PubMed

Food Chem. 2022 Nov 21;405(Pt B):135015. doi: 10.1016/j.foodchem.2022.135015. Online ahead of print.ABSTRACTEffects of different cooking treatments including steaming (S), boiling (B), stir-frying (SF) and frying (F) on the sensory qualities and pigmented phytochemicals of "Guanghong" carrot were studied based on intelligent sensory technology and targeted metabolomics, with fresh carrot slices (R) as control. Results showed cooking treatments reduced the brightness, redness, yellowness, and color saturation, and h° was the core index reflecting consumers' preference for the color characteristics of cooked carrots. The overall acceptability of cooked carrots was higher than R, and S gave carrots the best taste. (E/Z)-phytoene, α-carotene and β-carotene were the most dominant carotenoids monomers. None of the four cooking methods resulted in a loss of total monomer carotenoids content (TMCC) in carrots. B and SF increased the contents of xanthophyll and carotene, respectively, while the carotenoid esters's content remained stable during cooking. SF significantly increased TMCC and the contents of γ-carotene, α-carotene and (E/Z)-phytoene (p < 0.05). Pel-3-O-glu was the most important anthocyanins monomer in "Guanghong" carrot.PMID:36436237 | DOI:10.1016/j.foodchem.2022.135015

Metabolomics. 2022 Nov 27;18(12):97. doi: 10.1007/s11306-022-01956-x.ABSTRACTINTRODUCTION: The structural identification of metabolites represents one of the current bottlenecks in non-targeted liquid chromatography-mass spectrometry (LC-MS) based metabolomics. The Metabolomics Standard Initiative has developed a multilevel system to report confidence in metabolite identification, which involves the use of MS, MS/MS and orthogonal data. Limitations due to similar or same fragmentation pattern (e.g. isomeric compounds) can be overcome by the additional orthogonal information of the retention time (RT), since it is a system property that is different for each chromatographic setup.OBJECTIVES: In contrast to MS data, sharing of RT data is not as widespread. The quality of data and its (re-)useability depend very much on the quality of the metadata. We aimed to evaluate the coverage and quality of this metadata from public metabolomics repositories.METHODS: We acquired an overview on the current reporting of chromatographic separation conditions. For this purpose, we defined the following information as important details that have to be provided: column name and dimension, flow rate, temperature, composition of eluents and gradient.RESULTS: We found that 70% of descriptions of the chromatographic setups are incomplete (according to our definition) and an additional 10% of the descriptions contained ambiguous and/or incorrect information. Accordingly, only about 20% of the descriptions allow further (re-)use of the data, e.g. for RT prediction. Therefore, we have started to develop a unified and standardized notation for chromatographic metadata with detailed and specific description of eluents, columns and gradients.CONCLUSION: Reporting of chromatographic metadata is currently not unified. Our recommended suggestions for metadata reporting will enable more standardization and automatization in future reporting.PMID:36436113 | DOI:10.1007/s11306-022-01956-x

Cell Death Dis. 2022 Nov 26;13(11):1001. doi: 10.1038/s41419-022-05450-z.ABSTRACTBiliary atresia (BA) is a cholestatic liver disease in neonates with devastating obstructive intrahepatic and extrahepatic biliary ducts. Owing to the lack of an early diagnostic marker and limited understanding of its pathogenesis, BA often leads to death within 2 years. Therefore, this study aimed to develop early diagnostic methods and investigate the underlying pathogenesis of liver injury in BA using metabolomics. Metabolomics and organoid combined energy metabolism analysis was used to obtain new insights into BA diagnosis and pathobiology using patient samples, mice liver organoids, and a zebrafish model. Metabolomics revealed that D-2-hydroxyglutarate (D-2-HG) levels were significantly elevated in the plasma and liver of patients with BA and closely correlated with liver injuries and impaired liver regeneration. D-2-HG suppressed the growth and expansion of liver organoids derived from the intrahepatic biliary ducts. The energy metabolism analysis demonstrated that D-2-HG inhibited mitochondrial respiration and ATP synthase; however, it increased aerobic glycolysis in organoids. In addition, D-2-HG exposure caused liver degeneration in zebrafish larvae. Mechanistically, D-2-HG inhibited the activation of protein kinase B and the mammalian target of rapamycin signaling. These findings reveal that D-2-HG may represent a novel noninvasive diagnostic biomarker and a potential therapeutic target for infants with BA.PMID:36435860 | DOI:10.1038/s41419-022-05450-z

Food Chem. 2022 Nov 12;405(Pt B):134936. doi: 10.1016/j.foodchem.2022.134936. Online ahead of print.ABSTRACTDynamics and correlations of quality attributes, microbial profiles, and flavor metabolites were systematically investigated during chili fermentation on multi-salinity-driven levels (8/13/18 %). Metabolomic analysis revealed that pre-fermentation contributed to acetic acid (10.16 mg/kg, 65.01 %) and biogenic amines (53.70 mg/kg, 70.43 %). While main- and post-fermentation accumulated lactic acid (48.33 mg/kg, 76.49 %). Metabolome-microbiome interactions revealed that dominant genera mediated by salt levels affected the distribution of 24 differential odorants in 54 aromatic compounds. Enterobacter, Klebsiella, Cronobacter, and Acinetobacter triggered the production of 121 mg/kg biogenic amines and 7 unpleasant flavors. 7 dominant genera including Leuconostoc, Lactococcus, Weissella, Lactobacillus, Candida, Pichia, and Kazachstania were correlated with spicy, fruity, and floral aromas. Interestingly, salt-acid alternation drove succession from Leuconostoc, Weissella, and Lactococcus to Lactobacillus and Pediococcus. Overall, microbial composition and function were metabolism-dependent patterns. These results provide insight into microbial succession and flavor formation during staged fermentation and promote to optimize quality of fermented chili.PMID:36435118 | DOI:10.1016/j.foodchem.2022.134936

Food Chem. 2022 Nov 17;405(Pt B):134988. doi: 10.1016/j.foodchem.2022.134988. Online ahead of print.ABSTRACTCitrus is a genus containing diverse edible species, among them Citrus aurantium L. is widely utilized while short of composition research. Herein, utilizing multiple liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approaches, we comprehensively characterized its components. We first systematized both LC and MS characteristics of polymethoxyflavones (PMFs), by which 13 PMFs were identified in C. aurantium, and their biosynthesis pathway was further established. Using derivatization-LC-MS targeted metabolomics approaches, 28 carbohydrates and 18 carboxylic acids were firstly found in C. aurantium. Combined with untargeted metabolomics method, total 147 compositions were characterized, among which 92 were firstly reported in C. aurantium. We further obtained their geographical features and sought out principal discriminative compounds. Moreover, typical biofunctions of C. aurantium from diverse regions were speculated using pharmacological platform and partly verified by experiments. The present study provided systematic component information for C. aurantium, which laid the foundation for its further exploitation as functional food.PMID:36435109 | DOI:10.1016/j.foodchem.2022.134988

Ultrason Sonochem. 2022 Nov 23;91:106239. doi: 10.1016/j.ultsonch.2022.106239. Online ahead of print.ABSTRACTThis study investigated the effects of ultrasonication treatment on the germination rate of brown rice. Brown rice grains were subjected to ultrasound (40 kHz/30 min) and then incubated for 36 h at 37 °C to germinate the seeds. Ultrasonic treatment increased the germination rate of brown rice by up to ∼28 % at 30 h. Transcriptomic and metabolomic analyses were performed to explore the mechanisms underlying the effect of ultrasonic treatment on the brown rice germination rate. Comparing the treated and control check samples, 867 differentially expressed genes (DEGs) were identified, including 638 upregulated and 229 downregulated), as well as 498 differentially accumulated metabolites (DAMs), including 422 up accumulated and 76 down accumulated. Multi-omics analysis revealed that the germination rate of brown rice was promoted by increased concentrations of low-molecular metabolites (carbohydrates and carbohydrate conjugates, fatty acids, amino acids, peptides, and analogues), and transcription factors (ARR-B, NAC, bHLH and AP2/EREBP families) as well as increased carbon metabolism. These findings provide new insights into the mechanisms of action of ultrasound in improving the brown rice germination rate and candidate DEGs and DAMs responsible for germination have been identified.PMID:36435087 | DOI:10.1016/j.ultsonch.2022.106239

Int Immunopharmacol. 2022 Nov 23;113(Pt B):109472. doi: 10.1016/j.intimp.2022.109472. Online ahead of print.ABSTRACTInflammatory bowel disease (IBD) is a kind of chronic inflammation that occurs in gastrointestinal tract, including Ulcerative colitis (UC) and Crohn's disease (CD). Although UC and CD are associated with intestinal inflammation and epithelial damage, they are quite different. The etiology of IBD has not been fully determined, but there is extensive evidence that its pathogenesis involves environmental, genetic, immune and microbial factors. The diagnosis and treatment of IBD is challenging due to its recurrent episodes and complex evolution. Metabolomics, as a new developing technology, can be used to qualitatively and quantitatively study small metabolic molecules in samples of patients, which include stool, urine, serum, plasma and tissues, and is increasingly valued in the diagnosis and treatment of IBD. This article sums up the recent progress of metabolomics in helping to diagnose and treat IBD diseases, hoping to provide biomarkers and new targets for the diagnosis and treatment of IBD. In addition, we present the limitations of the current study of metabolomics and highlight some solutions.PMID:36435058 | DOI:10.1016/j.intimp.2022.109472

Tissue Cell. 2022 Nov 21;80:101984. doi: 10.1016/j.tice.2022.101984. Online ahead of print.ABSTRACTDetermining myocardial infarction (MI) and mechanical asphyxia (MA) was one of the most challenging tasks in forensic practice. The present study aimed to investigate the potential of fatty acid (FAs) metabolism, and lipid alterations in determining MI and MA. MA and MI mouse models were constructed, and metabolic profiles were obtained by LC-MS-based untargeted metabolomics. The metabolic alterations were explored using the PCA, OPLS-DA, the Wilcoxon test, and fold change analysis. The contents of lipid droplets (LDs) were detected by the transmission scanning electron microscope and Oil red O staining. The immunohistochemical assay was performed to detect CD36 and dysferlin. The ceramide was assessed by LC-MS. PCA showed considerable differences in the metabolite profiles, and the well-fitting OPLS-DA model was developed to screen differential metabolites. Thereinto, 9 metabolites in the MA were reduced, while metabolites were up- and down-regulated in MI. The increased CD36 suggested that MI and MA could enhance the intake of FAs and disturb energy metabolism. The increased LDs, decreased dysferlin, and increased ceramide (C18:0, C22:0, and C24:0) were observed in MI groups, confirming the lipid deposition. The present study indicated significant differences in myocardial FAs metabolism and lipid alterations between MI and MA, suggesting that FAs metabolism and related proteins, certain ceramide may harbor the potential as biomarkers for discrimination of MI and MA.PMID:36434828 | DOI:10.1016/j.tice.2022.101984

Chin Med. 2022 Nov 24;17(1):131. doi: 10.1186/s13020-022-00685-6.ABSTRACTBACKGROUND: Acute lung injury (ALI) is a severe inflammatory disease, underscoring the urgent need for novel treatments. Nauclea officinalis Pierre ex Pitard (Danmu in Chinese, DM) is effective in treating inflammatory respiratory diseases. However, there is still no evidence of its protective effect against ALI.METHODS: Metabolomics was applied to identify the potential biomarkers and pathways in ALI treated with DM. Further, network pharmacology was introduced to predict the key targets of DM against ALI. Then, the potential pathways and key targets were further verified by immunohistochemistry and western blot assays.RESULTS: DM significantly improved lung histopathological characteristics and inflammatory response in LPS-induced ALI. Metabolomics analysis showed that 16 and 19 differential metabolites were identified in plasma and lung tissue, respectively, and most of these metabolites tended to recover after DM treatment. Network pharmacology analysis revealed that the PI3K/Akt pathway may be the main signaling pathway of DM against ALI. The integrated analysis of metabolomics and network pharmacology identified 10 key genes. These genes are closely related to inflammatory response and cell apoptosis of lipopolysaccharide (LPS)-induced ALI in mice. Furthermore, immunohistochemistry and western blot verified that DM could regulate inflammatory response and cell apoptosis by affecting the PI3K/Akt pathway, and expression changes in Bax and Bcl-2 were also triggered.CONCLUSION: This study first integrated metabolomics, network pharmacology and biological verification to investigate the potential mechanism of DM in treating ALI, which is related to the regulation of inflammatory response and cell apoptosis. And the integrated analysis can provide new strategies and ideas for the study of traditional Chinese medicines in the treatment of ALI.PMID:36434729 | DOI:10.1186/s13020-022-00685-6

Lipids Health Dis. 2022 Nov 25;21(1):125. doi: 10.1186/s12944-022-01737-4.ABSTRACTBACKGROUND: Chronic nonspecific low back pain (cNLBP) is a common health problem worldwide, affecting 65-80% of the population and greatly affecting people's quality of life and productivity. It also causes huge economic losses. Manual therapy (MT) and therapeutic exercise (TE) are effective treatment options for cNLBP physiotherapy-based treatment. However, the underlying mechanisms that promote cNLBP amelioration by MT or TE are incompletely understood.METHODS: Seventeen recruited subjects were randomly divided into an MT group and a TE group. Subjects in the MT group performed muscular relaxation, myofascial release, and mobilization for 20 min during each treatment session. The treatment lasted for a total of six sessions, once every two days. Subjects in the TE group completed motor control and core stability exercises for 30 min during each treatment session. The motor control exercise included stretching of the trunk and extremity muscles through trunk and hip rotation and flexion training. Stabilization exercises consisted of the (1) bridge exercise, (2) single-leg-lift bridge exercise, (3) side bridge exercise, (4) two-point bird-dog position with an elevated contralateral leg and arm, (5) bear crawl exercise, and (6) dead bug exercise. The treatment lasted for a total of six sessions, with one session every two days. Serum samples were collected from subjects before and after physiotherapy-based treatment for lipidomic and metabolomic measurements.RESULTS: Through lipidomic analysis, we found that the phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio decreased and the sphingomyelin/ceramide (SM/Cer) ratio increased in cNLBP patients after MT or TE treatment. In addition, eight metabolites enriched in pyrimidine and purine differed significantly in cNLBP patients who received MT treatment. A total of nine metabolites enriched in pyrimidine, tyrosine, and galactose pathways differed significantly in cNLBP patients after TE treatment during metabolomics analysis.CONCLUSION: Our study was the first to elucidate the alterations in the lipidomics and metabolomics of cNLBP physiotherapy-based treatment and can expand our knowledge of cNLBP physiotherapy-based treatment.PMID:36434687 | DOI:10.1186/s12944-022-01737-4

Anim Microbiome. 2022 Nov 24;4(1):60. doi: 10.1186/s42523-022-00212-w.ABSTRACTBACKGROUND: Probiotics have been reported to exhibit positive effects on host health, including improved intestinal barrier function, preventing pathogenic infection, and promoting nutrient digestion efficiency. These internal changes are reflected to the fecal microbiota composition and, bacterial metabolites production. In accordance, the application of probiotics has been broadened to industrial animals, including swine, which makes people to pursue better knowledge of the correlation between changes in the fecal microbiota and metabolites. Therefore, this study evaluated the effect of multi-strain probiotics (MSP) supplementation to piglets utilizing multiomics analytical approaches including metagenomics, culturomics, and metabolomics.RESULTS: Six-week-old piglets were supplemented with MSP composed of Lactobacillus isolated from the feces of healthy piglets. To examine the effect of MSP supplement, piglets of the same age were selected and divided into two groups; one with MSP supplement (MSP group) and the other one without MSP supplement (Control group). MSP feeding altered the composition of the fecal microbiota, as demonstrated by metagenomics analysis. The abundance of commensal Lactobacillus was increased by 2.39%, while Clostridium was decreased, which revealed the similar pattern to the culturomic approach. Next, we investigated the microbial metabolite profiles, specifically SCFAs using HPLC-MS/MS and others using GC-MS, respectively. MSP supplement elevated the abundance of amino acids, including valine, isoleucine and proline as well as the concentration of acetic acid. According to the correlation analyses, these alterations were found out to be crucial in energy synthesizing metabolism, such as branched-chain amino acid (BCAA) metabolism and coenzyme A biosynthesis. Furthermore, we isolated commensal Lactobacillus strains enriched by MSP supplement, and analyzed the metabolites and evaluated the functional improvement, related to tight junction from intestinal porcine enterocyte cell line (IPEC-J2).CONCLUSIONS: In conclusion, MSP administration to piglets altered their fecal microbiota, by enriching commensal Lactobacillus strains. This change contributed amino acid, acetic acid, and BCAA concentrations to be increased, and energy metabolism pathway was also increased at in vivo and in vitro. These changes produced by MSP supplement suggests the correlation between the various physiological energy metabolism functions induced by health-promoting Lactobacillus and the growth performance of piglets.PMID:36434671 | DOI:10.1186/s42523-022-00212-w

Metabolomics. 2022 Nov 25;18(12):96. doi: 10.1007/s11306-022-01953-0.ABSTRACTBACKGROUND AND AIMS: Exclusive enteral nutrition is recommended as a first-line treatment in active pediatric Crohn's Disease, but its mechanism of action is still not clear. We aimed to assess alterations in the metabolic profile of newly diagnosed pediatric Crohn's Disease patients before and during exclusive enteral nutrition therapy.METHODS: Plasma samples from 14 pediatric Crohn's Disease patients before and after 3-4 weeks on exclusive enteral nutrition were analyzed using mass spectrometry. T-test, fold change and orthogonal partial least squares discriminant analysis were used for mining significant features. Correlation analysis was performed between the annotated features and the weighted pediatric Crohn's disease activity index using Pearson r distance.RESULTS: Among the 13 compounds which decreased during exclusive enteral nutrition, most are related to diet, while one is a bacterial metabolite, Bacteriohopane-32,33,34,35-tetrol. The phosphatidic acid metabolite PA(15:1/18:0) was significantly reduced and correlated with the weighted pediatric Crohn's disease activity index. Lipids increased during exclusive enteral nutrition therapy included phosphatidylethanolamines; PE(24:1/24:1), PE(17:2/20:2) and one lactosylceramide; LacCer(d18:1/14:0).CONCLUSION: Food additives and other phytochemicals were the major metabolites, which decreased following the exclusion of a regular diet during exclusive enteral nutrition. An alteration in bacterial biomarkers may reflect changes in intestinal microbiota composition and metabolism. Thus, metabolomics provides an opportunity to characterize the molecular mechanisms of dietary factors triggering Crohn's Disease activity, and the mechanisms of action of exclusive enteral nutrition, thereby providing the basis for the development and evaluation of improved intervention strategies for prevention and treatment.PMID:36434414 | DOI:10.1007/s11306-022-01953-0

Mol Psychiatry. 2022 Nov 25. doi: 10.1038/s41380-022-01860-9. Online ahead of print.ABSTRACTAutism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathophysiological mechanisms are still unclear. Hypotheses suggest a role for glutamate dysfunctions in ASD development, but clinical studies investigating brain and peripheral glutamate levels showed heterogenous results leading to hypo- and hyper-glutamatergic hypotheses of ASD. Recently, studies proposed the implication of elevated mGluR5 densities in brain areas in the pathophysiology of ASD. Thus, our objective was to characterize glutamate dysfunctions in adult subjects with ASD by quantifying (1) glutamate levels in the cingulate cortex and periphery using proton magnetic resonance spectroscopy and metabolomics, and (2) mGluR5 brain density in this population and in a validated animal model of ASD (prenatal exposure to valproate) at developmental stages corresponding to childhood and adolescence in humans using positron emission tomography. No modifications in cingulate Glu levels were observed between individuals with ASD and controls further supporting the difficulty to evaluate modifications in excitatory transmission using spectroscopy in this population, and the complexity of its glutamate-related changes. Our imaging results showed an overall increased density in mGluR5 in adults with ASD, that was only observed mostly subcortically in adolescent male rats prenatally exposed to valproic acid, and not detected in the stage corresponding to childhood in the same animals. This suggest that clinical changes in mGluR5 density could reflect the adaptation of the glutamatergic dysfunctions occurring earlier rather than being key to the pathophysiology of ASD.PMID:36434055 | DOI:10.1038/s41380-022-01860-9

Sci Data. 2022 Nov 24;9(1):722. doi: 10.1038/s41597-022-01755-y.ABSTRACTPlasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for biological and computational experiments and integrative analyses revolving around primary illness, relapse illness, and subsequent disease and immune response patterns. Parasitological, clinical, haematological, immune response, and -omic datasets (transcriptomics, proteomics, metabolomics, and lipidomics) including metadata and computational results have been deposited in public repositories. The scope and depth of these datasets are unprecedented in studies of malaria, and they are projected to be a F.A.I.R., reliable data resource for decades.PMID:36433985 | DOI:10.1038/s41597-022-01755-y

J Exp Bot. 2022 Nov 26:erac464. doi: 10.1093/jxb/erac464. Online ahead of print.ABSTRACTJasminum sambac is a well-known plant for its attractive and exceptional flower fragrance, and the flowers are used to produce scented tea. Jasmonate (JA), an important plant hormone was first identified in Jasminum species. Jasmine plants contain abundant JA naturally, of which the molecular mechanisms of synthesis and accumulation are not clearly understood. Here, we report a telomere-to-telomere consensus assembly of double-petal J. sambac genome along with two haplotype-resolved genomes. We found that gain-and-loss, positive selection, and allelic specific expression of aromatic votatile related genes contributed to the stronger flower fragrance in double-petal J. sambac compared with single- and multi-petal jasmines. Through comprehensive comparative genomic, transcriptomic, and metabolomic analyses of double-petal J. sambac, we revealed the genetic basis of the production of aromatic volatiles, salicylic acid (SA) and the accumulation of JA under non-stress conditions. We identified several key genes associated with JA biosynthesis, and their non-stress related activities lead to extraordinarily high concentrations of JA in tissues. High JA synthesis coupled with low degradation in J. sambac results in the accumulation of plentiful JA under typical environmental conditions, similar accumulation mechanism of SA. This study offers important insights into the biology of J. sambac, and provides valuable genomic resources for further utilization of natural products.PMID:36433929 | DOI:10.1093/jxb/erac464

J Sci Food Agric. 2022 Nov 26. doi: 10.1002/jsfa.12357. Online ahead of print.ABSTRACTBACKGROUND: Food polysaccharide 1,3-β-D-glucan (OBG) has been shown to alleviate ulcerative colitis (UC) in a mouse model, but the underlying mechanisms remain unclear. Here, we aimed to study potential mechanisms involving interactions among gut microbiota, microbial metabolites, and host metabolic function.RESULTS: OBG alleviated colonic inflammation, barrier dysfunction, intestinal concentrations of short-chain fatty acids in mice with UC. In addition, the relative abundances of Muribaculaceae, Alistipes, Erysipelatoclostridium, and Blautia increased, while the abundances of Proteus, Lachnospiraceae, and Ruminococcus decreased within the gut microbiota upon OBG treatment. KEGG analyzes showed that intestinal enzymes altered upon OBG treatment were mainly enriched in sub-pathways of amino acid biosynthesis. Metabolomics analyses showed that L-tryptophan, L-tyrosine, L-phenylalanine and L-alanine increased, which were consistent with the predictive metabolism of gut microbiota. Correlation analysis and interaction networks highlighted gut microbiota (especially Lactobacillus, Parabacteroides, Proteus, and Blautia), metabolites (especially L-phenylalanine, L-tryptophan, L-tyrosine, and acetic acid), and metabolism (phenylalanine, tyrosine and tryptophan biosynthesis) that may be key targets of OBG.CONCLUSION: OBG is beneficial to the gut microecological balance in mice with colitis, mainly due to its impact on the interactions between gut microbes and amino acids metabolism (especially tyrosine and tryptophan metabolism). This article is protected by copyright. All rights reserved.PMID:36433918 | DOI:10.1002/jsfa.12357

Artif Cells Nanomed Biotechnol. 2022 Dec;50(1):322-330. doi: 10.1080/21691401.2022.2124517.ABSTRACTThe small diameter crystalline silica is inhaled into the lung and cannot be cleared. As a result, the patient suffers from silicosis, a lung disease for which there is no effective treatment except lung transplantation. The aim of this study is to reveal the histological, cytological and metabolic characteristics of mice with pulmonary fibrosis induced by different doses of silica, and to provide an ideal animal model for drug development and disease research of pulmonary fibrosis. The experimental mice were divided into five groups. The mice were sacrificed 42 d later by nasal inhalation of normal saline and suspension containing silica 1 mg, 2 mg, 4 mg and 8 mg. Lung specimens and bronchoalveolar lavage fluid (BALF) were collected for histological and cytological examination. Carotid blood was collected and centrifuged to obtain serum for UHPLC-QE-MS non-target metabolomics detection. Compared with the normal control group, except 1 mg silica group, the other dosage groups showed different degree of disease characteristics. Metabolomics analysis showed that arginine and proline metabolism, pentose phosphate pathway, histidine metabolism, cysteine and methionine metabolism, ascorbic acid and aldoglucose metabolism were important metabolic pathways. This study reveals the histological, cytological and metabolic features of four-dose-gradient silica-induced pulmonary fibrosis mouse models.PMID:36433777 | DOI:10.1080/21691401.2022.2124517

Drug Dev Res. 2022 Nov 25. doi: 10.1002/ddr.22012. Online ahead of print.ABSTRACTRab GTPases are critical regulators of protein trafficking in the cell. To ensure proper cellular localization and function, Rab proteins must undergo a posttranslational modification, termed geranylgeranylation. In the isoprenoid biosynthesis pathway, the enzyme geranylgeranyl diphosphate synthase (GGDPS) generates the 20-carbon isoprenoid donor (geranylgeranyl pyrophosphate [GGPP]), which is utilized in the prenylation of Rab proteins. We have pursued the development of GGDPS inhibitors (GGSI) as a novel means to target Rab activity in cancer cells. Osteosarcoma (OS) and Ewing sarcoma (ES) are aggressive childhood bone cancers with stagnant survival statistics and limited treatment options. Here we show that GGSI treatment induces markers of the unfolded protein response (UPR) and triggers apoptotic cell death in a variety of OS and ES cell lines. Confirmation that these effects were secondary to cellular depletion of GGPP and disruption of Rab geranylgeranylation was confirmed via experiments using exogenous GGPP or specific geranylgeranyl transferase inhibitors. Furthermore, GGSI treatment disrupts cellular migration and invasion in vitro. Metabolomic profiles of OS and ES cell lines identify distinct changes in purine metabolism in GGSI-treated cells. Lastly, we demonstrate that GGSI treatment slows tumor growth in a mouse model of ES. Collectively, these studies support further development of GGSIs as a novel treatment for OS and ES.PMID:36433690 | DOI:10.1002/ddr.22012

Plants (Basel). 2022 Nov 12;11(22):3067. doi: 10.3390/plants11223067.ABSTRACTThe integrated analysis of different omic layers can provide new knowledge not provided by their individual analysis. This approach is also necessary to validate data and reveal post-transcriptional and post-translational mechanisms of gene expression regulation. In this work, we validated the possibility of applying this approach to non-model species such as Quercus ilex. Transcriptomics, proteomics, and metabolomics from Q. ilex seedlings subjected to drought-like conditions under the typical summer conditions in southern Spain were integrated using a non-targeted approach. Two integrative approaches, PCA and DIABLO, were used and compared. Both approaches seek to reduce dimensionality, preserving the maximum information. DIABLO also allows one to infer interconnections between the different omic layers. For easy visualization and analysis, these interconnections were analyzed using functional and statistical networks. We were able to validate results obtained by analyzing the omic layers separately. We identified the importance of protein homeostasis with numerous protease and chaperones in the networks. We also discovered new key processes, such as transcriptional control, and identified the key function of transcription factors, such as DREB2A, WRKY65, and CONSTANS, in the early response to drought.PMID:36432796 | DOI:10.3390/plants11223067

Plants (Basel). 2022 Nov 8;11(22):3014. doi: 10.3390/plants11223014.ABSTRACTLeaves of sweetpotato (Ipomoea batatas L.) are promising healthy leafy vegetable. Juvenile red fading (JRF) leaves of sweetpotato, with anthocyanins in young leaves, are good candidates for developing functional vegetables. Here, metabolic profiling and possible antioxidants were analyzed for five leaf stages of the sweetpotato cultivar "Chuanshan Zi". The contents of anthocyanins, total phenolics, and flavonoids all declined during leaf maturation, corresponding to declining antioxidant activities. By widely targeted metabolomics, we characterized 449 metabolites belonging to 23 classes. A total of 193 secondary metabolites were identified, including 82 simple phenols, 85 flavonoids, 18 alkaloids, and eight terpenes. Analysis of the metabolic data indicates that the antioxidant capacity of sweetpotato leaves is the combined result of anthocyanins and many other colorless compounds. Increased levels of "chlorogenic acid methyl ester", a compromised form of chlorogenic acid, significantly correlated with the declined antioxidant abilities. Besides anthocyanins, some significant metabolites contributing to the high antioxidant property of the sweetpotato leaves were highlighted, including chlorogenic acids, isorhamnetin glycosides, trans-4-hydroxycinnamic acid methyl ester, 4-methoxycinnamic acid, esculetin, caffeate, and trigonelline. This study provides metabolic data for the utilization of sweetpotato leaves as food sources, and sheds light on the metabolomic change for JRF leaves of other plants.PMID:36432744 | DOI:10.3390/plants11223014