PubMed

Nucleic Acids Res. 2022 Nov 24:gkac1083. doi: 10.1093/nar/gkac1083. Online ahead of print.ABSTRACTThe Bioinformation and DNA Data Bank of Japan (DDBJ) Center (https://www.ddbj.nig.ac.jp) maintains database archives that cover a wide range of fields in life sciences. As a founding member of the International Nucleotide Sequence Database Collaboration (INSDC), our primary mission is to collect and distribute nucleotide sequence data, as well as their study and sample information, in collaboration with the National Center for Biotechnology Information in the United States and the European Bioinformatics Institute. In addition to INSDC resources, the Center operates databases for functional genomics (GEA: Genomic Expression Archive), metabolomics (MetaboBank), and human genetic and phenotypic data (JGA: Japanese Genotype-Phenotype Archive). These databases are built on the supercomputer of the National Institute of Genetics, whose remaining computational capacity is actively utilized by domestic researchers for large-scale biological data analyses. Here, we report our recent updates and the activities of our services.PMID:36420889 | DOI:10.1093/nar/gkac1083

Crit Rev Clin Lab Sci. 2022 Nov 24:1-18. doi: 10.1080/10408363.2022.2140329. Online ahead of print.ABSTRACTThe two common progressive lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are the leading causes of morbidity and mortality worldwide. Asthma-COPD overlap, referred to as ACO, is another complex pulmonary disease that manifests itself with features of both asthma and COPD. The disease has no clear diagnostic or therapeutic guidelines, thereby making both diagnosis and treatment challenging. Though a number of studies on ACO have been documented, gaps in knowledge regarding the pathophysiologic mechanism of this disorder exist. Addressing this issue is an urgent need for improved diagnostic and therapeutic management of the disease. Metabolomics, an increasingly popular technique, reveals the pathogenesis of complex diseases and holds promise in biomarker discovery. This comprehensive narrative review, comprising 99 original research articles in the last five years (2017-2022), summarizes the scientific advances in terms of metabolic alterations in patients with asthma, COPD, and ACO. The analytical tools, nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), commonly used to study the expression of the metabolome, are discussed. Challenges frequently encountered during metabolite identification and quality assessment are highlighted. Bridging the gap between phenotype and metabotype is envisioned in the future.PMID:36420874 | DOI:10.1080/10408363.2022.2140329

Comput Struct Biotechnol J. 2022 Nov 8;20:6149-6162. doi: 10.1016/j.csbj.2022.11.008. eCollection 2022.ABSTRACTThe etiology of neuropsychiatric disorders involves complex biological processes at different omics layers, such as genomics, transcriptomics, epigenetics, proteomics, and metabolomics. The advent of high-throughput technology, as well as the availability of large open-source datasets, has ushered in a new era in system biology, necessitating the integration of various types of omics data. The complexity of biological mechanisms, the limitations of integrative strategies, and the heterogeneity of multi-omics data have all presented significant challenges to computational scientists. In comparison to early and late integration, intermediate integration may transform each data type into appropriate intermediate representations using various data transformation techniques, allowing it to capture more complementary information contained in each omics and highlight new interactions across omics layers. Here, we reviewed multi-modal intermediate integrative techniques based on component analysis, matrix factorization, similarity network, multiple kernel learning, Bayesian network, artificial neural networks, and graph transformation, as well as their applications in neuropsychiatric domains. We depicted advancements in these approaches and compared the strengths and weaknesses of each method examined. We believe that our findings will aid researchers in their understanding of the transformation and integration of multi-omics data in neuropsychiatric disorders.PMID:36420153 | PMC:PMC9674886 | DOI:10.1016/j.csbj.2022.11.008

Comput Struct Biotechnol J. 2022 Nov 7;20:6067-6077. doi: 10.1016/j.csbj.2022.10.041. eCollection 2022.ABSTRACTThere is a dearth of studies focused on understanding pharmacokinetics, pharmacodynamics and toxicodynamics of polymyxins following direct administration to the central nervous system (CNS). In this study, for the first time, untargeted metabolomics were employed to ascertain the perturbations of brain metabolism in the rat cerebral cortex following direct brain injection of 0.75 mg/kg polymyxin B (1 and 4 h) through the right lateral ventricle. In the right cortex metabolome, ICV polymyxin B induced a greater perturbation at 1 h compared to negligible effect at 4 h. Pathway enrichment analysis showed that sphingolipid, arginine, and histidine metabolism, together with aminoacyl-tRNA biosynthesis were significantly affected in the right cortex metabolome. Furthermore, intracerebroventricular (ICV) polymyxin B dysregulated the two arms (CDP-choline and CDP-ethanolamine) of the Kennedy pathway that governs the de novo biosynthesis of neuronal phospholipids. Importantly, the key intermediates of metabolic pathways that maintain cellular redox balance (e.g., glutathione metabolism) and mitochondrial function (e.g., electron transport chain) were markedly depleted. The abundance of key metabolites (e.g., N-acetyl-l-glutamate) associated with diverse CNS disorders (e.g., neurodegenerative disease) were also significantly perturbed. The biological significance of these metabolic perturbations on the CNS includes impaired oxidant-antioxidant balance, impaired neuronal lipid homeostasis and mitochondrial dysfunction. Furthermore, ICV polymyxin B caused a significant alteration in the abundance of several metabolic biomarkers associated with cerebral ischemia, oxidative stress as well as certain neurological disorders. These findings may facilitate the development of new pharmacokinetic/pharmacodynamic strategies to attenuate polymyxins ICV related CNS toxicities and stimulate the discovery of safer next-generation polymyxin-like lipopeptide antibiotics.PMID:36420146 | PMC:PMC9667150 | DOI:10.1016/j.csbj.2022.10.041

PeerJ. 2022 Nov 18;10:e14404. doi: 10.7717/peerj.14404. eCollection 2022.ABSTRACTBACKGROUND: The banana-growing rhizosphere soil ecosystem is very complex and consists of an entangled network of interactions between banana plants, microbes and soil, so identifying key components in banana production is difficult. Most of the previous studies on these interactions ignore the role of the banana plant. At present, there is no research on the the micro-ecological environment of the banana planting growth cycle.METHODS: Based on high-throughput sequencing technology and metabolomics technology, this study analyzed the rhizosphere soil microbial community and metabolic dynamics of healthy banana plants during one growth cycle.RESULTS: Assessing the microbial community composition of healthy banana rhizosphere soil, we found that the bacteria with the highest levels were Proteobacteria, Chloroflexi, and Acidobacteria, and the dominant fungi were Ascomycota, Basidiomycota, and Mortierellomycota. The metabolite profile of healthy banana rhizosphere soil showed that sugars, lipids and organic acids were the most abundant, accounting for about 50% of the total metabolites. The correlation network between fungi and metabolites was more complex than that of bacteria and metabolites. In a soil environment with acidic pH, bacterial genera showed a significant negative correlation with pH value, while fungal genera showed no significant negative correlation with pH value. The network interactions between bacteria, between fungi, and between bacteria and fungi were all positively correlated.CONCLUSIONS: Healthy banana rhizosphere soil not only has a stable micro-ecology, but also has stable metabolic characteristics. The microorganisms in healthy banana rhizosphere soil have mutually beneficial rather than competitive relationships.PMID:36420134 | PMC:PMC9677880 | DOI:10.7717/peerj.14404

Front Plant Sci. 2022 Nov 7;13:1005711. doi: 10.3389/fpls.2022.1005711. eCollection 2022.ABSTRACTAngelica sinensis is a medicinal plant widely used to treat multiple diseases in Asia and Europe, which contains numerous active components with therapeutic value. The interaction between root and rhizosphere microorganisms is crucial for the growth and quality formation of medicinal plants. But the micro-plant-metabolite regulation patterns for A. sinensis remain largely undetermined. Here, we collected roots and rhizosphere soils from A. sinensis in seedling stage (M) and picking stage (G), respectively cultivated for one year and two years, generated metabolite for roots, microbiota data for rhizospheres, and conducted a comprehensive analysis. Changes in metabolic and microbial communities of A.sinensis over growth were distinct. The composition of rhizosphere microbes in G was dominated by proteobacteria, which had a strong correlation with the synthesis of organic acids, while in M was dominated by Actinobacteria, which had a strong correlation with the synthesis of phthalide and other organoheterocyclic compounds, flavonoids, amines, and fatty acid. Additionally, co-occurrence network analysis identified that Arthrobacter was found to be strongly correlated with the accumulation of senkyunolide A and n-butylidenephthalide. JGI 0001001.H03 was found to be strongly correlated with the accumulation of chlorogenic acid. Based on rhizosphere microorganisms, this study investigated the correlation between root metabolism and rhizosphere microbiota of A. sinensis at different growth stages in traditional geoherb region, which could provide references for exploring the quality formation mechanism of A. sinensis in the future.PMID:36420035 | PMC:PMC9676459 | DOI:10.3389/fpls.2022.1005711

iScience. 2022 Nov 4;25(12):105508. doi: 10.1016/j.isci.2022.105508. eCollection 2022 Dec 22.ABSTRACTAdenomyosis is a burdensome gynecologic condition that is associated with pelvic pain, dysmenorrhea, and abnormal uterine bleeding, leading to a negative impact on quality of life; and yet is often left undiagnosed. We recruited 108 women undergoing hysterectomy for benign gynecologic conditions and collected non-invasive cervicovaginal lavage samples for immunometabolic profiling. Patients were grouped according to adenomyosis status. We investigated the levels of 72 soluble immune proteins and >900 metabolites using multiplex immunoassays and an untargeted global metabolomics platform. There were statistically significant alterations in the levels of several immune proteins and a large quantity of metabolites, particularly cytokines related to type II immunity and amino acids, respectively. Enrichment analysis revealed that pyrimidine metabolism, carnitine synthesis, and histidine/histamine metabolism were significantly upregulated pathways in adenomyosis. This study demonstrates utility of non-invasive sampling combined with immunometabolic profiling for adenomyosis detection and a greater pathophysiological understanding of this enigmatic condition.PMID:36419846 | PMC:PMC9676393 | DOI:10.1016/j.isci.2022.105508

Front Cardiovasc Med. 2022 Nov 7;9:1019598. doi: 10.3389/fcvm.2022.1019598. eCollection 2022.ABSTRACTOBJECTIVES: Most patients with acute aortic dissection (AAD) have a history of hypertension. Diagnosis of AAD in patients with hypertension at an early stage is complicated and challenging. This study aimed to explore the distinctive metabolic changes in plasma samples of AAD patients with hypertension and patients with hypertension only and provide early identification and diagnosis of AAD in patients with hypertension.MATERIALS AND METHODS: We collected blood samples from 20 patients with type A AAD and hypertension admitted to the emergency department and physically examined other 20 patients with hypertension as controls. The plasma metabolomic profiles of these patients were determined using untargeted metabolomics with ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.RESULTS: A total of 38 metabolites that differed between the AAD and hypertension groups were screened. In the positive ion mode, 12 metabolites were different between the two groups, and in the negative ion mode, 26 metabolites were different. Among the 26 different metabolites detected by the negative ion mode, 21 were significantly upregulated and five were downregulated in patients with AAD compared to patients with hypertension. Moreover, five metabolites were upregulated and seven were significantly downregulated in patients with AAD compared to those with hypertension, as detected by the positive ion mode. The metabolites differentially expressed in AAD were mainly involved in lipid metabolism (fatty acid biosynthesis, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism), carbohydrate metabolism (galactose, fructose, and mannose metabolisms), and membrane transport (ATP-binding cassette transporters). Interestingly, plasma hydrocortisone and dimethylglycine concentrations were significantly increased in patients with type A AAD, with the highest area under the curve value (AUC = 0.9325 or 0.9200, respectively) tested by the receiver operating characteristic curve analysis.CONCLUSION: This study provides possible metabolic markers for the early clinical diagnosis of AAD in patients with hypertension.PMID:36419495 | PMC:PMC9676262 | DOI:10.3389/fcvm.2022.1019598

Front Cardiovasc Med. 2022 Nov 7;9:1033457. doi: 10.3389/fcvm.2022.1033457. eCollection 2022.ABSTRACTAIMS: PERM1 is a striated muscle-specific regulator of mitochondrial bioenergetics. We previously demonstrated that PERM1 is downregulated in the failing heart and that PERM1 positively regulates metabolic genes known as targets of the transcription factor ERRα and its coactivator PGC-1α in cultured cardiomyocytes. The aims of this study were to determine the effect of loss of PERM1 on cardiac function and energetics using newly generated Perm1-knockout (Perm1 -/-) mice and to investigate the molecular mechanisms of its transcriptional control.METHODS AND RESULTS: Echocardiography showed that ejection fraction and fractional shortening were lower in Perm1 -/- mice than in wild-type mice (both p < 0.05), and the phosphocreatine-to-ATP ratio was decreased in Perm1 -/- hearts (p < 0.05), indicating reduced contractile function and energy reserves of the heart. Integrated proteomic and metabolomic analyses revealed downregulation of oxidative phosphorylation and upregulation of glycolysis and polyol pathways in Perm1 -/- hearts. To examine whether PERM1 regulates energy metabolism through ERRα, we performed co-immunoprecipitation assays, which showed that PERM1 bound to ERRα in cardiomyocytes and the mouse heart. DNA binding and reporter gene assays showed that PERM1 was localized to and activated the ERR target promoters partially through ERRα. Mass spectrometry-based screening in cardiomyocytes identified BAG6 and KANK2 as potential PERM1's binding partners in transcriptional regulation. Mammalian one-hybrid assay, in which PERM1 was fused to Gal4 DNA binding domain, showed that the recruitment of PERM1 to a gene promoter was sufficient to activate transcription, which was blunted by silencing of either PGC-1α, BAG6, or KANK2.CONCLUSION: This study demonstrates that PERM1 is an essential regulator of cardiac energetics and function and that PERM1 is a novel transcriptional coactivator in the ERRα/PGC-1α axis that functionally interacts with BAG6 and KANK2.PMID:36419485 | PMC:PMC9676655 | DOI:10.3389/fcvm.2022.1033457

Front Microbiol. 2022 Nov 7;13:1053330. doi: 10.3389/fmicb.2022.1053330. eCollection 2022.ABSTRACTThe metabolic microenvironment of bacteria impacts drug efficacy. However, the metabolic mechanisms of drug-resistant Salmonella spp. remain largely unknown. This study characterized the metabolic mechanism of gentamicin-resistant Salmonella Choleraesuis and found that D-ribose increased the gentamicin-mediated killing of this bacteria. Non-targeted metabolomics of homologous gentamicin-susceptible Salmonella Choleraesuis (SCH-S) and gentamicin-resistant S. Choleraesuis (SCH-R) was performed using UHPLC-Q-TOF MS. The metabolic signature of SCH-R included disrupted central carbon metabolism and energy metabolism, along with dysregulated amino acid and nucleotide metabolism, vitamin and cofactor metabolism, and fatty acid synthesis. D-ribose, the most suppressed metabolite in SCH-R, was shown to strengthen gentamicin efficacy against SCH-R and a clinically isolated multidrug-resistant strain. This metabolite had a similar impact on Salmonella. Derby and Salmonella. Typhimurium. D-ribose activates central carbon metabolism including glycolysis, the pentose phosphate pathway (PPP), and the tricarboxylic acid cycle (TCA cycle), increases the abundance of NADH, polarizes the electron transport chain (ETC), and elevates the proton motive force (PMF) of cells, and induces drug uptake and cell death. These findings suggest that central carbon metabolism plays a critical role in the acquisition of gentamicin resistance by Salmonella, and that D-ribose may serve as an antibiotic adjuvant for gentamicin treatment of resistant bacterial infections.PMID:36419438 | PMC:PMC9676500 | DOI:10.3389/fmicb.2022.1053330

Front Microbiol. 2022 Nov 7;13:1017092. doi: 10.3389/fmicb.2022.1017092. eCollection 2022.ABSTRACTHorizontal gene transfer plays an important role in the spread of antibiotic resistance, in which plasmid-mediated conjugation transfer is the most important mechanism. While sub-minimal inhibitory concentrations (sub-MIC) of antibiotics could promote conjugation frequency, the mechanism by which sub-MIC levels of antibiotics affect conjugation frequency is not clear. Here, we used Klebsiella pneumoniae SW1780 carrying the multi-drug resistance plasmid pSW1780-KPC as the donor strain, to investigate the effects of sub-MICs of meropenem (MEM), ciprofloxacin (CIP), cefotaxime (CTX), and amikacin (AK) on conjugational transfer of pSW1780-KPC from SW1780 to Escherichia coli J53. Our results showed that the transfer frequencies increased significantly by treating SW1780 strain with sub-MIC levels of MEM, CIP, CTX and AK. Transfer frequencies at sub-MIC conditions in a Galleria mellonella were significantly higher than in vitro. To investigate gene expression and metabolic effects, RT-qPCR and LC-MS-based metabolome sequencing were performed. Transcript levels of T4SS genes virB1, virB2, virB4, virB8, and conjugation-related genes traB, traK, traE, and traL were significantly upregulated by exposure to sub-MICs of MEM, CIP, CTX, and AK. Metabolome sequencing revealed nine differentially regulated metabolites. Our findings are an early warning for a wide assessment of the roles of sub-MIC levels of antibiotics in the spread of antibiotic resistance.PMID:36419429 | PMC:PMC9678054 | DOI:10.3389/fmicb.2022.1017092

Front Microbiol. 2022 Nov 7;13:1028913. doi: 10.3389/fmicb.2022.1028913. eCollection 2022.ABSTRACTNeurocognitive disorders (NCDs) include complex and multifactorial diseases that affect many patients. The 5-hydroxytryptamine (5-HT) neuron system plays an important role in NCDs. Existing studies have reported that para-chlorophenylalanine (PCPA), a 5-HT scavenger, has a negative effect on cognitive function. However, we believe that PCPA may result in NCDs through other pathways. To explore this possibility, behavioral tests were performed to evaluate the cognitive function of PCPA-treated mice, suggesting the appearance of cognitive dysfunction and depression-like behavior. Furthermore, 16S rRNA and metabolomic analyses revealed that dysbiosis and acetate alternation could be related to PCPA-induced NCDs. Our results suggest that not only 5-HT depletion but also dysbiosis and acetate alternation contributed to PCPA-related NCDs. Specifically, the latter promotes NCDs by reducing short-chain fatty acid levels. Together, these findings provide an alternative perspective on PCPA-induced NCDs.PMID:36419424 | PMC:PMC9676499 | DOI:10.3389/fmicb.2022.1028913

Front Microbiol. 2022 Nov 7;13:1000033. doi: 10.3389/fmicb.2022.1000033. eCollection 2022.ABSTRACTEndophytic nitrogen-fixing bacteria are versatile and widely distributed in plants. Numerous strains of endophytic nitrogen-fixing bacteria are used as biofertilizers to minimize the utilization of chemical fertilizers, improve nutrient use efficiency, increase crop productivity, and reduce environmental pollution. However, the mechanism underlying the interaction between nitrogen-fixing bacteria and plants is still unclear. So, the present study was planned to assess the effects of endophytic nitrogen-fixing bacteria on sugarcane by analyzing the changes in physiological and biochemical activities. In the current study, Klebsiella variicola DX120E, an endophytic nitrogen-fixing bacterium, was inoculated on sugarcane varieties B8 and ROC22 to evaluate the effects on nitrogen and carbon metabolism-related enzymatic activity and biomass. Results showed that DX120E inoculation improved the enzymatic activities related to gluconeogenesis and nitrogen metabolism increased the sugarcane plant's height, cane juice Brix, biomass, chlorophyll, and soluble sugar content in sugarcane. Metabolomics analysis revealed that the metabolome modules were highly enriched in carbon and nitrogen metabolic pathways of strain-affected sugarcane than uninoculated control. The identified carbohydrates were associated with the glycolysis or gluconeogenesis and tricarboxylic acid (TCA) cycle in plants. Metabolomic profiling in the present investigation showed that carbohydrate metabolism is coordinated with nitrogen metabolism to provide carbon skeletons and energy to amino acid synthesis, and amino acid degradation results in several metabolites used by the citric acid cycle as an energy source. Moreover, differentially expressed metabolites of non-proteinogenic amino acids have a further complementary role to the action of endophytic nitrogen-fixing bacteria. Meanwhile, a significant difference in metabolites and metabolic pathways present in stems and leaves of B8 and ROC22 varieties was found. This study discovered the potential benefits of DX120E in sugarcane and suggested candidate regulatory elements to enhance interactions between nitrogen-fixing microbes and sugarcane.PMID:36419423 | PMC:PMC9678049 | DOI:10.3389/fmicb.2022.1000033

Front Microbiol. 2022 Nov 7;13:1046388. doi: 10.3389/fmicb.2022.1046388. eCollection 2022.ABSTRACTProkaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes) systems provide immunity against invading genetic elements such as bacteriophages and plasmids. In type III CRISPR systems, the recognition of target RNA leads to the synthesis of cyclic oligoadenylate (cOA) second messengers that activate ancillary effector proteins via their CRISPR-associated Rossmann fold (CARF) domains. Commonly, these are ribonucleases (RNases) that unspecifically degrade both invader and host RNA. To mitigate adverse effects on cell growth, ring nucleases can degrade extant cOAs to switch off ancillary nucleases. Here we show that the model organism Synechocystis sp. PCC 6803 harbors functional CARF-domain effector and ring nuclease proteins. We purified and characterized the two ancillary CARF-domain proteins from the III-D type CRISPR system of this cyanobacterium. The Csx1 homolog, SyCsx1, is a cyclic tetraadenylate(cA4)-dependent RNase with a strict specificity for cytosine nucleotides. The second CARF-domain protein with similarity to Csm6 effectors, SyCsm6, did not show RNase activity in vitro but was able to break down cOAs and attenuate SyCsx1 RNase activity. Our data suggest that the CRISPR systems in Synechocystis confer a multilayered cA4-mediated defense mechanism.PMID:36419420 | PMC:PMC9676260 | DOI:10.3389/fmicb.2022.1046388

Microbiome. 2022 Nov 23;10(1):198. doi: 10.1186/s40168-022-01408-7.ABSTRACTBACKGROUND: Dysregulation of gut microbiota-associated tryptophan metabolism has been observed in patients with multiple sclerosis. However, defining direct mechanistic links between this apparent metabolic rewiring and individual constituents of the gut microbiota remains challenging. We and others have previously shown that colonization with the gut commensal and putative probiotic species, Lactobacillus reuteri, unexpectedly enhances host susceptibility to experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. To identify underlying mechanisms, we characterized the genome of commensal L. reuteri isolates, coupled with in vitro and in vivo metabolomic profiling, modulation of dietary substrates, and gut microbiota manipulation.RESULTS: The enzymes necessary to metabolize dietary tryptophan into immunomodulatory indole derivatives were enriched in the L. reuteri genomes, including araT, fldH, and amiE. Moreover, metabolite profiling of L. reuteri monocultures and serum of L. reuteri-colonized mice revealed a depletion of kynurenines and production of a wide array of known and novel tryptophan-derived aryl hydrocarbon receptor (AhR) agonists and antagonists, including indole acetate, indole-3-glyoxylic acid, tryptamine, p-cresol, and diverse imidazole derivatives. Functionally, dietary tryptophan was required for L. reuteri-dependent EAE exacerbation, while depletion of dietary tryptophan suppressed disease activity and inflammatory T cell responses in the CNS. Mechanistically, L. reuteri tryptophan-derived metabolites activated the AhR and enhanced T cell production of IL-17.CONCLUSIONS: Our data suggests that tryptophan metabolism by gut commensals, such as the putative probiotic species L. reuteri, can unexpectedly enhance autoimmunity, inducing broad shifts in the metabolome and immunological repertoire. Video Abstract.PMID:36419205 | DOI:10.1186/s40168-022-01408-7

Cancer Cell Int. 2022 Nov 24;22(1):366. doi: 10.1186/s12935-022-02775-9.ABSTRACTBACKGROUND: Hepatocellular carcinoma (HCC) is one of the deadliest cancers and is mainly developed from chronic liver diseases such as hepatitis-B infection-associated liver cirrhosis (LC). The progression from LC to HCC makes the detection of diagnostic biomarkers to be challenging. Hence, there have been constant efforts to improve on identifying the critical and predictive changes accompanying the disease progression.METHODS: In this study, we looked to using the mass spectrometry mediated spatial metabolomics technique to simultaneous examine hundreds of metabolites in an untargeted fashion. Additionally, metabolic profiles were compared between six subregions within the HCC tissue to collect spatial information.RESULTS: Through those metabolites, altered metabolic pathways in LC and HCC were identified. Specifically, the amino acid metabolisms and the glycerophospholipid metabolisms experienced the most changes. Many of the altered metabolites and metabolic pathways were able to be connected through the urea cycle.CONCLUSIONS: The identification of the key metabolites and pathways can expand our knowledge on HCC metabolic reprogramming and help us exam potential biomarkers for earlier detection of the malignant disease progression.PMID:36419080 | DOI:10.1186/s12935-022-02775-9

Microb Cell Fact. 2022 Nov 23;21(1):241. doi: 10.1186/s12934-022-01973-4.ABSTRACTRecent studies have demonstrated that gut microbiota plays critical roles in various human diseases. High-throughput technology has been widely applied to characterize the microbial ecosystems, which led to an explosion of different types of molecular profiling data, such as metagenomics, metatranscriptomics and metabolomics. For analysis of such data, machine learning algorithms have shown to be useful for identifying key molecular signatures, discovering potential patient stratifications, and particularly for generating models that can accurately predict phenotypes. In this review, we first discuss how dysbiosis of the intestinal microbiota is linked to human disease development and how potential modulation strategies of the gut microbial ecosystem can be used for disease treatment. In addition, we introduce categories and workflows of different machine learning approaches, and how they can be used to perform integrative analysis of multi-omics data. Finally, we review advances of machine learning in gut microbiome applications and discuss related challenges. Based on this we conclude that machine learning is very well suited for analysis of gut microbiome and that these approaches can be useful for development of gut microbe-targeted therapies, which ultimately can help in achieving personalized and precision medicine.PMID:36419034 | DOI:10.1186/s12934-022-01973-4

BMC Plant Biol. 2022 Nov 22;22(1):541. doi: 10.1186/s12870-022-03929-7.ABSTRACTBACKGROUND: Pine wilt disease (PWD) is a destructive disease that endangers pine trees, resulting in the wilting, with yellowing and browning of the needles, and eventually the death of the trees. Previous studies showed that the Avr9/Cf-9 rapidly elicited (PmACRE1) gene was downregulated by Bursaphelenchus xylophilus infection, suggesting a correlation between PmACRE1 expression and pine tolerance. Here, we used the expression of PmACRE1 in Arabidopsis thaliana to evaluate the role of PmACRE1 in the regulation of host defence against B. xylophilus infection.RESULTS: Our results showed that the transformation of PmACRE1 into A. thaliana enhanced plant resistance to the pine wood nematode (PWN); that is, the leaves of the transgenic line remained healthy for a longer period than those of the blank vector group. Ascorbate peroxidase (APX) activity and total phenolic acid and total flavonoid contents were higher in the transgenic line than in the control line. Widely targeted metabolomics analysis of the global secondary metabolites in the transgenic line and the vector control line showed that the contents of 30 compounds were significantly different between these two lines; specifically, the levels of crotaline, neohesperidin, nobiletin, vestitol, and 11 other compounds were significantly increased in the transgenic line. The studies also showed that the ACRE1 protein interacted with serine hydroxymethyltransferase, catalase domain-containing protein, myrosinase, dihydrolipoyl dehydrogenase, ketol-acid reductoisomerase, geranylgeranyl diphosphate reductase, S-adenosylmethionine synthase, glutamine synthetase, and others to comprehensively regulate plant resistance.CONCLUSIONS: Taken together, these results indicate that PmACRE1 has a potential role in the regulation of plant defence against PWNs.PMID:36418942 | DOI:10.1186/s12870-022-03929-7

Methods Mol Biol. 2023;2583:149-156. doi: 10.1007/978-1-0716-2752-5_13.ABSTRACTDiverse metabolic disorders can disrupt brain growth, and analyzing metabolism in animal models of microcephaly may reveal new mechanisms of pathogenesis. The metabolism of functioning cells in a living organism is constantly changing in response to a changing environment, circadian rhythms, consumed food, drugs, progressing sicknesses, aging, and many other factors. Metabolic profiling can give important insights into the working machinery of the cell. However, a frozen snapshot of the interconnected, complex network of reactions gives very limited information about this system. Flux analysis using stable isotope labels enables more robust metabolic studies that consider interrogate metabolite processing and changes in molecular concentrations over time.PMID:36418732 | DOI:10.1007/978-1-0716-2752-5_13

Methods Mol Biol. 2023;2583:3-7. doi: 10.1007/978-1-0716-2752-5_1.ABSTRACTBrain growth reflects the proliferation dynamics of neural progenitors, and understanding brain growth requires molecular, genetic, and functional studies of these specific cells. Cerebellar granule neuron progenitors (CGNPs) proliferate in the early postnatal period in both mice and humans, to generate the largest population of neurons in the central nervous system. CGNPs present a large, spatially segregated source of neural progenitors with a consistent, well-characterized temporal pattern of proliferation and differentiation that facilitates analysis. Dissociating of CGNPs with the methods below will generate a suspension of primary neural progenitors harvested from the postnatal brain that may be used for diverse experimental analyses including cell culture, protein extraction, flow cytometry, metabolomic analysis, and transcriptomic analysis with single-cell resolution (scRNA-seq).PMID:36418720 | DOI:10.1007/978-1-0716-2752-5_1