PubMed

J Proteomics. 2023 Feb 11:104837. doi: 10.1016/j.jprot.2023.104837. Online ahead of print.ABSTRACTStarting in approximately 2010, broiler breast meat myopathies, specifically woody breast meat, white striping, spaghetti meat, and gaping have increased in prevalence in the broiler meat industry. Omic methods have been used to elucidate compositional, genetic, and biochemical differences between myopathic and normal breast meat and have provided information on the factors that contribute to these myopathies. This review paper focuses on the genomic, transcriptomic, proteomic, metabolomic, and other omics research that has been conducted to unravel the molecular mechanisms involved in the development of these myopathies and their associated factors and potential causes. SIGNIFICANCE: This review manuscript summarizes poultry meat quality defects, also referred to as myopathies, that have been evaluated using omics methods. Genomics, transcriptomics, proteomics, metabolomics and other methodologies have been used to understand the genetic predisposition, the protein expression, and the biochemical pathways that are associated with the expression of woody breast meat, white striping, and other myopathies. This has allowed researchers and the industry to differentiate between chicken breast meat with and without myopathic muscle as well as the environmental and genetic conditions that contribute to differences in biochemical pathways and lead to the phenotypes associate with these different myopathies.PMID:36781045 | DOI:10.1016/j.jprot.2023.104837

Clin Chim Acta. 2023 Feb 11:117252. doi: 10.1016/j.cca.2023.117252. Online ahead of print.ABSTRACTBACKGROUND: Lack of comprehending key factors of schizophrenia relapse has impeded its effective treatment, indicating that the mechanism clarification and available intervention of schizophrenia relapse required further amelioration.METHOD: Based on the integration of LC-MS and 1H-NMR metabolomics, a weighted correlation network was established to screen pivotal factors of accelerating schizophrenia relapse. Then, the cluster most correlated with schizophrenia relapse was explored, and the biological function of cluster was investigated. Next, the key biomarker related to schizophrenia relapse was obtained through multiple algorithms. Moreover, the Lilikoi algorithm and correlation analysis were implemented to reveal the association between key biomarker and schizophrenia relapse.RESULT: Results showed that 458 different forms of metabolites were identified for structuring the weighted correlation network. The module-trait correlation indicated that the turquoise module was the most highly correlated with schizophrenia relapse. Further, network analysis revealed that, in turquoise module, cluster 1 composed of 139 metabolites (involved in lipid metabolism and energy metabolism) was the most important subnetwork relevant to schizophrenia relapse. Finally, phenylalanylphenylalanine was recommended as the key biomarker related to schizophrenia relapse. Moreover, the correlation analysis indicated that phenylalanylphenylalanine might affect the progression of schizophrenia by intervening in energy metabolism.CONCLUSION: In summary, critical factors of schizophrenia relapse have been revealed in our research, expounding the schizophrenia progression more systemically, which could shed some light on improving the intervention of schizophrenia relapse.PMID:36781041 | DOI:10.1016/j.cca.2023.117252

Environ Pollut. 2023 Feb 11:121275. doi: 10.1016/j.envpol.2023.121275. Online ahead of print.ABSTRACTThe ecological risk of heavy metal-contaminated soil is usually evaluated by its oxidative stress on terrestrial animals, which are vulnerable to the impact of individual differences of animals and environmental conditions. Oxidative potential (OP) is the potential of particles to induce the formation of reactive oxygen species (ROS). In this study, OP of the in situ contaminated soils collected from an industrial site (i.e., 64.5-7783 mg/kg of Cu, 54.9-397 mg/kg of Pb, 278-2085 mg/kg of Zn and 0.615-121 mg/kg of Cd) were measured as 38.0-60.1 pmol/min/mg, and the water extractable Cu, Pb, Zn, and Cd in soils have been proved to contribute 89%-98% to OP. Oxidative stress in earthworms (Eisenia fetida) caused by the industrial contaminated soils can be reflected by the biomarkers such as 8-hydroxy-2'-deoxyguanosine, metallothionein, and antioxidant enzymes, and a negative correlation presents between the comprehensive biomarker response index and the OP of soils (r = -0.979, p < 0.01). This is the first time to propose a dose-response relationship between OP and oxidative stress. Metabolomic analysis also verified that the regulation of four ROS-related metabolites (i.e., l-pipecolate, 1-methylhistidine, 5-methoxytryptamine, and xanthosine) in earthworms treated with contaminated soil were directly correlated with OP values. These results indicate that OP can be used as an indicator for ecological risk assessment of heavy metal-contaminated soil, which provides a fast, stable and easily testable chemical method.PMID:36780977 | DOI:10.1016/j.envpol.2023.121275

J Nutr. 2023 Feb 11:S0022-3166(23)11102-3. doi: 10.1016/j.tjnut.2023.02.013. Online ahead of print.ABSTRACTBACKGROUND: In pregnancy, it is deemed choline is an essential nutrient and carnitine needs are increased but amounts remain undefined.OBJECTIVE: We aimed to measure choline and total dietary protein and dairy protein intake from food and supplements across pregnancy and the response to intake by profiling choline and carnitine metabolites across pregnancy and in cord blood.METHODS: An exploratory analysis of choline and protein intake from 3-day diet records and measures of 36 serum choline and carnitine metabolites in early (14-17 weeks) and late (36-38 weeks) pregnancy was conducted in participants from the Be Healthy in Pregnancy randomized to high dairy protein+walking exercise or usual care. Metabolites were measured in fasted maternal and cord serum using multisegment injection-capillary electrophoresis-mass spectrometry. Mixed ANOVA adjusted for body mass index was performed for comparison of metabolites across pregnancy and between intervention and control.RESULTS: In 104 participants, the median (Q1,Q3) total choline intake was 347 (263,427) mg/d in early and 322 (270,437) mg/d in late pregnancy. Only ∼20% of participants achieved the recommended Adequate Intake (450 mg/d) and ∼10% consumed supplemental choline (8-200 mg/d). Serum free choline (μmol/L) was higher in late compared to early pregnancy (12.9 (11.4,15.1) vs 9.68 (8.25,10.61), p<0.001) but choline downstream metabolites were similar across pregnancy. Serum carnitine (10.3 (9.01,12.2) vs 15.9 (14.1,17.9) μmol/L, p<0.001) and acetylcarnitine (2.35 (1.92,2.68) vs 3.0 (2.56,3.59), p<0.001)) were significantly lower in late pregnancy. High cord:maternal serum metabolite ratios were found in most measured metabolites.CONCLUSION: Despite inadequate choline intake serum free choline was elevated in late pregnancy and enriched in cord blood compared to maternal serum. Serum carnitine declined in late pregnancy despite a high protein diet. The higher cord:maternal concentrations in choline and carnitine metabolites suggests active uptake in late pregnancy, reflecting the importance of these circulating metabolites in fetal development.CLINICAL TRIAL REGISTRY: NCT01689961 (https://clinicaltrials.gov/ct2/show/NCT01689961?cond=NCT01689961&rank=1) Registered on 21 September 2012.PMID:36780943 | DOI:10.1016/j.tjnut.2023.02.013

Food Chem. 2023 Feb 10;413:135656. doi: 10.1016/j.foodchem.2023.135656. Online ahead of print.ABSTRACTRecent studies emphasize the improved nutritional and functional status of fermented okara; however, little is known about the metabolite change during fermentation and how it alters metabolic pathways. A metabolomics approach based on untargeted LC-MS reveals metabolic changes in okara fermented by Bacillus subtilis DC-15. We identified 761 differential metabolites, with the highest abundances found in amino acids, dipeptides, fatty acids, small molecule sugars, and vitamins. Moreover, these identified metabolites were mapped to their respective biosynthesis pathways in order to gain a better understanding of the biochemical reactions triggered by fermentation. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, 485 metabolites were enriched to metabolism-related pathways. They include 37 carbohydrate metabolites, 79 amino acid metabolites, and 22 lipid metabolites. As a result of okara fermentation, we observed a gradual enrichment of metabolites and stabilization of the compounds.PMID:36780856 | DOI:10.1016/j.foodchem.2023.135656

Talanta. 2023 Feb 3;257:124324. doi: 10.1016/j.talanta.2023.124324. Online ahead of print.ABSTRACTThis review provides an overview of the online hyphenation of Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) with separation methods to date. The online coupling between separation techniques (gas and liquid chromatography, capillary electrophoresis) and FT-ICR MS essentially raises questions of compromise and is not look as straightforward as hyphenation with other analyzers (QTOF-MS for instance). FT-ICR MS requires time to reach its highest resolving power and accuracy in mass measurement capabilities whereas chromatographic and electrophoretic peaks are transient. In many applications, the strengths and the weaknesses of each technique are balanced by their hyphenation. Untargeted "Omics" (e.g. proteomics, metabolomics, petroleomics, …) is one of the main areas of application for FT-ICR MS hyphenated to online separation techniques because of the complexity of the sample. FT-ICR MS achieves the required high mass measurement accuracy to determine accurate molecular formulae and resolution for isobar distinction. Meanwhile separation techniques highlight isomers and reduce the ion suppression effects extending the dynamic range. Even if the implementation of FT-ICR MS hyphenated with online separation methods is a little trickier (the art of compromise), this review shows that it provides unparalleled results to the scientific community (the art of the possible), along with raising the issue of its future in the field with the relentless technological progress.PMID:36780779 | DOI:10.1016/j.talanta.2023.124324

Reprod Fertil Dev. 2023 Feb 14. doi: 10.1071/RD22210. Online ahead of print.ABSTRACTCONTEXT: The exact mechanisms regulating the initiation of porcine conceptus elongation are not known due to the complexity of the uterine environment.AIMS: To identify contributing factors for initiation of conceptus elongation in vitro, this study evaluated differential metabolite abundance within media following culture of blastocysts within unmodified alginate (ALG) or Arg-Gly-Asp (RGD)-modified alginate hydrogel culture systems.METHODS: Blastocysts were harvested from pregnant gilts, encapsulated within ALG or RGD or as non-encapsulated control blastocysts (CONT), and cultured. At the termination of 96h culture, media were separated into blastocyst media groups: non-encapsulated control blastocysts (CONT); ALG and RGD blastocysts with no morphological change (ALG- and RGD-); ALG and RGD blastocysts with morphological changes (ALG+ and RGD+) and evaluated for non-targeted metabolomic profiling by liquid chromatography (LC)-mass spectrometry (MS) techniques and gas chromatography-(GC-MS).KEY RESULTS: Analysis of variance identified 280 (LC-MS) and 1 (GC-MS) compounds that differed (P<0.05), of which 134 (LC-MS) and 1 (GC-MS) were annotated. Metabolites abundance between ALG+ vs ALG-, RGD+ vs RGD-, and RGD+ vs ALG+ were further investigated to identify potential differences in metabolic processes during the initiation of elongation.CONCLUSIONS: This study identified changes in phospholipid, glycosphingolipid, lipid signalling, and amino acid metabolic processes as potential RGD-independent mechanisms of elongation and identified changes in lysophosphatidylcholine and sphingolipid secretions during RGD-mediated elongation.IMPLICATIONS: These results illustrate changes in phospholipid and sphingolipid metabolic processes and secretions may act as mediators of the RGD-integrin adhesion that promotes porcine conceptus elongation.PMID:36780705 | DOI:10.1071/RD22210

Neurogastroenterol Motil. 2023 Feb 13:e14545. doi: 10.1111/nmo.14545. Online ahead of print.ABSTRACTBACKGROUND: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS.METHODS: Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and quantitative measurement of TRP by mass spectrometry.RESULTS: Our cohort included 115 females, 69 with IBS and 46 HCs, with a mean age of 28.5 years (SD 7.4). TRP intake (p = 0.71) and stool TRP level (p = 0.27) did not differ between IBS and HC. Bifidobacterium abundance was lower in the IBS group than in HCs (p = 0.004). Predicted TRP metabolism gene content was higher in IBS than HCs (FDR-corrected q = 0.006), whereas predicted biosynthesis gene content was lower (q = 0.045). Within the IBS group, there was no association between symptom severity and TRP intake or stool TRP, but there was a significant interaction between Bifidobacterium abundance and TRP intake (q = 0.029) in predicting stool character.CONCLUSIONS: Dietary TRP intake, microbiome composition, and differences in TRP metabolism constitute a complex interplay of factors that could modulate IBS symptom severity.PMID:36780542 | DOI:10.1111/nmo.14545

Neurogastroenterol Motil. 2023 Feb 13:e14536. doi: 10.1111/nmo.14536. Online ahead of print.ABSTRACTBACKGROUND: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disease characterized by intermittent abdominal pain with altered bowel habits. Due to the condition's chronicity, patients suffer from poor quality of life, while the healthcare burden continues to grow. There is currently no reliable biomarker for the diagnosis of IBS, and the current approach depends on ruling-out organic diseases such as inflammatory bowel disease (IBD) and colorectal cancer by markers of inflammation like fecal calprotectin and C-reactive protein, or invasive procedures like a colonoscopy. Volatile organic compounds (VOCs) are growing in popularity as a biomarker due to its accuracy and ease of use.PURPOSE: This systematic review of Medline and Cochrane's databases aimed to identify VOCs in the diagnosis of IBS. 57% of the studies proved that VOCs could identify IBS patients from healthy controls with AUC ranging from 0.83 to 0.99. Studies that distinguished IBS from IBD patients had slightly higher AUC of 0.87-0.98. Combining VOC into panels allowed the creation of discriminative algorithms. Though current research is limited by areas of heterogeneity in VOC sampling and small sample sizes, our review shows that VOC analysis has the potential to be a noninvasive point-of-care test that differentiates IBS from other organic gastrointestinal diseases.PMID:36780514 | DOI:10.1111/nmo.14536

PLoS One. 2023 Feb 13;18(2):e0280883. doi: 10.1371/journal.pone.0280883. eCollection 2023.ABSTRACTOrgan-on-a-chip platforms are utilized in global bioanalytical and toxicological studies as a way to reduce materials and increase throughput as compared to in vivo based experiments. These platforms bridge the infrastructure and regulatory gaps between in vivo animal work and human systems, with models that exemplify active biological pathways. In conjunction with the advent of increased capabilities associated with next generation sequencing and mass spectrometry based '-omic' technologies, organ-on-a-chip platforms provide an excellent opportunity to investigate the global changes at multiple biological levels, including the transcriptome, proteome and metabolome. When investigated concurrently, a complete profile of cellular and regulatory perturbations can be characterized following treatment with specific agonists. In this study, global effects were observed and analyzed following liver chip exposure to the chemical warfare agent, VX. Even though the primary mechanism of action of VX (i.e. acetylcholinesterase inhibition) is well characterized, recent in vivo studies suggest additional protein binding partners that are implicated in metabolism and cellular energetic pathways. In addition, secondary toxicity associated with peripheral organ systems, especially in human tissues, is not well defined. Our results demonstrate the potential of utilizing an organ-on-a-chip platform as a surrogate system to traditional in vivo studies. This is realized by specifically indicating significant dysregulation of several cellular processes in response to VX exposure including but not limited to amino acid synthesis, drug metabolism, and energetics pathways.PMID:36780485 | DOI:10.1371/journal.pone.0280883

J Agric Food Chem. 2023 Feb 13. doi: 10.1021/acs.jafc.2c07162. Online ahead of print.ABSTRACTCommonalities in adaptive responses to abiotic stressors could contribute to the development of cross-resistance in weeds. The degree to which herbicide-induced changes in weeds parallel those induced by other abiotic stress remains unknown. We investigated the specificity of metabolic perturbations induced by glyphosate and drought across three glyphosate-resistant (GR) and two glyphosate-susceptible (GS) biotypes of Palmer amaranth (Amaranthus palmeri) using global metabolomics approaches. Compared to GS-biotypes, in the absence of stress, the GR-biotypes had a higher abundance of primary metabolites, including sugars, nonaromatic amino acids, and organic acids. However, despite having a higher 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene copy number that could upregulate the phenylpropanoid metabolism, the nonstressed GR-biotypes were less abundant in specialized (secondary) metabolites. Under glyphosate stress, 80% of metabolites, including shikimate, that accumulated in GS-biotypes also increased in the GR-biotypes. However, glyphosate triggered the preferential accumulation of glycosides of dihydroxylated and methoxylated flavanols with higher antioxidant potential, and ferulic acid derivatives, specifically in GR-biotypes. The disruption of the shikimate pathway and the accumulation of phenylpropanoids upon glyphosate exposure suggest that the stress response of GR-biotypes could be partly induced. This differential response was less evident in other phytochemical classes and under drought, highlighting that the phytochemical responses are stress-specific rather than biotype-specific.PMID:36780332 | DOI:10.1021/acs.jafc.2c07162

JMIR Res Protoc. 2023 Feb 13;12:e39058. doi: 10.2196/39058.ABSTRACTBACKGROUND: Excessive dietary sodium intake is an independent risk factor for hypertension and cardiovascular disease (CVD). Despite the large body of evidence concerning the effects of dietary interventions on blood pressure (BP) and CVD outcomes, trials have often reported low adherence to decreased sodium intake, likely due in part to heterogeneous BP responses. To address the challenges, recent clinical findings suggested a precise and personalized dietary approach that seeks to deliver more preventive and practical dietary advice than the "one-size-fits-all" guidelines and weighs the personal risk of developing specific diseases.OBJECTIVE: The purpose of this pilot randomized controlled trial was to test the feasibility and preliminary efficacy of integrating the use of mobile technology and metabolomics with a low-sodium diet intervention in patients with hypertension to develop personalized low-sodium diet programs. Additionally, the study will examine the associations of urine metabolites with urinary sodium levels and BP control based on the hypothesis that targeted urine metabolites. In this report, we describe the design and protocol of the pilot trial.METHODS: A total of 40 patients with hypertension will be randomly assigned to either a 8-week low-sodium diet group (n=20) or a standard care group (n=20). Each week, intervention participants went through individual sessions with an interventionist via videoconferencing to discuss low-sodium diet regimens, patients' food choices, and BP tracks on mobile apps. The control group followed their usual care for hypertension management. All participants in both groups monitored diet and BP using mobile apps for 8 weeks. A 24-hour urinary sodium excretion for the estimation of dietary sodium intake, systolic, and diastolic BPs were measured at the baseline and at 8 weeks. The primary outcomes of this study include the feasibility of conducting a randomized controlled trial (RCT) by reporting recruitment, retention, and completion statistics. The preliminary effects of intervention will be tested by a generalized estimating equation model.RESULTS: This pilot RCT study was approved by the institutional review board at the University of Texas Health San Antonio in January 2021. The first participant was enrolled in April 2021, and currently, 26 participants were enrolled. All data collection is expected to conclude by March 2023, with data analysis and study results ready for reporting by December 2023. Findings from this pilot RCT will further guide the team in planning a future large-scale study.CONCLUSIONS: The findings of this proposed study will establish a comprehensive knowledge base for future research and development of personalized dietary interventions to promote adherence to dietary strategies and self-management of chronic disease using the Precision Health approach for millions of Americans who are struggling with uncontrolled hypertension.TRIAL REGISTRATION: ClinicalTrials.gov NCT04764253; https://clinicaltrials.gov/ct2/show/NCT04764253.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39058.PMID:36780210 | DOI:10.2196/39058

mBio. 2023 Feb 13:e0316822. doi: 10.1128/mbio.03168-22. Online ahead of print.ABSTRACTBacteria can adapt to stressful conditions through mutations affecting the RNA polymerase core subunits that lead to beneficial changes in transcription. In response to selection with rifampicin (RIF), mutations arise in the RIF resistance-determining region (RRDR) of rpoB that reduce antibiotic binding. These changes can also alter transcription and thereby have pleiotropic effects on bacterial fitness. Here, we studied the evolution of resistance in Bacillus subtilis to the synergistic combination of RIF and the β-lactam cefuroxime (CEF). Two independent evolution experiments led to the recovery of a single rpoB allele (S487L) that was able to confer resistance to RIF and CEF through a single mutation. Two other common RRDR mutations made the cells 32 times more sensitive to CEF (H482Y) or led to only modest CEF resistance (Q469R). The diverse effects of these three mutations on CEF resistance are correlated with differences in the expression of peptidoglycan (PG) synthesis genes and in the levels of two metabolites crucial in regulating PG synthesis, glucosamine-6-phosphate (GlcN-6-P) and UDP-N-acetylglucosamine (UDP-GlcNAc). We conclude that RRDR mutations can have widely varying effects on pathways important for cell wall biosynthesis, and this may restrict the spectrum of mutations that arise during combination therapy. IMPORTANCE Rifampicin (RIF) is one of the most valued drugs in the treatment of tuberculosis. TB treatment relies on a combination therapy and for multidrug-resistant strains may include β-lactams. Mutations in rpoB present a common route for emergence of resistance to RIF. In this study, using B. subtilis as a model, we evaluate the emergence of resistance for the synergistic combination of RIF and the β-lactam cefuroxime (CEF). One clinically relevant rpoB mutation conferred resistance to both RIF and CEF, whereas one other increased CEF sensitivity. We were able to link these CEF sensitivity phenotypes to accumulation of UDP-N-acetylglucosamine (UDP-GlcNAc), which feedback regulates GlmS activity and thereby peptidoglycan synthesis. Further, we found that higher CEF concentrations precluded the emergence of high RIF resistance. Collectively, these results suggest that multidrug treatment regimens may limit the available pathways for the evolution of antibiotic resistance.PMID:36779708 | DOI:10.1128/mbio.03168-22

Physiol Genomics. 2023 Feb 13. doi: 10.1152/physiolgenomics.00169.2022. Online ahead of print.ABSTRACTSex differences in energy metabolism during acute, sub-maximal exercise are well documented. Whether these sex differences influence metabolic and physiologic responses to sustained, physically demanding activities is not well characterized. This study aimed to identify sex differences within changes in the serum metabolome in relation to changes in body composition, physical performance, and endocrine status during a 17-day military training exercise. Blood was collected, and body composition and lower-body power were measured before and after the training on 72 cadets (18 women). Total daily energy expenditure (TDEE) was assessed in a subset throughout. TDEE was greater in men (4,085±482kcal/d) than women (2,982±472kcal/d, p<0.001), but not after adjustment for dry lean mass (DLM). Men tended to lose more DLM than women (-0.2[-0.3,-0.1] vs. -0.0[-0.0,0.0] kg, p=0.063, Cohen's d=0.50) and have greater reductions in lower body power (-244[-314,-174] vs. -130[-209,-51] Watts, p=0.085, d=0.49). Reductions in DLM and lower body power were correlated (r=0.325, p=0.006). Women demonstrated greater fat oxidation than men (Δfat mass/DLM: -0.20[-0.24,-0.17] vs. -0.15[-0.17,-0.13] kg, p=0.012, d=0.64). Metabolites within pathways of fatty acid, endocannabinoid, lysophospholipid, phosphatidylcholine, phosphatidylethanolamine, and plasmalogen metabolism increased in women relative to men. Independent of sex, changes in metabolites related to lipid metabolism were inversely associated with changes in body mass and positively associated with changes in endocrine and metabolic status. These data suggest that during sustained military training, women preferentially mobilize fat stores compared with men, which may be beneficial for mitigating loss of lean mass and lower body power.PMID:36779667 | DOI:10.1152/physiolgenomics.00169.2022

New Phytol. 2023 Feb 13. doi: 10.1111/nph.18666. Online ahead of print.ABSTRACTChromatin is a dynamic platform within which gene expression is controlled by epigenetic modifications, notably targeting amino acid residues of histone H3. Among them is lysine 27 of H3 (H3K27), the trimethylation of which by the Polycomb Repressive Complex 2 (PRC2) is instrumental in regulating spatiotemporal patterns of key developmental genes. H3K27 is also subjected to acetylation and is found at sites of active transcription. Most information on the function of histone residues and their associated modifications in plants was obtained from studies of loss-of-function mutants for the complexes that modify them. To decrypt the genuine function of H3K27, we expressed a non-modifiable variant of H3 at residue K27 (H3.3K27A ) in Arabidopsis, and developed a multi-scale approach combining in-depth phenotypical and cytological analyses, with transcriptomics and metabolomics. We uncovered that the H3.3K27A variant causes severe developmental defects, part of them are reminiscent of PRC2 mutants, part of them are new. They include early flowering, increased callus formation and short stems with thicker xylem cell layer. This latest phenotype correlates with mis-regulation of phenylpropanoid biosynthesis. Overall, our results reveal novel roles of H3K27 in plant cell fates and metabolic pathways, and highlight an epigenetic control point for elongation and lignin composition of the stem.PMID:36779574 | DOI:10.1111/nph.18666

AIDS. 2023 Feb 9. doi: 10.1097/QAD.0000000000003512. Online ahead of print.ABSTRACTOBJECTIVE: :Why people living with HIV-1 on ART (PLWHART) display convoluted metabolism and immune cell functions during prolonged suppressive therapy is not well evaluated. In this study, we aimed to address this question using multiomics methodologies to investigate immunological and metabolic differences between PLWHART and HIV-1 negative individuals (HC).DESIGN: :Cross-sectional study.METHODS: :Untargeted and targeted metabolomics was performed using gas and liquid chromatography/mass spectrometry, and targeted proteomics using OlinkTM inflammation panel on plasma samples. The cellular metabolic state was further investigated using flow cytometry and intracellular metabolic measurement in single-cell populations isolated by EasySep cell isolation. Finally, flow cytometry was performed for deep-immunophenotyping of mononuclear phagocytes.RESULTS: :We detected increased levels of glutamate, lactate, and pyruvate by plasma metabolomics and increased inflammatory markers (e.g., CCL20 and CCL7) in PLWHART compared to HC. The metabolite transporter detection by flow cytometry in T-cells and monocytes indicated an increased expression of glucose transporter 1 (Glut1) and monocarboxylate transporter 1 (MCT-1) in PLWHART. Single cell-type metabolite measurement identified decreased glucose, glutamate, and lactate in monocytic cell populations in PLWHART. Deep-immunophenotyping of myeloid cell lineages subpopulations showed no difference in cell frequency, but expression levels of CCR5 were increased on classical monocytes and some dendritic cells.CONCLUSIONS: :Our data thus suggest that the myeloid cell populations potentially contribute significantly to the modulated metabolic environment during suppressive HIV-1 Infection.PMID:36779490 | DOI:10.1097/QAD.0000000000003512

J Sep Sci. 2023 Feb 13:e2200792. doi: 10.1002/jssc.202200792. Online ahead of print.ABSTRACTThe processing of Traditional Chinese Medicine requires the appropriate parameters, while the specific chemical markers are still absent to obtain the optimized processing. In this study, we used vinegar-baked Euphorbia kansui as a case to dissect the chemical markers for the baking-process using untargeted metabolomics. The robust chemical markers were selected based on the three rules, correlation, significant difference, and controllability. All the differential features were categorized based on their mass defects. After the differential analysis, 310 differential compounds were screened out and could be mainly divided into six categories: diacylglycerols and triacylglycerols demonstrated increasing trends with the baking time in the discriminant model, while ingenane-type diterpenes, jatrophane-type diterpenes, fatty acid esters, and fatty acids had decreasing trends. It was unexpected to find that the diterpenes did not correlate with the baking time. Only very few compounds meet the three rules. They were validated with an HPLC method. Finally, only 13-Hydroxy-9,11-octadecadienoic acid and its isomer 9-Hydroxy-10,12-octadecadienoic acid could be used further to differentiate the commercial vinegar-baked Euphorbia kansui. It would be of interest to evaluate whether these two compounds could be utilized as markers to control more processing methods in future studies. This article is protected by copyright. All rights reserved.PMID:36779441 | DOI:10.1002/jssc.202200792

Front Cell Infect Microbiol. 2023 Jan 26;13:1066053. doi: 10.3389/fcimb.2023.1066053. eCollection 2023.ABSTRACTBACKGROUND: Lingguizhugan decoction is a traditional Chinese medicine prescription that has been used to improve non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and underlying mechanisms of Lingguizhugan decoction remain unclear.METHODS: Male Sprague-Dawley rats were fed a methionine- and choline-deficient (MCD) diet to induce NASH, and then given Lingguizhugan decoction orally for four weeks. NASH indexes were evaluated by histopathological analysis and biochemical parameters including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver triglycerides (TG), etc. Fecal samples of rats were subjected to profile the changes of gut microbiota and metabolites using 16S rRNA sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS). Bioinformatics was used to identify Lingguizhugan decoction reversed candidates, and Spearman's correlation analysis was performed to uncover the relationship among gut microbiota, fecal metabolites, and NASH indexes.RESULTS: Four-week Lingguizhugan decoction treatment ameliorated MCD diet-induced NASH features, as evidenced by improved hepatic steatosis and inflammation, as well as decreased serum AST and ALT levels. Besides, Lingguizhugan decoction partially restored the changes in gut microbial community composition in NASH rats. Meanwhile, the relative abundance of 26 genera was significantly changed in NASH rats, and 11 genera (such as odoribacter, Ruminococcus_1, Ruminococcaceae_UCG-004, etc.) were identified as significantly reversed by Lingguizhugan decoction. Additionally, a total of 99 metabolites were significantly altered in NASH rats, and 57 metabolites (such as TDCA, Glutamic acid, Isocaproic acid, etc.) enriched in different pathways were reversed by Lingguizhugan decoction. Furthermore, Spearman's correlation analyses revealed that most of the 57 metabolites were significantly correlated with 11 genera and NASH indexes.CONCLUSION: Lingguizhugan decoction may exert protective effects on NASH partially by modulating gut microbiota and correlated metabolites.PMID:36779187 | PMC:PMC9908757 | DOI:10.3389/fcimb.2023.1066053

Expert Rev Precis Med Drug Dev. 2022;7(1):4-16. doi: 10.1080/23808993.2022.2028548. Epub 2022 Jan 24.ABSTRACTINTRODUCTION: Cardiovascular disease persists as the leading cause of death worldwide despite continued advances in diagnostics and therapeutics. Our current approach to patients with cardiovascular disease is rooted in reductionism, which presupposes that all patients share a similar phenotype and will respond the same to therapy; however, this is unlikely as cardiovascular diseases exhibit complex heterogeneous phenotypes.AREAS COVERED: With the advent of high-throughput platforms for omics testing, phenotyping cardiovascular diseases has advanced to incorporate large-scale molecular data with classical history, physical examination, and laboratory results. Findings from genomics, proteomics, and metabolomics profiling have been used to define more precise cardiovascular phenotypes and predict adverse outcomes in population-based and disease-specific patient cohorts. These molecular data have also been utilized to inform drug efficacy based on a patient's unique phenotype.EXPERT OPINION: Multiscale phenotyping of cardiovascular disease has revealed diversity among patients that can be used to personalize pharmacotherapies and predict outcomes. Nonetheless, precision phenotyping for cardiovascular disease remains a nascent field that has not yet translated into widespread clinical practice despite its many potential advantages for patient care. Future endeavors that demonstrate improved pharmacotherapeutic responses and associated reduction in adverse events will facilitate mainstream adoption of precision cardiovascular phenotyping.PMID:36778892 | PMC:PMC9913616 | DOI:10.1080/23808993.2022.2028548

Front Microbiol. 2023 Jan 26;14:1080743. doi: 10.3389/fmicb.2023.1080743. eCollection 2023.ABSTRACTAs an important source of new drug molecules, secondary metabolites (SMs) produced by microorganisms possess important biological activities, such as antibacterial, anti-inflammatory, and hypoglycemic effects. However, the true potential of microbial synthesis of SMs has not been fully elucidated as the SM gene clusters remain silent under laboratory culture conditions. Herein, we evaluated the inhibitory effect of Staphylococcus aureus by co-culture of Eurotium amstelodami and three Bacillus species, including Bacillus licheniformis, Bacillus subtilis, and Bacillus amyloliquefaciens. In addition, a non-target approach based on ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) was used to detect differences in extracellular and intracellular metabolites. Notably, the co-culture of E. amstelodami and Bacillus spices significantly improved the inhibitory effect against S. aureus, with the combination of E. amstelodami and B. licheniformis showing best performance. Metabolomics data further revealed that the abundant SMs, such as Nummularine B, Lucidenic acid E2, Elatoside G, Aspergillic acid, 4-Hydroxycyclohexylcarboxylic acid, Copaene, and Pipecolic acid were significantly enhanced in co-culture. Intracellularly, the differential metabolites were involved in the metabolism of amino acids, nucleic acids, and glycerophospholipid. Overall, this work demonstrates that the co-culture strategy is beneficial for inducing biosynthesis of active metabolites in E. amstelodami and B. licheniformis.PMID:36778878 | PMC:PMC9909110 | DOI:10.3389/fmicb.2023.1080743