. However, existing methods are lengthy, mostly due to the step of scraping cells from cell culture vessels, which restricts metabolomics in broader application such as lower cell numbers and high-throughput studies. Here, we present a simplified metabolite extraction (SiMeEx) method, to efficiently and quickly extract metabolites from adherent mammalian cells. Our method excludes the cell scraping step and therefore allows for a more efficient extraction of polar metabolites in less than 30 min per 12-well plate. We demonstrate that SiMeEx achieves the same metabolite recovery as using a standard method containing a scraping step, in various immortalized and primary cells. Omitting cell scraping does not compromise the performance of non-targeted and targeted GC-MS analysis, but enables metabolome analysis of cell culture on smaller well sizes down to 96-well plates. Therefore, SiMeEx demonstrates advantages not only on time and resources, but also on the applicability in high-throughput studies.PMID:36619169 | PMC:PMC9812552 | DOI:10.3389/fmolb.2022.1084060

Front Mol Biosci. 2022 Dec 21;9:1074285. doi: 10.3389/fmolb.2022.1074285. eCollection 2022.ABSTRACTAtherosclerosis is a life-threatening disease associated with morbidity and mortality in patients with type 2 diabetes (T2D). This study aimed to characterize a salivary signature of atherosclerosis based on evaluation of carotid intima-media thickness (IMT) to develop a non-invasive predictive tool for diagnosis and disease follow-up. Metabolites in saliva and plasma samples collected at admission and after treatment from 25 T2D patients hospitalized for 2 weeks to undergo medical treatment for diabetes were comprehensively profiled using metabolomic profiling with gas chromatography-mass spectrometry. Orthogonal partial least squares analysis, used to explore the relationships of IMT with clinical markers and plasma and salivary metabolites, showed that the top predictors for IMT included salivary allantoin and 1,5-anhydroglucitol (1,5-AG) at both the baseline examination at admission and after treatment. Furthermore, though treatment induced alterations in salivary levels of allantoin and 1,5-AG, it did not modify the association between IMT and these metabolites (p interaction > 0.05), and models with these metabolites combined yielded satisfactory diagnostic accuracy for the high IMT group even after treatment (area under curve = 0.819). Collectively, this salivary metabolite combination may be useful for non-invasive identification of T2D patients with a higher atherosclerotic burden in clinical settings.PMID:36619162 | PMC:PMC9815705 | DOI:10.3389/fmolb.2022.1074285

Front Pharmacol. 2022 Dec 21;13:1076960. doi: 10.3389/fphar.2022.1076960. eCollection 2022.ABSTRACTIntroduction: Ginkgo biloba L. leaf extract (GBLE) has been reported to be effective for alleviating cognitive and memory impairment in Alzheimer's disease (AD). Nevertheless, the potential mechanism remains unclear. Herein, this study aimed to explore the neuroprotective effects of GBLE on AD and elaborate the underlying therapeutic mechanism. Methods: Donepezil, the most widely prescribed drug for AD, was used as a positive control. An integrated metabolomics and lipidomics approach was adopted to characterize plasma metabolic phenotype of APP/PS1 double transgenic mice and describe the metabolomic and lipidomic fingerprint changes after GBLE intervention. The Morris water maze test and immunohistochemistry were applied to evaluate the efficacy of GBLE. Results: As a result, administration of GBLE significantly improved the cognitive function and alleviated amyloid beta (Aβ) deposition in APP/PS1 mice, showing similar effects to donepezil. Significant alterations were observed in metabolic signatures of APP/PS1 mice compared with wild type (WT) mice by metabolomic analysis. A total of 60 markedly altered differential metabolites were identified, including 28 lipid and lipid-like molecules, 13 organic acids and derivatives, 11 organic nitrogen compounds, and 8 other compounds, indicative of significant changes in lipid metabolism of AD. Further lipidomic profiling showed that the differential expressed lipid metabolites between APP/PS1 and WT mice mainly consisted of phosphatidylcholines, lysophosphatidylcholines, triglycerides, and ceramides. Taking together all the data, the plasma metabolic signature of APP/PS1 mice was primarily characterized by disrupted sphingolipid metabolism, glycerophospholipid metabolism, glycerolipid metabolism, and amino acid metabolism. Most of the disordered metabolites were ameliorated after GBLE treatment, 19 metabolites and 24 lipids of which were significantly reversely regulated (adjusted-p<0.05), which were considered as potential therapeutic targets of GBLE on AD. The response of APP/PS1 mice to GBLE was similar to that of donepezil, which significantly reversed the levels of 23 disturbed metabolites and 30 lipids. Discussion: Our data suggested that lipid metabolism was dramatically perturbed in the plasma of APP/PS1 mice, and GBLE might exert its neuroprotective effects by restoring lipid metabolic balance. This work provided a basis for better understanding the potential pathogenesis of AD and shed new light on the therapeutic mechanism of GBLE in the treatment of AD.PMID:36618950 | PMC:PMC9810818 | DOI:10.3389/fphar.2022.1076960

Front Nutr. 2022 Dec 22;9:1062323. doi: 10.3389/fnut.2022.1062323. eCollection 2022.ABSTRACTFu brick tea (FBT) and its extracts have good lipid-lowering effects and have been used in the treatment of obesity in previous studies. Unfortunately, the therapeutic effect of FBT on non-alcoholic fatty liver disease (NAFLD) has not been thoroughly studied. In this study, we explored the mechanism by which FBT alleviates NAFLD from the perspective of the gut microbiota and liver metabolites. The results showed that FBT could reduce the body weight, liver weight and abdominal fat of NAFLD mice, and improve liver pathological morphology, liver lipid deposition, blood lipids and liver function. Moreover, FBT improved the diversity of the gut microbiota and changed the profile of liver metabolism in NAFLD mice. Further studies showed that FBT could ameliorate the cecum barrier, and regulate the effects of factors related to lipid synthesis in the cecum and liver of NAFLD mice. In conclusion, the present study confirmed that FBT can alleviate high fat induced NAFLD by regulating the homeostasis of the gut microbiota and liver metabolites.PMID:36618677 | PMC:PMC9815510 | DOI:10.3389/fnut.2022.1062323

Front Plant Sci. 2022 Dec 23;13:1069191. doi: 10.3389/fpls.2022.1069191. eCollection 2022.ABSTRACTPhosphorus (P) is an essential macronutrient element for plant growth, and deficiency of inorganic phosphate (Pi) limits plant growth and yield. Elephant grass (Pennisetum purpureum) is an important fodder crop cultivated widely in tropical and subtropical areas throughout the world. However, the mechanisms underlying efficient P use in elephant grass under Pi deficiency remain poorly understood. In this study, the physiological and molecular responses of elephant grass leaves and roots to Pi deficiency were investigated. The results showed that dry weight, total P concentration, and P content decreased in Pi-deprived plants, but that acid phosphatase activity and P utilization efficiency (PUE) were higher than in Pi-sufficient plants. Regarding Pi starvation-responsive (PSR) genes, transcriptomics showed that 59 unigenes involved in Pi acquisition and transport (especially 18 purple acid phosphatase and 27 phosphate transporter 1 unigenes) and 51 phospholipase unigenes involved in phospholipids degradation or Pi-free lipids biosynthesis, as well as 47 core unigenes involved in the synthesis of phenylpropanoids and flavonoids, were significantly up-regulated by Pi deprivation in leaves or roots. Furthermore, 43 unigenes related to Pi-independent- or inorganic pyrophosphate (PPi)-dependent bypass reactions were markedly up-regulated in Pi-deficient leaves, especially five UDP-glucose pyrophosphorylase and 15 phosphoenolpyruvate carboxylase unigenes. Consistent with PSR unigene expression changes, metabolomics revealed that Pi deficiency significantly increased metabolites of Pi-free lipids, phenylpropanoids, and flavonoids in leaves and roots, but decreased phospholipid metabolites. This study reveals the mechanisms underlying the responses to Pi starvation in elephant grass leaves and roots, which provides candidate unigenes involved in efficient P use and theoretical references for the development of P-efficient elephant grass varieties.PMID:36618667 | PMC:PMC9817030 | DOI:10.3389/fpls.2022.1069191

Front Plant Sci. 2022 Dec 22;13:1102044. doi: 10.3389/fpls.2022.1102044. eCollection 2022.ABSTRACTEpitranscriptome constitutes a gene expression checkpoint in all living organisms. Nitrogen is an essential element for plant growth and development that influences gene expression at different levels such as epigenome, transcriptome, proteome, and metabolome. Therefore, our hypothesis is that changes in the epitranscriptome may regulate nitrogen metabolism. In this study, epitranscriptomic modifications caused by ammonium nutrition were monitored in maritime pine roots using Oxford Nanopore Technology. Transcriptomic responses mainly affected transcripts involved in nitrogen and carbon metabolism, defense, hormone synthesis/signaling, and translation. Global detection of epitranscriptomic marks was performed to evaluate this posttranscriptional mechanism in un/treated seedlings. Increased N6-methyladenosine (m6A) deposition in the 3'-UTR was observed in response to ammonium, which seems to be correlated with poly(A) lengths and changes in the relative abundance of the corresponding proteins. The results showed that m6A deposition and its dynamics seem to be important regulators of translation under ammonium nutrition. These findings suggest that protein translation is finely regulated through epitranscriptomic marks likely by changes in mRNA poly(A) length, transcript abundance and ribosome protein composition. An integration of multiomics data suggests that the epitranscriptome modulates responses to nutritional, developmental and environmental changes through buffering, filtering, and focusing the final products of gene expression.PMID:36618661 | PMC:PMC9815506 | DOI:10.3389/fpls.2022.1102044

Front Plant Sci. 2022 Dec 22;13:1102215. doi: 10.3389/fpls.2022.1102215. eCollection 2022.ABSTRACTGreen microalgae can accumulate neutral lipids, as part of a general lipid remodeling mechanism under stress such as nitrogen starvation. Lobosphaera incisa is of special interest because of its unique TAG acyl chain composition, especially 20:4 (n-6) can reach up to 21% of dry weight after nitrogen starvation. In order to identify factors that may influence the accumulation of polyunsaturated fatty acids (PUFAs), we identified recently a linoleate 13-lipoxygenase (LiLOX). It shares highest identity with plastidic enzymes from vascular plants and is induced upon nitrogen starvation. Here, we confirmed the localization of LiLOX in the stroma of plastids via transient expression in epithelial onion cells. In order to further characterize this enzyme, we focused on the identification of the endogenous substrate of LiLOX. In this regard, an ex vivo enzymatic assay, coupled with non-targeted analysis via mass spectrometry allowed the identification of MGDG, DGDG and PC as three substrate candidates, later confirmed via in vitro assays. Further investigation revealed that LiLOX has preferences towards the lipid class MGDG, which seems in agreement with its localization in the galactolipid rich plastid. Altogether, this study shows the first characterization of plastidic LOX from green algae, showing preference for MGDGs. However, lipidomics analysis did neither reveal an endogenous LiLOX product nor the final end product of MGDG oxidation. Nevertheless, the latter is a key to understanding the role of this enzyme and since its expression is highest during the degradation of the plastidic membrane, it is tempting to assume its involvement in this process.PMID:36618660 | PMC:PMC9813749 | DOI:10.3389/fpls.2022.1102215