PubMed

Metabolomics. 2023 Dec 8;20(1):4. doi: 10.1007/s11306-023-02063-1.ABSTRACTINTRODUCTION: Roses are one of the most essential ornamental flowers and are commonly used in perfumery, cosmetics, and food. They are rich in bioactive compounds, which are of interest for therapeutic effects.OBJECTIVES: The objective of this study was to understand the kinds of changes that occur between the nocturnal and diurnal metabolism of rose and to suggest hypotheses.METHODS: Reversed-phase ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry or triple quadrupole mass spectrometry (TQ MS/MS) was used for nontargeted metabolomics and hormonal profiling respectively. For metabolite annotation, accurate mass spectra were compared with those in databases.RESULTS: The hormonal profile of flowers showed an increase in jasmonate at night, while that of leaves indicated an increase in the salicylic acid pathway. Nontargeted analyses of the flower revealed a switch in the plant's defense mechanisms from glycosylated metabolites during the day to acid metabolites at night. In leaves, a significant decrease in flavonoids was observed at night in favor of acid metabolism to maintain a level of protection. Moreover, it might be possible to place back some of the annotated molecules on the shikimate pathway.CONCLUSION: The influence of day and night on the metabolome of rose flowers and leaves has been clearly demonstrated. The hormonal modulations occurring during the night and at day are consistent with the plant circadian cycle. A proposed management of the sesquiterpenoid and triterpenoid biosynthetic pathway may explain these changes in the flower. In leaves, the metabolic differences may reflect night-time regulation in favor of the salicylic acid pathway.PMID:38066353 | DOI:10.1007/s11306-023-02063-1

Nat Med. 2023 Dec 8. doi: 10.1038/s41591-023-02644-6. Online ahead of print.ABSTRACTThe glial environment influences neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models of traumatic brain injury, beneficial functions of proliferating reactive astrocytes on disease outcome have been unraveled, but little is known regarding if and when they are present in human brain pathology. Here we examined a broad spectrum of pathologies with and without intracerebral hemorrhage and found a striking correlation between lesions involving blood-brain barrier rupture and astrocyte proliferation that was further corroborated in an assay probing for neural stem cell potential. Most importantly, proteomic analysis unraveled a crucial signaling pathway regulating this astrocyte plasticity with GALECTIN3 as a novel marker for proliferating astrocytes and the GALECTIN3-binding protein LGALS3BP as a functional hub mediating astrocyte proliferation and neurosphere formation. Taken together, this work identifies a therapeutically relevant astrocyte response and their molecular regulators in different pathologies affecting the human cerebral cortex.PMID:38066208 | DOI:10.1038/s41591-023-02644-6

Nat Metab. 2023 Dec 8. doi: 10.1038/s42255-023-00936-2. Online ahead of print.ABSTRACTSerine is a vital amino acid in tumorigenesis. While cells can perform de novo serine synthesis, most transformed cells rely on serine uptake to meet their increased biosynthetic requirements. Solute carriers (SLCs), a family of transmembrane nutrient transport proteins, are the gatekeepers of amino acid acquisition and exchange in mammalian cells and are emerging as anticancer therapeutic targets; however, the SLCs that mediate serine transport in cancer cells remain unknown. Here we perform an arrayed RNAi screen of SLC-encoding genes while monitoring amino acid consumption and cell proliferation in colorectal cancer cells using metabolomics and high-throughput imaging. We identify SLC6A14 and SLC25A15 as major cytoplasmic and mitochondrial serine transporters, respectively. We also observe that SLC12A4 facilitates serine uptake. Dual targeting of SLC6A14 and either SLC25A15 or SLC12A4 diminishes serine uptake and growth of colorectal cancer cells in vitro and in vivo, particularly in cells with compromised de novo serine biosynthesis. Our results provide insight into the mechanisms that contribute to serine uptake and intracellular handling.PMID:38066114 | DOI:10.1038/s42255-023-00936-2

Cell Death Dis. 2023 Dec 8;14(12):810. doi: 10.1038/s41419-023-06294-x.ABSTRACTFerroptosis, which is driven by iron-dependent lipid peroxidation, plays an essential role in liver ischemia-reperfusion injury (IRI) during liver transplantation (LT). Gp78, an E3 ligase, has been implicated in lipid metabolism and inflammation. However, its role in liver IRI and ferroptosis remains unknown. Here, hepatocyte-specific gp78 knockout (HKO) or overexpressed (OE) mice were generated to examine the effect of gp78 on liver IRI, and a multi-omics approach (transcriptomics, proteomics, and metabolomics) was performed to explore the potential mechanism. Gp78 expression decreased after reperfusion in LT patients and mice with IRI, and gp78 expression was positively correlated with liver damage. Gp78 absence from hepatocytes alleviated liver damage in mice with IRI, ameliorating inflammation. However, mice with hepatic gp78 overexpression showed the opposite phenotype. Mechanistically, gp78 overexpression disturbed lipid homeostasis, remodeling polyunsaturated fatty acid (PUFA) metabolism, causing oxidized lipids accumulation and ferroptosis, partly by promoting ACSL4 expression. Chemical inhibition of ferroptosis or ACSL4 abrogated the effects of gp78 on ferroptosis and liver IRI. Our findings reveal a role of gp78 in liver IRI pathogenesis and uncover a mechanism by which gp78 promotes hepatocyte ferroptosis by ACSL4, suggesting the gp78-ACSL4 axis as a feasible target for the treatment of IRI-associated liver damage.PMID:38065978 | DOI:10.1038/s41419-023-06294-x

Clin Immunol. 2023 Dec 6:109861. doi: 10.1016/j.clim.2023.109861. Online ahead of print.ABSTRACTWith increasing stress in daily life and work, subhealth conditions induced by "Shi-Re Shanghuo" syndrome was gradually universal. "Huanglian Jiedu Wan" (HLJDW) was the first new syndrome Chinese medicine approved for the treatment of "Shi-Re Shanghuo" with promising clinical efficacy. Preliminary small-sample clinical studies have identified some notable biomarkers (succinate, 4-hydroxynonenal, etc.). However, the correlation and underlying mechanism between these biomarkers of HLJDW intervention on "Shi-Re Shanghuo" syndrome remained ambiguous. Therefore, this study was designed as a randomized, double-blind, multicenter, placebo-controlled Phase II clinical trial, employing integrated analysis techniques such as non-targeted and targeted metabolomics, salivary microbiota, proteomics, parallel peaction monitoring, molecular docking and surface plasmon resonance (SPR). The results of the correlation analysis indicated that HLJDW could mediate the balance between inflammation and immunity through succinate produced via host and microbial source to intervene "Shi-Re Shanghuo" syndrome. Further through the HIF1α/MMP9 pathway, succinate regulated downstream arachidonic acid metabolism, particularly the lipid peroxidation product 4-hydroxynonenal. Finally, an animal model of recurrent oral ulcers induced by "Shi-Re Shang Huo" was established and HLJDW was used for intervention, key essential indicators (succinate, glutamine, 4-hydroxynonenal, arachidonic acid metabolism) essential in the potential pathway HIF1α/MMP9 discovered in clinical practice were validated. The results were found to be consistent with our clinical findings. Taken together, succinate was observed as an important signal that triggered immune responses, which might serve as a key regulatory metabolic switch or marker of "Shi-Re Shanghuo" syndrome treated with HLJDW.PMID:38065370 | DOI:10.1016/j.clim.2023.109861

Plant Physiol Biochem. 2023 Nov 30;206:108245. doi: 10.1016/j.plaphy.2023.108245. Online ahead of print.ABSTRACTEffective colonization on plant roots is a prerequisite for plant growth promoting rhizobacterias (PGPR) to exert beneficial activities. Light is essential for plant growth, development and stress response. However, how light modulates root colonization of PGPR remains unclear. Here, we found that high red/far red (R/FR) light promoted and low R/FR light inhibited the colonization and growth enhancement of Serratia plymuthica A21-4 (S. plymuthica A21-4) on tomato, respectively. Non-targeted metabolomic analysis of root exudates collected from different R/FR ratio treated tomato seedlings with or without S. plymuthica A21-4 inoculation by UPLC-MS/MS showed that 64 primary metabolites in high R/FR light-grown plants significantly increased compared with those determined for low R/FR light-grown plants. Among them, 7 amino acids, 1 organic acid and 1 sugar obviously induced the chemotaxis and biofilm formation of S. plymuthica A21-4 compared to the control. Furthermore, exogenous addition of five artificial root exudate compontents (leucine, methionine, glutamine, 6-aminocaproic acid and melezitose) regained and further increased the colonization ability and growth promoting ability of S. plymuthica A21-4 on tomato under low R/FR light and high R/FR light, respectively, indicating their involvement in high R/FR light-regulated the interaction of tomato root and S. plymuthica A21-4. Taken together, our results, for the first time, clearly demonstrate that high R/FR light-induced root exudates play a key role in chemotaxis, biofilm formation and root colonization of S. plymuthica A21-4. This study can help promote the combined application of light supplementation and PGPR to facilitate crop growth and health in green agricultural production.PMID:38064903 | DOI:10.1016/j.plaphy.2023.108245

Plant Physiol Biochem. 2023 Dec 5;206:108257. doi: 10.1016/j.plaphy.2023.108257. Online ahead of print.ABSTRACTOcean warming (OW) and ocean acidification (OA), driven by rapid global warming accelerating at unprecedented rates, are profoundly impacting the stability of seagrass ecosystems. Yet, our current understanding of the effects of OW and OA on seagrass remains constrained. Herein, we investigated the response of eelgrass (Zostera marina L.), a representative seagrass species, to OW and OA through comprehensive transcriptomic and metabolomic analyses. The results showed notable variations in plant performance under varying conditions: OW, OA, and OWA (a combination of both conditions). Specifically, under average oceanic temperature conditions for eelgrass growth over the past 20 years -from May to November-OA promoted the production of differentially expressed genes and metabolites associated with alanine, aspartate, and glutamate metabolism, as well as starch and sucrose metabolism. Under warming condition, eelgrass was resistant to OA by accelerating galactose metabolism, along with glycine, serine, and threonine metabolism, as well as the tricarboxylic acid (TCA) cycle. Under the combined OW and OA condition, eelgrass stimulated fructose and mannose metabolism, glycolysis, and carbon fixation, in addition to galactose metabolism and the TCA cycle to face the interplay. Our findings suggest that eelgrass exhibits adaptive capacity by inducing different metabolites and associated genes, primarily connected with carbon and nitrogen metabolism, in response to varying degrees of OW and OA. The data generated here support the exploration of mechanisms underlying seagrass responses to environmental fluctuations, which hold critical significance for the future conservation and management of these ecosystems.PMID:38064900 | DOI:10.1016/j.plaphy.2023.108257

Poult Sci. 2023 Nov 24;103(2):103288. doi: 10.1016/j.psj.2023.103288. Online ahead of print.ABSTRACTThis paper aimed to evaluate the effect of 3 kinds of TCM polysaccharides instead of antibiotics in preventing salpingitis in laying hens. After feeding the laying hens with Lotus leaf polysaccharide, Poria polysaccharide, and Epimedium polysaccharide, mixed bacteria (E. coli and Staphylococcus aureus) were used to infect the oviduct to establish an inflammation model. Changes in antioxidant, serum immunity, anti-inflammatory, gut microbiota, and serum metabolites were evaluated. The results showed that the 3 TCM polysaccharides could increase the expression of antioxidant markers SOD, GSH, and CAT, and reduce the accumulation of MDA in the liver; the contents of IgA and IgM in serum were increased. Decreased the mRNA expression of TLR4, NFκB, TNF-α, IFN-γ, IL1β, IL6, and IL8, and increased the mRNA expression of anti-inflammatory factor IL5 in oviduct tissue. 16sRNA high-throughput sequencing revealed that the 3 TCM polysaccharides improved the intestinal flora disturbance caused by bacterial infection, increased the abundance of beneficial bacteria such as Bacteroides and Actinobacillus, and decreased the abundance of harmful bacteria such as Romboutsia, Turicibacter, and Streptococcus. Metabolomics showed that the 3 TCM polysaccharides could increase the content of metabolites such as 3-hydroxybutyric acid and isobutyl-L-carnitine, and these results could alleviate the further development of salpingitis. In conclusion, the present study has found that using TCM polysaccharides instead of antibiotics was a feasible way to prevent bacterial salpingitis in laying hens, which might make preventing this disease no longer an issue for breeding laying hens.PMID:38064885 | DOI:10.1016/j.psj.2023.103288

Animal. 2023 Nov 10;17(12):101029. doi: 10.1016/j.animal.2023.101029. Online ahead of print.ABSTRACTMetabolomics has been used to characterise many biological matrices and obtain detailed pictures of biological systems based on many metabolites. Plasma and serum are two blood-derived biofluids commonly used to assess and monitor the organismal metabolism and obtain information on the physiological and health conditions of an animal. Plasma is the supernatant that is separated from the cellular components after centrifugation of the blood that is first added with an anticoagulant. Serum is obtained after centrifugation of the blood that has been coagulated. The choice of one or the other biofluid for metabolomic analyses is related to specific analytical needs and technical issues, to problems derived by the collection and preparation steps, in particular when specimens are sampled from animals involved in field studies. Thus far, most of the metabolomic studies that compared plasma and serum have been carried out in humans and very little is known on the pigs. In this study, we used a targeted metabolomic platform that can detect about 180 metabolites of five biochemical classes to compare plasma and serum profiles of samples collected from 24 pigs. To also obtain a cross-species comparative metabolomic analysis, information for human plasma and serum derived from the same platform was retrieved from previous studies. Statistical analyses included univariate and multivariate approaches aimed at identifying stable and/or differentially abundant metabolites between the two porcine biofluids. A total of 154 (∼83%) metabolites passed the initial quality control, indicating a good repeatability of the analytical platform in pigs. Discarded metabolites included aspartate and biogenic amines that were already reported to be unstable in human studies. More than 80% of the metabolites had similar profiles in both porcine biofluids (average correlation was 0.75). Concentrations were usually higher in serum than in plasma, in agreement with what was already reported in humans. The univariate analysis identified 44 metabolites that had statistically different concentrations between porcine plasma and serum, of which 28 metabolites were also confirmed by the multivariate analysis. The obtained picture described similarities and differences between these two biofluids in pigs and the related human-pig comparisons. The obtained information can be useful for the choice of one or the other matrix for the implementation of metabolomic studies in this livestock species. The results can also provide useful hints to valuing the pig as animal model, in particular when metabolite-derived physiological states are relevant.PMID:38064856 | DOI:10.1016/j.animal.2023.101029

Food Chem. 2023 Dec 5;439:138133. doi: 10.1016/j.foodchem.2023.138133. Online ahead of print.ABSTRACTThis study was the first to comprehensively investigate the metabolic mechanism of flavonoid glycosides (FGs) and their contribution to flavor evolution during white tea processing using quantitative descriptive analysis, metabolomics, dose-over-threshold factors and pseudo-first-order kinetics. A total of 223 flavonoids were identified. Total FGs decreased from 7.02 mg/g to 4.35 mg/g during processing, compared to fresh leaves. A total of 86 FGs had a significant impact on the flavor evolution and 9 key flavor FGs were identified. The FG biosynthesis pathway was inhibited during withering, while the degradation pathway was enhanced. This promoted the degradation of 9 key flavor FGs following pseudo-first-order kinetics during withering. The degradation of the FGs contributed to increase the taste acceptance of white tea from -4.18 to 1.32. These results demonstrated that water loss stress during withering induces the degradation of key flavor FGs, contributing to the formation of the unique flavor of white tea.PMID:38064841 | DOI:10.1016/j.foodchem.2023.138133

J Pharm Biomed Anal. 2023 Dec 3;239:115900. doi: 10.1016/j.jpba.2023.115900. Online ahead of print.ABSTRACTThere is an accelerated progression of liver necroinflammation and fibrosis in the liver during the immune clearance (IC) phase of Chronic hepatitis B virus (HBV) infection, which are critical indicators of antiviral treatment for chronic hepatitis B (CHB) infection. This study applied serum metabolomics to identify the potential metabolite biomarkers for differential diagnosis between the CHB immune tolerance (IT) and Immune clearance (IC) phases. A liquid chromatography-mass spectrometry (LC-MS)-based approach was applied to evaluate and compared the serum metabolic profiles of 28 patients in IT phase and 33 patients in IC phase and appropriate statistical methods with MetaboAnalystR 2.0 R package to analyze those metabolites. The differential metabolites between IT and TC groups were classified and the top altered classification were lipids and lipid-like molecules and fatty acyls, clearly indicating that there were differences in the lipid metabolomic profile of HBV-infected patients with IT vs. IR phase. We identified the top 10 potential metabolite biomarkers for differential diagnosis between IT and IR. There were four lipid metabolites among them and the AUC of two of them, octadecadienoyl-sn-glycero-3-phosphocholine and 3-Cycloheptene-l-acetic acid, were 0.983 and 0.933. octadecadienoyl-sn-glycero-3-phosphocholine is Diacylglycerol (18:2n6/18:0) and 3-Cycloheptene-l-acetic acid is hydroxy fatty acids, both of which were associated with lipid metabolism. This study not only provides the potential metabolic biomarkers but also insight into the mechanism of CHB progression during IT clearance phase.PMID:38064772 | DOI:10.1016/j.jpba.2023.115900

J Pharm Biomed Anal. 2023 Dec 3;239:115869. doi: 10.1016/j.jpba.2023.115869. Online ahead of print.ABSTRACTHepatocellular carcinoma (HCC) is one of the most prevalent malignant cancers worldwide. Due to the asymptomatic features of HCC at early stages, patients are often diagnosed at advanced stages and missed effective treatment. Thus, there is an urgent need to identify sensitive and specific biomarkers for HCC early diagnosis. In the present study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) approach was used to profile serum metabolites from HCC patients, liver cirrhosis (LC) patients, and normal controls (NC). Univariate and multivariate statistical analyses were performed to obtain the metabolomic differences of the three groups and select significantly changed metabolites that can be used as diagnostic biomarkers. In total, 757 differential metabolites were quantified among the three groups, and pathway enrichment analysis of these metabolites indicated that glycerophospholipid metabolism, pentose and glucuronate interconversions, phenylalanine, tyrosine and tryptophan biosynthesis, and linoleic acid metabolism were the most altered pathways involved in HCC development. Receiver operating characteristic (ROC) curve analysis was performed to select and evaluate the diagnostic biomarker performance. Seven metabolites were identified as potential biomarkers that can differentiate HCC from LC and NC, and LC from NC with the good diagnostic performance of area under the curve (AUC) from 0.890 to 0.990. In summary, our findings provide highly effective biomarker candidates to differentiate HCC from LC and NC, LC, and NC, which shed insight into HCC pathological mechanisms and will be helpful in better understanding and managing HCC.PMID:38064771 | DOI:10.1016/j.jpba.2023.115869

J Anim Sci. 2023 Dec 8:skad395. doi: 10.1093/jas/skad395. Online ahead of print.ABSTRACTInfant mortality of low birth body weight (LBBW) piglets can reach 10% and is mainly due to gut and immune system immaturity which can lead to a higher risk in the long term. This study aimed to assess the impact of birth body weight (BBW) on piglet metabolism, gut status, and microbial profile from weaning to 21 days post-weaning. At birth, 32 piglets were selected for their BBW and inserted into the normal BBW (NBBW:1.38±0.09g) or the LBBW (0.92±0.07g) group. The piglets were weighed weekly from weaning (d0) to d21. At d9 and d21, 8 piglets/group were slaughtered to obtain the distal jejunum for morphology, immunohistochemistry and gene expression analysis, colon content for microbiota and short chain fatty acid (SCFA) analysis, and intestinal content for pH measurement. Blood was collected for metabolomic, haptoglobin (Hp), reactive oxygen metabolite (ROM) analysis. The LBBW group had a lower body weight (BW) throughout the study (P<0.01), a lower average daily gain from d9-d21 (P=0.002) and lower feed intake (P=0.02). The LBBW piglets had lower Hp at d9 (P=0.03), higher ROMs at d21 (P=0.06) and a net alteration of the amino acid (AA) metabolism at d9 and d21. A higher expression of NFKB2 was observed in the LBBW piglets at d9 (P=0.003) and d21 (P<0.001). MYD88 expression was enhanced in NBBW piglets at d9 (P<0.001). The LBBW piglets had a lower villus height, absorptive mucosal surface (P=0.01) and villus height:crypt depth ratio (P=0.02), and a greater number of T-lymphocytes in both the epithelium and the crypts (P<0.001) at d21. At d21, the LBBW piglets had higher lactic acid, acetate, butyrate and valerate, and also higher SCFA in the colon (P<0.05). The LBBW piglets had a higher Shannon index (P=0.01) at d9 and a higher abundance of SCFA-fermenting bacteria. In conclusion, the present study confirmed that LBBW could impact the gut mucosal structure, immunity, and inflammatory and oxidative status, leading to an altered AA metabolism, delaying the recovery from weaning.PMID:38064718 | DOI:10.1093/jas/skad395

J Agric Food Chem. 2023 Dec 8. doi: 10.1021/acs.jafc.3c04063. Online ahead of print.ABSTRACTThis study aims to explore the effects of Astragaloside IV (AS-IV) on abnormal behaviors, intestinal microbiota, intestinal T-immune balance, and fecal metabolism of a model of depression in rats. Herein, we integrally applied 16S rRNA sequencing, molecular biological techniques, and 1H NMR-based fecal metabolomics to demonstrate the antidepression activity of AS-IV. The results suggested that AS-IV regulated the depression-like behaviors of rats, which are presented by an increase of body weight, upregulation of sucrose preference rates, and a decrease of immobility time. Additionally, AS-IV increased the abundances of beneficial bacteria (Lactobacillus and Oscillospira) in a model of depression in rats. Moreover, AS-IV regulated significantly the imbalance of Th17/Treg cells, and the abnormal contents of both anti-inflammatory factors and pro-inflammatory factors. Besides, fecal metabolomics showed that AS-IV improved the abnormal levels of short-chain fatty acids and amino acids. Collectively, our research supplemented new data, supporting the potential of AS-IV as an effective diet or diet composition to improve depression-like behaviors, dysfunctions of microbiota, imbalance of T immune, and the abnormality of fecal metabolome. However, the causality of the other actions was not proven because of the experimental design and the methodology used. The current findings suggest that AS-IV could function as a promising diet or diet composition to alleviate depressed symptoms.PMID:38064688 | DOI:10.1021/acs.jafc.3c04063

Sci Adv. 2023 Dec 8;9(49):eade1370. doi: 10.1126/sciadv.ade1370. Epub 2023 Dec 8.ABSTRACTBacille Calmette-Guerin (BCG) vaccine can elicit good TH1 responses in neonates. We hypothesized that the pioneer gut microbiota affects vaccine T cell responses. Infants who are HIV exposed but uninfected (iHEU) display an altered immunity to vaccination. BCG-specific immune responses were analyzed at 7 weeks of age in iHEU, and responses were categorized as high or low. Bifidobacterium longum subsp. infantis was enriched in the stools of high responders, while Bacteroides thetaiotaomicron was enriched in low responders at time of BCG vaccination. Neonatal germ-free or SPF mice orally gavaged with live B. infantis exhibited significantly higher BCG-specific T cells compared with pups gavaged with B. thetaiotaomicron. B. infantis and B. thetaiotaomicron differentially affected stool metabolome and colonic transcriptome. Human colonic epithelial cells stimulated with B. infantis induced a unique gene expression profile versus B. thetaiotaomicron. We thus identified a causal role of B. infantis in early-life antigen-specific immunity.PMID:38064556 | DOI:10.1126/sciadv.ade1370

mSystems. 2023 Dec 8:e0080323. doi: 10.1128/msystems.00803-23. Online ahead of print.ABSTRACTThe metabolic profiles within microbial biofilms and interkingdom interactions are extremely complex and serve a variety of functions, which include promoting colonization, growth, and survival within competitive and symbiotic environments. However, measuring and differentiating many of these molecules, especially in an in situ fashion, remains a significant analytical challenge. We demonstrate a chemical derivatization strategy that enabled highly sensitive, multiplexed mass spectrometry imaging of over 300 metabolites from a model microbial co-culture. Notably, this approach afforded us to visualize over two dozen classes of ketone-, aldehyde-, and carboxyl-containing molecules, which were previously undetectable from colonies grown on agar. We also demonstrate that this chemical derivatization strategy can enable the discrimination of isobaric and isomeric metabolites without the need for orthogonal separation (e.g., online chromatography or ion mobility). We anticipate that this approach will further enhance our knowledge of metabolic regulation within microbiomes and microbial systems used in bioengineering applications.PMID:38064548 | DOI:10.1128/msystems.00803-23

J Proteome Res. 2023 Dec 8. doi: 10.1021/acs.jproteome.3c00566. Online ahead of print.ABSTRACTMitochondrial division inhibitor 1 (Mdivi-1) is a well-known synthetic compound aimed at inhibiting dynamin-related protein 1 (Drp1) to suppress mitochondrial fission, making it a valuable tool for studying mitochondrial dynamics. However, its specific effects beyond Drp1 inhibition remain to be confirmed. In this study, we employed integrative proteomics and phosphoproteomics to delve into the molecular responses induced by Mdivi-1 in SK-N-BE(2)C cells. A total of 3070 proteins and 1945 phosphorylation sites were identified, with 880 of them represented as phosphoproteins. Among these, 266 proteins and 97 phosphorylation sites were found to be sensitive to the Mdivi-1 treatment. Functional enrichment analysis unveiled their involvement in serine biosynthesis and extrinsic apoptotic signaling pathways. Through targeted metabolomics, we observed that Mdivi-1 enhanced intracellular serine biosynthesis while reducing the production of C24:1-ceramide. Within these regulated phosphoproteins, dynamic dephosphorylation of proteasome subunit alpha type 3 serine 250 (PSMA3-S250) occurred after Mdivi-1 treatment. Further site-directed mutagenesis experiments revealed that the dephosphorylation-deficient mutant PSMA3-S250A exhibited a decreased cell survival. This research confirms that Mdivi-1's inhibition of mitochondrial division leads to various side effects, ultimately influencing cell survival, rather than solely targeting Drp1 inhibition.PMID:38064546 | DOI:10.1021/acs.jproteome.3c00566

PLoS One. 2023 Dec 8;18(12):e0295592. doi: 10.1371/journal.pone.0295592. eCollection 2023.ABSTRACTO-coumaric acid (OCA), as a significant phenolic allelochemical found in hairy vetch (Vicia villosa Roth.), that can hinder the growth of alfalfa (Medicago sativa L.), particularly the growth of alfalfa roots. Nonetheless, the mechanism by which OCA inhibits alfalfa root growth remains unclear. In this study, a liquid chromatography tandem mass spectrometry (LC-MS/MS)-based quantitative proteomics analysis was carried out to identify differentially accumulated proteins (DAPs) under OCA treatment. The findings indicated that 680 proteins were DAPs in comparison to the control group. Of those, 333 proteins were up-regulated while 347 proteins were down-regulated. The enrichment analysis unveiled the significance of these DAPs in multiple biological and molecular processes, particularly in ribosome, phenylpropanoid biosynthesis, glutathione metabolism, glycolysis/gluconeogenesis and flavonoid biosynthesis. The majority of DAPs reside in the cytoplasm (36.62%), nucleus (20.59%) and extracellular space (14.12%). In addition, phenylalanine deaminase was identified as a potential chemical-induced regulation target associated with plant lignin formation. DAPs were mainly enriched in flavonoid biosynthesis pathways, which were related to plant root size. Using the UPLC-ESI-MS/MS technique and database, a total of 87 flavonoid metabolites were discovered. The metabolites were predominantly enriched for biosynthesizing naringenin chalcone, which was linked to plant lignin formation, aligning with the enrichment outcomes of DAPs. Consequently, it was deduced that OCA impacted the structure of cell walls by mediating the synthesis of lignin in alfalfa roots, subsequently inducing wilt. Furthermore, a range of proteins have been identified as potential candidates for the breeding of alfalfa strains with enhanced stress tolerance.PMID:38064475 | DOI:10.1371/journal.pone.0295592

Environ Sci Technol. 2023 Dec 8. doi: 10.1021/acs.est.3c04844. Online ahead of print.ABSTRACTPerfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are persistent environmental contaminants that are of increasing public concern worldwide. However, their relationship with colorectal cancer (CRC) is poorly understood. This study aims to comprehensively investigate the effect of PFOS and PFOA on the development and progression of CRC in vitro using a series of biological techniques and metabolic profiling. Herein, the migration of three-dimensional (3D) spheroids of two CRC cell lines, SW48 KRAS wide-type (WT) and SW48 KRAS G12A, were observed after exposure to PFOS and PFOA at 2 μM and 10 μM for 7 days. The time and dose-dependent migration phenotype induced by 10 μM PFOS and PFOA was further confirmed by wound healing and trans-well migration assays. To investigate the mechanism of action, derivatization-mass spectrometry-based metabolic profiles were examined from 3D spheroids of SW48 cell lines exposed to PFOS and PFOA (2 μM and 10 μM). Our findings revealed this exposure altered epithelial-mesenchymal transition related metabolic pathways, including fatty acid β-oxidation and synthesis of proteins, nucleotides, and lipids. Furthermore, this phenotype was confirmed by the downregulation of E-cadherin and upregulation of N-cadherin and vimentin. These findings show novel insight into the relationship between PFOS, PFOA, and CRC.PMID:38064429 | DOI:10.1021/acs.est.3c04844

J Agric Food Chem. 2023 Dec 8. doi: 10.1021/acs.jafc.3c06878. Online ahead of print.ABSTRACTTartary buckwheat is an annual minor cereal crop with a variety of secondary metabolites, endowing it with a high nutritional and medicinal value. Flavonoids constitute the primary compounds of Tartary buckwheat. Recently, metabolomics, as an adjunct breeding method, has been increasingly employed in crop research. This study explores the correlation between the total flavonoid content (TFC) and antioxidant capacity in 167 Tartary buckwheat varieties. Ten Tartary buckwheat varieties with significant differences in flavonoid content and antioxidant capacity were selected by cluster analysis. With the use of liquid chromatography-mass spectrometry, 58 flavonoid compounds were identified, namely, 42 flavonols, 10 flavanols, 3 flavanones, 1 isoflavone, 1 anthocyanidin, and 1 proanthocyanidin. Different samples were clearly separated by employing principal component analysis and partial least-squares discriminant analysis. Eight differential flavonoid compounds were further selected through volcano plots and variable importance in projection. Differential metabolites were highly correlated with TFC and antioxidant capacity. Finally, metabolic markers of kaempferol-3-O-hexoside, kaempferol-7-O-glucoside, and naringenin-O-hexoside were determined by the random forest model. The findings provide a basis for the selection and identification of Tartary buckwheat varieties with high flavonoid content and strong antioxidant activity.PMID:38063436 | DOI:10.1021/acs.jafc.3c06878