PubMed

Zhongguo Zhong Yao Za Zhi. 2022 Dec;47(24):6679-6686. doi: 10.19540/j.cnki.cjcmm.20220728.401.ABSTRACTNon-targeted metabonomics was used to investigate the metabolite changes in the glioblastoma orthotopic tumor-bearing mice after timosaponin AⅢ(TIA) intervention to explore the metabolic relevant mechanism of glioblastoma and TIA intervention. The mice were randomly divided into a blank group, a model group, and a TIA group. HPLC-LTQ-Orbitrap Elite liquid chromatography-mass spectrometry was used to detect the metabolite changes in the serum of rats in the three groups after treatment for 4 weeks. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed on the metabolites, and the differential metabolites were selected based on VIP values and P values(P<0.05). The results showed that TIA significantly inhibited the in vivo glioblastoma growth, but it had limited influence on body weight. Serum samples were clearly distinguishable among groups. As compared with the blank group, six metabolites including ceramide, succinic acid, α-ketoglutarate acid(αKG), citric acid, indophenol sulfate, and 3 a, 6 b, 7 b-trihydroxy-5 b-cholic acid in the model group significantly decreased. As compared with the model group, five metabolites except phenol sulfate, PC[20:4(5Z,7E,11Z,14Z)-OH(9)/diMe(9,3)], o-palmitoyl carnitine, α-ketoglutarate acid, and citric acid in the TIA group significantly increased. According to the MetaboAnalyst enrichment analysis, the metabolic pathways were enriched in the tricarboxylic acid cycle, and alanine, aspartic acid, and glutamate metabolism. These results show that during the glioblastoma growth process, the metabolites including αKG and citric acid are down-regulated, and TIA exerts the anti-glioblastoma growth effect through the regulation of tricarboxylic acid cycle, and alanine, aspartic acid, and glutamate metabolism to elevate the levels of αKG, citric acid, and other metabolites.PMID:36604918 | DOI:10.19540/j.cnki.cjcmm.20220728.401

Cancer Cell Int. 2023 Jan 5;23(1):2. doi: 10.1186/s12935-022-02845-y.ABSTRACTBACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. The molecules (proteins, metabolites) secreted by tumors affect their extracellular milieu to support cancer progression. If secreted in amounts detectable in plasma, these molecules can also serve as useful, minimal invasive biomarkers. The knowledge of ccRCC tumor microenvironment is fragmentary. In particular, the links between ccRCC transcriptome and the composition of extracellular milieu are weakly understood. In this study, we hypothesized that ccRCC transcriptome is reprogrammed to support alterations in tumor microenvironment. Therefore, we comprehensively analyzed ccRCC extracellular proteomes and metabolomes as well as transcriptomes of ccRCC cells to find molecules contributing to renal tumor microenvironment.METHODS: Proteomic and metabolomics analysis of conditioned media isolated from normal kidney cells as well as five ccRCC cell lines was performed using mass spectrometry, with the following ELISA validation. Transcriptomic analysis was done using microarray analysis and validated using real-time PCR. Independent transcriptomic and proteomic datasets of ccRCC tumors were used for the analysis of gene and protein expression as well as the level of the immune infiltration.RESULTS: Renal cancer secretome contained 85 proteins detectable in human plasma, consistently altered in all five tested ccRCC cell lines. The top upregulated extracellular proteins included SPARC, STC2, SERPINE1, TGFBI, while downregulated included transferrin and DPP7. The most affected extracellular metabolites were increased 4-hydroxy-proline, succinic acid, cysteine, lactic acid and downregulated glutamine. These changes were associated with altered expression of genes encoding the secreted proteins (SPARC, SERPINE1, STC2, DPP7), membrane transporters (SLC16A4, SLC6A20, ABCA12), and genes involved in protein trafficking and secretion (KIF20A, ANXA3, MIA2, PCSK5, SLC9A3R1, SYTL3, and WNTA7). Analogous expression changes were found in ccRCC tumors. The expression of SPARC predicted the infiltration of ccRCC tumors with endothelial cells. Analysis of the expression of the 85 secretome genes in > 12,000 tumors revealed that SPARC is a PanCancer indicator of cancer-associated fibroblasts' infiltration.CONCLUSIONS: Transcriptomic reprogramming of ccRCC supports the changes in an extracellular milieu which are associated with immune infiltration. The proteins identified in our study represent valuable cancer biomarkers detectable in plasma.PMID:36604669 | DOI:10.1186/s12935-022-02845-y

Nat Microbiol. 2023 Jan;8(1):91-106. doi: 10.1038/s41564-022-01279-6. Epub 2023 Jan 5.ABSTRACTSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a phlebovirus in the Bunyaviridae family. Infection can result in systemic inflammatory response syndrome with a high fatality rate, and there are currently no treatments or vaccines available. The microbiota has been implicated in host susceptibility to systemic viral infection and disease outcomes, but whether the gut microbiota is implicated in severe fever with thrombocytopenia syndrome virus (SFTSV) infection is unknown. Here, we analysed faecal and serum samples from patients with SFTS using 16S ribosomal RNA-sequencing and untargeted metabolomics, respectively. We found that the gut commensal Akkermansia muciniphila increased in relative abundance over the course of infection and was reduced in samples from deceased patients. Using germ-free or oral antibiotic-treated mice, we found that A. muciniphila produces the β-carboline alkaloid harmaline, which protects against SFTSV infection by suppressing NF-κB-mediated systemic inflammation. Harmaline indirectly modulated the virus-induced inflammatory response by specifically enhancing bile acid-CoA: amino acid N-acyltransferase expression in hepatic cells to increase conjugated primary bile acids, glycochenodeoxycholic acid and taurochenodeoxycholic acid. These bile acids induced transmembrane G-protein coupled receptor-5-dependent anti-inflammatory responses. These results indicate the probiotic potential of A. muciniphila in mitigating SFTSV infection.PMID:36604506 | DOI:10.1038/s41564-022-01279-6

Sci Rep. 2023 Jan 5;13(1):186. doi: 10.1038/s41598-022-26515-1.ABSTRACTPosition within the social group has consequences on individual lifespans in diverse taxa. This is especially obvious in eusocial insects, where workers differ in both the tasks they perform and their aging rates. However, in eusocial wasps, bees and ants, the performed task usually depends strongly on age. As such, untangling the effects of social role and age on worker physiology is a key step towards understanding the coevolution of sociality and aging. We performed an experimental protocol that allowed a separate analysis of these two factors using four groups of black garden ant (Lasius niger) workers: young foragers, old foragers, young nest workers, and old nest workers. We highlighted age-related differences in the proteome and metabolome of workers that were primarily related to worker subcaste and only secondarily to age. The relative abundance of proteins and metabolites suggests an improved xenobiotic detoxification, and a fuel metabolism based more on lipid use than carbohydrate use in young ants, regardless of their social role. Regardless of age, proteins related to the digestive function were more abundant in nest workers than in foragers. Old foragers were mostly characterized by weak abundances of molecules with an antibiotic activity or involved in chemical communication. Finally, our results suggest that even in tiny insects, extended lifespan may require to mitigate cancer risks. This is consistent with results found in eusocial rodents and thus opens up the discussion of shared mechanisms among distant taxa and the influence of sociality on life history traits such as longevity.PMID:36604491 | DOI:10.1038/s41598-022-26515-1

Sci Rep. 2023 Jan 5;13(1):203. doi: 10.1038/s41598-022-26816-5.ABSTRACTCrohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. A clear gap in our existing CD diagnostics and current disease management approaches is the lack of highly specific biomarkers that can be used to streamline or personalize disease management. Comprehensive profiling of metabolites holds promise; however, these high-dimensional profiles need to be reduced to have relevance in the context of CD. Machine learning approaches are optimally suited to bridge this gap in knowledge by contextualizing the metabolic alterations in CD using genome-scale metabolic network reconstructions. Our work presents a framework for studying altered metabolic reactions between patients with CD and controls using publicly available transcriptomic data and existing gene-driven metabolic network reconstructions. Additionally, we apply the same methods to patient-derived ileal enteroids to explore the utility of using this experimental in vitro platform for studying CD. Furthermore, we have piloted an untargeted metabolomics approach as a proof-of-concept validation strategy in human ileal mucosal tissue. These findings suggest that in silico metabolic modeling can potentially identify pathways of clinical relevance in CD, paving the way for the future discovery of novel diagnostic biomarkers and therapeutic targets.PMID:36604447 | DOI:10.1038/s41598-022-26816-5

Amino Acids. 2023 Jan 5. doi: 10.1007/s00726-022-03231-8. Online ahead of print.ABSTRACTDoxorubicin (DOX) is a cornerstone of chemotherapy for solid tumors and leukemias. DOX-induced cognitive impairment, termed chemo brain, has been reported in cancer survivors, whereas its mechanism remains poorly understood. Here we initially evaluated the cognitive impairments of mice treated with clinically relevant, long-term, low-dosage of DOX. Using HILIC-MS/MS-based targeted metabolomics, we presented the changes of 21 amino acids across six anatomical brain regions of mice with DOX-induced chemo brain. By mapping the altered amino acids to the human metabolic network, we constructed an amino acid-based network module for each brain region. We identified phenylalanine, tyrosine, methionine, and γ-aminobutyric acid as putative signatures of three regions (hippocampus, prefrontal cortex, and neocortex) highly associated with cognition. Relying on the reported mouse brain metabolome atlas, we found that DOX might perturb the amino acid homeostasis in multiple brain regions, similar to the changes in the aging brain. Correlation analysis suggested the possible indirect neurotoxicity of DOX that altered the brain levels of phenylalanine, tyrosine, and methionine by causing metabolic disorders in the liver and kidney. In summary, we revealed the region-specific amino acid signatures as actionable targets for DOX-induced chemo brain, which might provide safer treatment and improve the quality of life among cancer survivors.PMID:36604337 | DOI:10.1007/s00726-022-03231-8

Acta Biochim Biophys Sin (Shanghai). 2022 Nov 25;54(11):1599-1609. doi: 10.3724/abbs.2022162.ABSTRACTPancreatic neuroendocrine tumor (pNET) is the second most common malignant tumors of the pancreas. Multiple endocrine neoplasia 1 ( MEN1) is the most frequently mutated gene in pNETs and MEN1-encoded protein, menin, is a scaffold protein that interacts with transcription factors and chromatin-modifying proteins to regulate various signaling pathways. However, the role of MEN1 in lipid metabolism has not been studied in pNETs. In this study, we perform targeted metabolomics analysis and find that MEN1 promotes the generation and oxidation of polyunsaturated fat acids (PUFAs). Meanwhile lipid peroxidation is a hallmark of ferroptosis, and we confirm that MEN1 promotes ferroptosis by inhibiting the activation of mTOR signaling which is the central hub of metabolism. We show that stearoyl-coA desaturase (SCD1) is the downstream of MEN1-mTOR signaling and oleic acid (OA), a metabolite of SCD1, recues the lipid peroxidation caused by MEN1 overexpression. The negative correlation between MEN1 and SCD1 is further verified in clinical specimens. Furthermore, we find that BON-1 and QGP-1 cells with MEN1 overexpression are more sensitive to everolimus, a widely used drug in pNETs that targets mTOR signaling. In addition, combined use everolimus with ferroptosis inducer, RSL3, possesses a more powerful ability to kill cells, which may provide a new strategy for the comprehensive therapy of pNETs.PMID:36604142 | DOI:10.3724/abbs.2022162

Gut. 2023 Jan 5:gutjnl-2022-327756. doi: 10.1136/gutjnl-2022-327756. Online ahead of print.ABSTRACTOBJECTIVE: Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA.DESIGN: Microbiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensal Parabacteroides distasonis in RA. The effects of P. distasonis-derived microbial metabolites on the differentiation of CD4+ T cells and macrophage polarisation were also investigated.RESULTS: The relative abundance of P. distasonis in new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with live P. distasonis (LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth of P. distasonis.CONCLUSIONS: P. distasonis and ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.PMID:36604114 | DOI:10.1136/gutjnl-2022-327756

Carbohydr Polym. 2023 Feb 15;302:120395. doi: 10.1016/j.carbpol.2022.120395. Epub 2022 Nov 30.ABSTRACTIn cancer microenvironment, aberrant glycosylation events of ECM proteins and cell surface receptors occur. We developed a protocol to generate 3D bioprinted models of colorectal cancer (CRC) crosslinking hyaluronic acid and gelatin functionalized with three signalling glycans characterized in CRC, 3'-Sialylgalactose, 6'-Sialylgalactose and 2'-Fucosylgalactose. The crosslinking, performed exploiting azide functionalized gelatin and hyaluronic acid and 4arm-PEG-dibenzocyclooctyne, resulted in biocompatible hydrogels that were 3D bioprinted with commercial CRC cells HT-29 and patient derived CRC tumoroids. The glycosylated hydrogels showed good 3D printability, biocompatibility and stability over the time. SEM and synchrotron radiation SAXS/WAXS analysis revealed the influence of glycosylation in the construct morphology, whereas MALDI-MS imaging showed that protein profiles of tumoroid cells vary with glycosylation, indicating that sialylation and fucosylation of ECM proteins induce diverse alterations to the proteome of the tumoroid and surrounding cells.PMID:36604073 | DOI:10.1016/j.carbpol.2022.120395

J Ethnopharmacol. 2023 Jan 2:116116. doi: 10.1016/j.jep.2022.116116. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Hypertension coincides with the category of "vertigo" and/or "headache" on the basis clinical manifestations and traditional Chinese medicine (TCM) theory. Chai-Gui Decoction (CGD), which is in usage for relieving "vertigo" and/or "headache", had been demonstrated to be useful in ameliorating hypertension.AIM OF STUDY: This study was planned to investigate the mechanism of CGD and its components in hypertension by using spontaneous hypertension rat (SHR).MATERIALS AND METHODS: CGD extract and its classification component samples (compounds in plasma, CP; compounds in gut, CG; compounds in plasma and gut, CPG) were prepared for animal experiment. SHR rats were induced with CGD extract (3 g/kg/d BW, 5 g/kg/d BW, 15 g/kg/d BW) and CGD-component classes (CP = 19.501 mg/kg/d, CG = 5.240 mg/kg/d, CPG = 24.741 mg/kg/d) for 4 weeks. Blood pressure (BP) and indexes of renin-angiotensin-aldosterone system (RAAS system) were measured. Histopathology was carried out to assess the efficacy of CGD and its components on aorta tissues. Untargeted metabolomics of lipid from rat serum samples were applied by Ultra-High performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and chemometric analysis to explore the relationship between metabolic pathways and hypertension. 16S rRNA gene sequencing of rat colon content and bioinformatics analysis were used to characterize the effects of CGD and its components on the gut microbiota composition of SHR rats.RESULTS: CGD and its component mixtures showed antihypertensive effect on SHR rats, decreased the blood pressure and reduced the aortic wall thickness in SHR rats. CGD and its component mixtures could improve the RAAS in SHR rats, including increase the percentage of angiotensin 1-7 (Ang 1-7), decrease the percentage of angiotensin II (Ang II), and decrease the Ang Ⅱ/Ang 1-7 ratio. CGD and its component mixtures could regulate the metabolome in SHR rats, mainly as decreasing the higher serum levels of Lysophosphatidylcholine (LPC) 16: 0, LPC 20: 4, and LPC 22: 6. In addition, bacteria from family S24-7 were negatively correlated with levels of LPE 16:0, LPE 18:0, LPE 18:1, and LPE 18:2.CONCLUSION: CGD and its component mixtures exhibited antihypertensive effect on SHR rats. The underlying mechanism could be related to modulation on RAAS, LPC metabolism and the bacterial abundance of family S24-7 in gut.PMID:36603783 | DOI:10.1016/j.jep.2022.116116

Biochem Pharmacol. 2023 Jan 2:115405. doi: 10.1016/j.bcp.2022.115405. Online ahead of print.ABSTRACTMitochondria and mitochondrial proteins represent a group of promising pharmacological-target candidates in the search of new molecular targets and drugs to counteract the onset of hypertension and more in general cardiovascular diseases (CVDs). Indeed, several mitochondrial pathways result impaired in CVDs, showing ATP depletion and ROS production as common traits of cardiac tissue degeneration. Thus, targeting mitochondrial dysfunction in cardiomyocytes can represent a successful strategy to prevent heart failure. In this context, the identification of new pharmacological targets among mitochondrial proteins paves the way for the design of new selective drugs. Thanks to the advances in omics approaches, to a greater availability of mitochondrial crystallized protein structures and to the development of new computational approaches for protein 3D-modelling and drug-design, it is now possible to investigate in detail impaired mitochondrial pathways in CVDs. Furthermore, it is possible to design new powerful drugs able to hit the selected pharmacological targets in a highly selective way to rescue mitochondrial dysfunction and prevent cardiac tissue degeneration. The role of mitochondrial dysfunction in the onset of CVDs appears increasingly evident, as reflected by the impairment of proteins involved in lipid peroxidation, mitochondrial dynamics, respiratory chain complexes, and membrane polarization maintenance in CVD patients. Conversely, little is known about proteins responsible for the cross-talk between mitochondria and cytoplasm in cardiomyocytes. Mitochondrial transporters of the SLC25A family, in particular, are responsible for the translocation of nucleotides (e.g., ATP), amino acids (e.g., aspartate, glutamate, ornithine), organic acids (e.g. malate and 2-oxoglutarate), and other cofactors (e.g., inorganic phosphate, NAD+, FAD, carnitine, CoA derivatives) between the mitochondrial and cytosolic compartments. Thus, mitochondrial transporters play a key role in the mitochondria-cytosol cross-talk by leading metabolic pathways such as the malate/aspartate shuttle, the carnitine shuttle, the ATP export from mitochondria, and the regulation of permeability transition pore opening. Since all these pathways are crucial for maintaining healthy cardiomyocytes, mitochondrial carriers emerge as an interesting class of new possible pharmacological targets for CVD treatments.PMID:36603686 | DOI:10.1016/j.bcp.2022.115405

Sci Total Environ. 2023 Jan 2:161247. doi: 10.1016/j.scitotenv.2022.161247. Online ahead of print.ABSTRACTPolystyrene nanoplastics (PSNPs, <100nm), an artificial pollutant that is widespread in the environment, can be assimilated by plants to alter plant gene expression and its metabolic pathway; thus, interfering with physiological homeostasis and growth of plants. Recently, the biosafety and potential environmental risks of PSNPs have attracted enormous attention. However, the knowledge regarding the uptake and phytotoxicity of atmosphere PSNPs subsiding to plant leaves is still limited. Here, we separately applied 50 mg/L and 100 mg/L PSNPs on cucumber leaves to simulate the plant response to the atmosphere PSNPs. We found that the PSNPs can be accumulated on the surface of cucumber leaves and are also able to be uptake by cucumber leaf stomata. The repertoires of metabolomics and transcriptomics from cucumber leaves upon PSNPs treatment demonstrated that the deposition of PSNPs on leaves alters the biosynthesis of various metabolites and the expression of a variety of genes. The leaves exposure to low concentration (50 mg/L) of PSNPs impact the genes involved in carbohydrate metabolism and the biosynthesis of metabolites related to membrane stability maintenance, thereby, probably enhancing plant tolerance to the stress caused by PSNPs. Whereas, exposure to high concentration (100 mg/L) of PSNPs, both nitrogen and carbohydrate metabolism in cucumber leaves are affected, as well as that the photosynthetic capacity was decreased, leading to the threat to plant health. Combined omics technologies, our findings advance our understanding about how the PSNPs released to ecological environment influence the terrestrial plant growth and provide phytotoxic mechanism.PMID:36603646 | DOI:10.1016/j.scitotenv.2022.161247

Sci Total Environ. 2023 Jan 2:161330. doi: 10.1016/j.scitotenv.2022.161330. Online ahead of print.ABSTRACTIn order to understand the mechanism that allows modified biochar (BC) to enhance the salt tolerance and growth of crops in saline-alkali soil, we tested the effects of ordinary BC, nanoparticle-size BC, acidified BC (HBC), and acidified nanoparticle-size BC on winter wheat growth and the soil properties by combining microbiological and metabolomics analyses. The results showed that compared with the control with no BC, the plant height increased by 17.33 % under HBC and the proportion of large soil aggregates increased by 1.25-2.83 times. HBC increased the relative abundances of some dominant genera of bacteria (e.g., Streptococcus) and fungi (e.g., Mycothermus), as well as functions such as bacterial metabolic genetic information processing and cellular processes, and reduced the abundance of pathotrophic fungi. Metabolomics analysis showed that HBC upregulated various metabolites (including amino acids and their derivatives, lipids, flavonoids, and organic acids) and five main metabolic pathways. Among the KEGG pathways, the pyrimidine metabolism pathway was significantly upregulated, as well as crop leaf metabolism, β-alanine metabolism, and valine, leucine, and isoleucine metabolism, and the antioxidant levels and resistance to salt-alkali stress were enhanced in winter wheat leaves. Partial least squares-path modeling suggested that HBC affected the growth of winter wheat by significantly changing the soil physicochemical properties and microbial structure (path coefficients of 0.566 and 0.512, respectively).PMID:36603639 | DOI:10.1016/j.scitotenv.2022.161330

Biochem Biophys Res Commun. 2022 Dec 28;643:129-138. doi: 10.1016/j.bbrc.2022.12.078. Online ahead of print.ABSTRACTThere is an alarming increase in incidence of fatty liver disease worldwide. The fatty liver disease spectrum disease ranges from simple steatosis (NAFL) to steatohepatitis (NASH) which culminates in cirrhosis and cancer. Altered metabolism is a hallmark feature associated with fatty liver disease and palmitic acid is the most abundant saturated fatty acid, therefore, the aim of this study was to compare metabolic profiles altered in hepatocytes treated with palmitic acid and also the differentially expressed plasma metabolites in spectrum of nonalcoholic fatty liver. The metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS) platform. Hepatocyte cell lines PH5CH8 and HepG2 cells when treated with 400 μM dose of palmitic acid showed typical features of steatosis. Metabolomic analysis of lipid treated hepatocyte cell lines showed differential changes in phenylalanine and tyrosine pathways, fatty acid metabolism and bile acids. The key metabolites tryptophan, kynurenine and carnitine differed significantly between subjects with NAFL, NASH and those with cirrhosis. As the tryptophan-kynurenine axis is also involved in denovo synthesis of NAD+, we found significant alterations in the NAD+ related metabolites in both palmitic acid treated and also fatty liver disease with cirrhosis. The study underscores the importance of amino acid and NAD+supplementation as promising strategies in fatty liver disorder.PMID:36603530 | DOI:10.1016/j.bbrc.2022.12.078

Food Chem. 2022 Dec 23;409:135295. doi: 10.1016/j.foodchem.2022.135295. Online ahead of print.ABSTRACTThe current consumers' demand for food naturalness is urging the search for new functional foods of natural origin with enhanced health-promoting properties. In this sense, algae constitute an underexplored biological source of nutraceuticals that can be used to fortify food products. Both marine macroalgae (or seaweeds) and microalgae exhibit a myriad of chemical constituents with associated features as a result of their primary and secondary metabolism. Thus, primary metabolites, especially polysaccharides and phycobiliproteins, present interesting properties to improve the rheological and nutritional properties of food matrices, whereas secondary metabolites, such as polyphenols and xanthophylls, may provide interesting bioactivities, including antioxidant or cytotoxic effects. Due to the interest in algae as a source of nutraceuticals by the food and related industries, novel strategies should be undertaken to add value to their derived functional components. As a result, metabolomics is considered a high throughput technology to get insight into the full metabolic profile of biological samples, and it opens a wide perspective in the study of algae metabolism, whose knowledge is still little explored. This review focuses on algae metabolism and its applications in the food industry, paying attention to the promising metabolomic approaches to be developed aiming at the functional characterization of these organisms.PMID:36603477 | DOI:10.1016/j.foodchem.2022.135295

Vet Parasitol. 2022 Dec 23;314:109868. doi: 10.1016/j.vetpar.2022.109868. Online ahead of print.ABSTRACTEncystation in Cryptocaryon irritans is a fundamental process for environmental resistance and development. Autophagy participates in the encystation of ciliates, and rapamycin can induce autophagy in the cells. A set of genes and metabolites related to autophagy and encystation are highly elaborative. The existence of these genes and metabolites and their role are well characterized. However, little is known about their role in protozoans such as ciliates. The newly produced C. irritans protomonts were exposed to an optimal concentration of rapamycin (1400 nM), and the survival, encystation, microstructure/ultrastructure, transcriptomic and metabolomic profile in treated and control protomonts were investigated. The results showed that exposure of protomonts to rapamycin at 4 h significantly lowered the survival and encystation rates to 91.62 % and 98.44 % compared to the control group (100 %, p ≤ 0.05). Morphological alterations observed in light microscopy and transmission electron microscopy (TEM) demonstrated that the drug significantly changed cell symmetry by causing the formation of various autophagic vacuoles/vesicles. The transcriptome sequencing of rapamycin-treated protomont revealed that 2249 (1837 up-regulated and 977 down-regulated) differentially expressed genes (DEGs) were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 226 DEGs were successfully annotated in 21 pathways (p˂0.05), including most enriched pathways apoptosis and phagosome with 25 and 24 DEGs, respectively. Most unigenes were assigned to autophagy-related pathways; 24 DEGs were classified into phagosomes, and 15 DEGs were assigned to lysosome pathways. Cytoskeleton and cell progression-associated genes were down-regulated. Besides, cell death-inducing proteins were up-regulated. The metabolomic analysis revealed exposure to rapamycin treatment enhanced protomont metabolites, including L-Cysteine, which is related to autophagy. Rapamycin had influenced the gene and metabolites of protomont; activating autophagy with inhibition of mechanistic target of rapamycin, (mTOR). The process negatively influences protomont morphology, encystation, and survival. Further autophagy-related gene silencing can be investigated via genome sequencing of C. irritans to study encystation.PMID:36603452 | DOI:10.1016/j.vetpar.2022.109868

Front Med. 2023 Jan 5. doi: 10.1007/s11684-022-0943-0. Online ahead of print.ABSTRACTKetone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.PMID:36602721 | DOI:10.1007/s11684-022-0943-0

Arch Microbiol. 2023 Jan 5;205(1):54. doi: 10.1007/s00203-022-03391-x.ABSTRACTThe ocean is a treasure trove of both living and nonliving creatures, harboring incredibly diverse group of organisms. A plethora of marine sourced bioactive compounds are discovered over the past few decades, many of which are found to show antibiofilm activity. These are of immense clinical significance since the formation of microbial biofilm is associated with the development of high antibiotic resistance. Biofilms are also responsible to bring about problems associated with industries. In fact, the toilets and wash-basins also show degradation due to development of biofilm on their surfaces. Antimicrobial resistance exhibited by the biofilm can be a potent threat not only for the health care unit along with industries and daily utilities. Various recent studies have shown that the marine members of various kingdom are capable of producing antibiofilm compounds. Many such compounds are with unique structural features and metabolomics approaches are essential to study such large sets of metabolites. Associating holobiome metabolomics with analysis of their chemical attribute may bring new insights on their antibiofilm effect and their applicability as a substitute for conventional antibiotics. The application of computer-aided drug design/discovery (CADD) techniques including neural network approaches and structured-based virtual screening, ligand-based virtual screening in combination with experimental validation techniques may help in the identification of these molecules and evaluation of their drug like properties.PMID:36602609 | DOI:10.1007/s00203-022-03391-x

Arch Toxicol. 2023 Jan 5. doi: 10.1007/s00204-022-03431-x. Online ahead of print.ABSTRACTDeoxynivalenol (DON) is widely emerging in various grain crops, milk, and wine products, which can trigger different toxic effects on humans and animals by inhalation or ingestion. It also imposes a considerable financial loss on the agriculture and food industry each year. Previous studies have reported acute and chronic toxicity of DON in liver, and liver is not only the main detoxification organ for DON but also the circadian clock oscillator directly or indirectly regulates critical physiologically hepatic functions under different physiological and pathological conditions. However, researches on the association of circadian rhythm in DON-induced liver damage are limited. In the present study, mice were divided into four groups (CON, DON, Bmal1OE, and Bmal1OE + DON) and AAV8 was used to activate (Bmal1) expression in liver. Then mice were gavaged with 5 mg/kg bw/day DON or saline at different time points (ZT24 = 0, 4, 8, 12, 16, and 20 h) in 1 day and were sacrificed 30 min after oral gavage. The inflammatory cytokines, signal transducers, and activators of transcription Janus kinase/signal transducers and activator of transcription 3 (JAKs/STAT3) pathway and bile acids levels were detected by enzyme-linked immunosorbent assay (ELISA), western blotting, and target metabolomics, respectively. The DON group showed significantly elevated interleukin-1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels (P < 0.05 for both) and impaired liver function with rhythm disturbances compared to the CON and Bmal1OE groups. At the molecular level, expressions of some circadian clock proteins were significantly downregulated (P < 0.05 for both) and JAKs/STAT3 pathway was activated during DON exposure, accompanied by indicated circadian rhythm disturbance and inflammatory damage. Importantly, Bmal1 overexpression attenuated DON-induced liver damage, while related hepatic bile acids such as cholic acid (CA) showed a decreasing trend in the DON group compared with the CON group. Our study demonstrates a novel finding that Bmal1 plays a critical role in attenuating liver damage by inhibiting inflammatory levels and maintaining bile acids levels under the DON condition. Therefore, Bmal1 may also be a potential molecular target for reducing the hepatotoxic effects of DON in future studies.PMID:36602574 | DOI:10.1007/s00204-022-03431-x

Anal Bioanal Chem. 2023 Jan 5. doi: 10.1007/s00216-022-04492-8. Online ahead of print.ABSTRACTQuality control of Radix Bupleuri (RB) can be challenging due to the complexity of origin, the similar morphological characteristics, and the diversity of the multiple components. In this study, an integrated strategy for extensive identification of metabolites in plants based on multiple data processing methods was proposed to distinguish four commercially available RB species. First, the pre-processed mass spectrometry data was uploaded to Global Natural Products Social Molecular Networking (GNPS) for spectral library search and molecular network analysis, which can effectively differentiate isomers and reduce molecular redundancy. Second, the possible cleavage mode was summarized from the characteristic MS/MS fragment ions of saikoside standard, and then the possible structure of saikoside in the sample was deduced according to the cleavage patterns. Third, collected all kinds of RB components reported in the literature and matched the information in the samples to obtain more comprehensive information about metabolites. Finally, chemical markers were found employing chemometrics. This strategy not only increases the variety and number of identified components, but also improves the accuracy of the data. Based on this strategy, a total of 132 components were identified from different species of RB, and 14 chemical constituents were considered to be potential chemical markers to distinguish four kinds of RB. Among them, saikogenin a, hydroxy-saikosaponin a, hydroxy-saikosaponin d, and rutinum were of great significance for identification. The method proposed in this study not only successfully identified and distinguished four species of RB, but also laid a good theoretical foundation for regulating the RB market. This strategy provides promising perspectives in the accurate analysis of the ingredients of traditional Chinese medicine.PMID:36602568 | DOI:10.1007/s00216-022-04492-8