PubMed

FEMS Microbiol Rev. 2023 Feb 1:fuad001. doi: 10.1093/femsre/fuad001. Online ahead of print.ABSTRACTMolecular technologies including high-throughput sequencing have expanded our perception of the microbial world. Unprecedented insights into the composition and function of microbial communities has generated large interest, with numerous landmark studies published in recent years relating the important roles of microbiomes and the environment-especially diet and nutrition-in human, animal, and global health. As such, food microbiomes represent an important cross-over between the environment and host. This is especially true of fermented food microbiomes, which actively introduce microbial metabolites and to a lesser extent, live microbes into the human gut. Here we discuss the history of fermented foods, and examine how molecular approaches have advanced research of these fermented foods over the past decade. We highlight how various molecular approaches have helped us to understand the ways in which microbes shape the qualities of these products, and we summarise the impacts of consuming fermented foods on the gut. Finally, we explore how advances in bioinformatics could be leveraged to enhance our understanding of fermented foods. This review highlights how integrated molecular approaches are changing our understanding of the microbial communities associated with food fermentation, the creation of unique food products, and their influences on the human microbiome and health.PMID:36725208 | DOI:10.1093/femsre/fuad001

Adv Cancer Res. 2023;157:57-81. doi: 10.1016/bs.acr.2022.07.002. Epub 2022 Oct 1.ABSTRACTThe development of robust cancer biomarkers is the most effective way to improve overall survival, as early detection and treatment leads to significantly better clinical outcomes. Many of the cancer biomarkers that have been identified and are clinically utilized are glycoproteins, oftentimes a specific glycoform. Aberrant glycosylation is a common theme in cancer, with dysregulated glycosylation driving tumor initiation and metastasis, and abnormal glycosylation can be detection both on the tissue surface and in serum. However, most cancer types are heterogeneous in regard to tumor genomics, and this heterogeneity extends to cancer glycomics. This limits the sensitivity of standalone glycan-based biomarkers, which has slowed their implementation clinically. However, if targeted biomarker development can take into account genomic tumor information, the development of complementary biomarkers that target unique cancer subgroups can be accomplished. This idea suggests the need for algorithm-based cancer biomarkers, which can utilize multiple biomarkers along with relevant demographic information. This concept has already been established in the detection of hepatocellular carcinoma with the GALAD score, and an algorithm-based approach would likely be effective in improving biomarker sensitivity for additional cancer types. In order to increase cancer diagnostic biomarker sensitivity, there must be more targeted biomarker development that considers tumor genomic, proteomic, metabolomic, and clinical data while identifying tumor biomarkers.PMID:36725113 | DOI:10.1016/bs.acr.2022.07.002

Ecotoxicol Environ Saf. 2023 Jan 30;252:114585. doi: 10.1016/j.ecoenv.2023.114585. Online ahead of print.ABSTRACTMarine and intertidal heavy metal pollution has been a major concern in recent years. Tachypleus tridentatus has existed on earth for more than 430 million years. It has suffered a sharp decline in population numbers caused by environmental pollution and anthropogenic disturbance for almost 40 years. However, the effects of heavy metal pollution on juvenile T. tridentatus have not been reported. Here we show the mechanism of cadmium (Cd) detoxification in juvenile T. tridentatus using integrated antioxidant indexes and transcriptomic and metabolomic analysis. High Cd2+ concentration caused oxidative stress in juvenile T. tridentatus. The hazards increase with increasing Cd2+ concentration in juvenile T. tridentatus. Transcriptomics and metabolomics analyses concluded that high Cd2+ concentration resulted in the imbalance of glycerophospholipid metabolism in juvenile T. tridentatus to detoxify Cd. Our results offer a rationale for protective measures and further studies of heavy metal stress in T. tridentatus.PMID:36724710 | DOI:10.1016/j.ecoenv.2023.114585

Plant Physiol Biochem. 2023 Jan 28;196:210-221. doi: 10.1016/j.plaphy.2023.01.050. Online ahead of print.ABSTRACTAs a well-recognized traditional Chinese medicine (TCM), immature fruits of Citrus grandis 'Tomentosa' (CGT) serve to cure chronic cough in humans. Specialized metabolites including flavonoids may have contribute to this curing effect. Knowledge about the molecular mechanisms underlying flavonoid biosynthesis in 'Tomentosa' fruits will, therefore, support the breeding of varieties with improved medicinal properties. Hence, we profiled the transcriptomes and metabolites of the fruits of two contrasting C. grandis varieties, namely 'Zheng-Mao' ('ZM') used in TCM production, and a locally cultivated pomelo, namely 'Guang-Qing' ('GQ'), at four developmental stages. A total of 39 flavonoids, including 14 flavanone/flavone, 5 isoflavonoids, 12 flavonols, and 6 anthocyanins, were identified, and 16 of which were quantitatively determined in the fruits of the two varieties. We found that 'ZM' fruits contain more flavonoids than 'GQ'. Specifically, rhoifolin levels were significantly higher in 'ZM' than in 'GQ'. We annotated 31,510 genes, including 1,387 previously unknown ones, via transcriptome sequencing of 'ZM' and 'GQ.' A total of 646 genes were found to be differentially expressed between 'ZM' and 'GQ' throughout at all four fruit developmental stages, indicating that they are robust expression markers for future breeding programs. Weighted gene co-expression network analysis identified 18 modules. Combined transcriptional and metabolic analysis revealed 25 genes related to flavonoid biosynthesis and 16 transcriptional regulators (MYBs, bHLHs, WD40) that may be involved in the flavonoids biosynthesis in C. grandis 'Tomentosa' fruits.PMID:36724705 | DOI:10.1016/j.plaphy.2023.01.050

Meat Sci. 2023 Jan 19;199:109121. doi: 10.1016/j.meatsci.2023.109121. Online ahead of print.ABSTRACTInsights into changes in microorganisms and metabolites in irradiated marbled beef may help elucidate the beneficial effects of irradiation on prolonging the shelf life of meat. In this study, 16S rRNA gene sequencing, ultra-high-performance liquid chromatography-tandem mass spectrometry, and Pearson's correlation analyses were conducted to detect key microorganisms, core metabolites, and potential correlation between the microbiome and metabolome in marbling beef. Microbiome analysis showed that irradiation effectively eradicated the spoilage bacterium Leuconostoc and reduced the proportions of Carnobacterium and Lactobacillus in marbled beef. Additionally, results of metabolomic analysis involving irradiated marbled beef revealed that metabolites with significant differences were mainly organic acids and their derivatives, lipids, and lipid-like molecules, including six core metabolites. Furthermore, a significant correlation between key bacteria and metabolites was observed. Carnobacterium, Lactobacillus, and Leuconostoc affected the accumulation of core metabolites in irradiated marbled beef by influencing amino acid and lipid metabolism. Characterization of the microbiota and metabolites, as well as clarification of their correlation, can contribute to a better understanding of the mechanisms whereby irradiation helps maintain meat quality.PMID:36724675 | DOI:10.1016/j.meatsci.2023.109121

Heart Lung. 2023 Jan 30;59:52-60. doi: 10.1016/j.hrtlng.2023.01.011. Online ahead of print.ABSTRACTBACKGROUND: There is currently a need to identify metabolomic responses to acute exercise in chronic obstructive pulmonary disease (COPD).OBJECTIVE: We investigated the metabolomic, oxidative, and inflammatory responses to constant (CE) and intermittent (IE) work rate exercises in COPD.METHODS: Sixteen males with COPD performed a symptom-limited incremental cycle exercise test (ICE). Metabolomic, oxidative, and inflammatory responses to CE and IE (based on the performance of ICE) were analyzed in the plasma.RESULTS: Fructose-6-phosphate, 3-phosphoglyceric acid, l-carnitine, and acylcarnitines levels were significantly decreased, whereas alpha-ketoglutaric, malic, 2-hydroxybutyric, and 3-hydroxybutyric acids were increased, after CE and IE (p<0.05). Increases in citric, isocitric, and lactic acids, as well as decreases in pyruvic and oxalic acids, were only present with IE (p<0.05). Isoleucine was decreased after both exercises (p<0.05). We observed an increase in inosine-5'-diphosphate, uric acid, ascorbic acid, and pantothenic acid, as well as a decrease in 5-hydroxymethyluridine, threonic acid, and dehydroascorbic acid, after IE (p<0.05). Catalase, reduced glutathione, and total antioxidant status difference values for both exercises were similar (p>0.05). The change in glutathione peroxidase (GPx) with CE was more significant than that with IE (p = 0.004). The superoxide dismutase change was greater with IE than with CE (p = 0.015). There were no significant changes in inflammatory markers after exercise (p>0.05).CONCLUSION: CE and IE cause isoleucine, l-carnitine, and acylcarnitine levels to decrease, whereas ketone bodies were increased, thus indicating the energy metabolism shift from carbohydrates to amino acid utilization and lipid metabolism in COPD. Compared with CE, IE produces significant changes in more metabolomics in terms of carbohydrates, lipids, amino acids, nucleotides, and vitamins. Acute CE and IE alter circulating GPx levels in COPD.PMID:36724589 | DOI:10.1016/j.hrtlng.2023.01.011

Anal Chem. 2023 Feb 1. doi: 10.1021/acs.analchem.2c04360. Online ahead of print.ABSTRACTMass spectrometry imaging (MSI) is a powerful tool that can be used to simultaneously investigate the spatial distribution of different molecules in samples. However, it is difficult to comprehensively analyze complex biological systems with only a single analytical technique due to different analytical properties and application limitations. Therefore, many analytical methods have been combined to extend data interpretation, evaluate data credibility, and facilitate data mining to explore important temporal and spatial relationships in biological systems. Image registration is an initial and critical step for multimodal imaging data fusion. However, the image registration of multimodal images is not a simple task. The property difference between each data modality may include spatial resolution, image characteristics, or both. The image registrations between MSI and different imaging techniques are often achieved indirectly through histology. Many methods exist for image registration between MSI data and histological images. However, most of them are manual or semiautomatic and have their prerequisites. Here, we built MSI Registrar (MSIr), a web service for automatic registration between MSI and histology. It can help to reduce subjectivity and processing time efficiently. MSIr provides an interface for manually selecting region of interests from histological images; the user selects regions of interest to extract the corresponding spectrum indices in MSI data. In the performance evaluation, MSIr can quickly map MSI data to histological images and help pinpoint molecular components at specific locations in tissues. Most registrations were adequate and were without excessive shifts. MSIr is freely available at https://msir.cmdm.tw and https://github.com/CMDM-Lab/MSIr.PMID:36724516 | DOI:10.1021/acs.analchem.2c04360

Sci Adv. 2023 Feb 3;9(5):eade8641. doi: 10.1126/sciadv.ade8641. Epub 2023 Feb 1.ABSTRACTPhosphatidylinositol (PI)regulating enzymes are frequently altered in cancer and have become a focus for drug development. Here, we explore the phosphatidylinositol-5-phosphate 4-kinases (PI5P4K), a family of lipid kinases that regulate pools of intracellular PI, and demonstrate that the PI5P4Kα isoform influences androgen receptor (AR) signaling, which supports prostate cancer (PCa) cell survival. The regulation of PI becomes increasingly important in the setting of metabolic stress adaptation of PCa during androgen deprivation (AD), as we show that AD influences PI abundance and enhances intracellular pools of PI-4,5-P2. We suggest that this PI5P4Kα-AR relationship is mitigated through mTORC1 dysregulation and show that PI5P4Kα colocalizes to the lysosome, the intracellular site of mTORC1 complex activation. Notably, this relationship becomes prominent in mouse prostate tissue following surgical castration. Finally, multiple PCa cell models demonstrate marked survival vulnerability following stable PI5P4Kα inhibition. These results nominate PI5P4Kα as a target to disrupt PCa metabolic adaptation to castrate resistance.PMID:36724278 | DOI:10.1126/sciadv.ade8641

Sci Transl Med. 2023 Feb;15(681):eabq4126. doi: 10.1126/scitranslmed.abq4126. Epub 2023 Feb 1.ABSTRACTSulfonylureas (SUs) are effective and affordable antidiabetic drugs. However, chronic use leads to secondary failure, limiting their utilization. Here, we identify cytochrome b5 reductase 3 (Cyb5r3) down-regulation as a mechanism of secondary SU failure and successfully reverse it. Chronic exposure to SU lowered Cyb5r3 abundance and reduced islet glucose utilization in mice in vivo and in ex vivo murine islets. Cyb5r3 β cell-specific knockout mice phenocopied SU failure. Cyb5r3 engaged in a glucose-dependent interaction that stabilizes glucokinase (Gck) to maintain glucose utilization. Hence, Gck activators can circumvent Cyb5r3-dependent SU failure. A Cyb5r3 activator rescued secondary SU failure in mice in vivo and restored insulin secretion in ex vivo human islets. We conclude that Cyb5r3 is a key factor in the secondary failure to SU and a potential target for its prevention, which might rehabilitate SU use in diabetes.PMID:36724243 | DOI:10.1126/scitranslmed.abq4126

J Appl Microbiol. 2022 Dec 14:lxac031. doi: 10.1093/jambio/lxac031. Online ahead of print.ABSTRACTAIMS: Propolis is a resinous bee product containing several hundred biologically active compounds. Although the antibacterial activity of propolis has been demonstrated in many in vitro studies, less is known about its mode of action. In this study, we aimed to shed some light on the antibacterial mechanism of action of propolis against Escherichia coli BW25113 using a nuclear magnetic resonance (NMR) based metabolomics approach.METHODS: E. coli BW25113 cells were subjected to different sub-lethal concentrations (0, 2, 4, and 6 mg/mL) of Turkish propolis water extract (PWE). The 500-MHz 1H NMR spectroscopy was then employed to ascertain the metabolic profiles of E. coli extracts.RESULTS: A total of 52 metabolites were identified from the NMR spectra, belonging to 17 main classes, such as amino acids and peptides, purines, and fatty acids. Twelve out of these 52 metabolites displayed remarkable changes at all tested PWE concentrations when compared to control conditions (P < .05). Levels of 28 more metabolites were significantly altered in at least one of the three PWE treatments. The results of partial least squares discriminant analysis showed that there was a clear separation between control and propolis-treated cells and that putrescine, adenine, adenosine, guanosine, glucose, N6-acetyllysine, and acetamide had the highest effect on group differentiation. Finally, quantitative pathway analysis revealed that purine metabolism was significantly affected by PWE treatments.CONCLUSIONS: Our results suggest that PWE inhibits the growth of E. coli BW25113 by affecting nucleic acid metabolism to a great extent. To the best of our knowledge, this is the first study to evaluate the global metabolic response of a bacterium to propolis.PMID:36724215 | DOI:10.1093/jambio/lxac031

PLoS One. 2023 Feb 1;18(2):e0280382. doi: 10.1371/journal.pone.0280382. eCollection 2023.ABSTRACTContaminants of emerging concern pose a serious hazard to aquatic wildlife, especially freshwater mussels. The growing number of contaminants in aquatic systems requires scientists and managers to prioritize contaminants that are most likely to elicit a biological response for further monitoring and toxicological testing. The objectives of this study were to identify a sub-category of contaminants most likely to affect Pyganodon grandis and to describe alterations in metabolites and gene expression between various sites. Mussels were deployed in cages for two weeks at four sites along the Maumee River Basin, Ohio, USA. Water samples were analyzed for the presence of 220 contaminants. Hemolymph samples were collected for metabolomics and analyzed using mass spectrometry. Contaminants that significantly covaried with metabolites were identified using partial least-squares (PLS) regression. Tissue samples were collected for transcriptomics, RNA was sequenced using an Illumina HiSeq 2500, and differential expression analysis was performed on assembled transcripts. Of the 220 targeted contaminants, 69 were detected in at least one water sample. Of the 186 metabolites detected in mussel hemolymph, 43 showed significant differences between the four sites. The PLS model identified 44 contaminants that significantly covaried with changes in metabolites. A total of 296 transcripts were differentially expressed between two or more sites, 107 received BLAST hits, and 52 were annotated and assigned to one or more Gene Ontology domains. Our analyses reveal the contaminants that significantly covaried with changes in metabolites and are most likely to negatively impact freshwater mussel health and contribute to ongoing population declines in this group of highly endangered animals. Our integration of "omics" technologies provides a broad and in-depth assessment of the short-term effects of contaminants on organismal physiology. Our findings highlight which contaminants are most likely to be causing these changes and should be prioritized for more extensive toxicological testing.PMID:36724160 | DOI:10.1371/journal.pone.0280382

Am J Physiol Endocrinol Metab. 2023 Feb 1. doi: 10.1152/ajpendo.00231.2022. Online ahead of print.ABSTRACTObesity is one of the leading non-communicable diseases in the world. Despite intense efforts to develop strategies to prevent and treat obesity, its prevalence continues to rise worldwide. A recent study has shown that the tricarboxylic acid intermediate succinate increases body energy expenditure by promoting brown adipose tissue thermogenesis through the activation of uncoupling protein-1; this has generated interest surrounding its potential usefulness as an approach to treat obesity. It is currently unknown how succinate impacts brown adipose tissue protein expression, and how exogenous succinate impacts body mass reduction promoted by a drug approved to treat human obesity, the glucagon-like-1 receptor agonist, liraglutide. In the first part of this study, we used bottom-up shotgun proteomics to determine the acute impact of exogenous succinate on the brown adipose tissue. We show that succinate rapidly affects the expression of 177 brown adipose tissue proteins, which are mostly associated with mitochondrial structure and function. In the second part of this study, we performed a short-term preclinical pharmacological intervention, treating diet-induced obese mice with a combination of exogenous succinate and liraglutide. We show that the combination was more efficient than liraglutide alone in promoting body mass reduction, food energy efficiency reduction, food intake reduction and an increase in body temperature. Using serum metabolomics analysis, we showed that succinate, but not liraglutide, promoted a significant increase in the blood levels of several medium- and long-chain fatty acids. In conclusion, exogenous succinate promotes rapid changes in brown adipose tissue mitochondrial proteins, and when used in association with liraglutide, increases body mass reduction.PMID:36724126 | DOI:10.1152/ajpendo.00231.2022

J Urol. 2023 Feb 1:101097JU0000000000003200. doi: 10.1097/JU.0000000000003200. Online ahead of print.ABSTRACTOBJECTIVE: We sought to determine microbe-metabolite composition and interactions within indwelling ureteral stent biofilms, determine their association with patient factors including infection, and reconstitute biofilm formation on relevant surface materials in vitro.MATERIAL AND METHODS: Upon ureteral stent removal from patients, proximal and distal ends were swabbed. Samples were analyzed by 16S next-generation sequencing and metabolomics. A continuous-flow stir-tank bioreactor was used to reconstitute and quantify in vitro biofilm formation from stent-isolated bacteria on stent-related materials including silicone, PTFE, polyurethane, polycarbonate, and titanium. Diversity, relative abundance, and association with clinical factors were analyzed with ANOVA and Bonferroni t-tests or PERMANOVA. Biofilm deposition by microbial strain and device material type were analyzed using plate counts and scanning electron microscopy following bioreactor incubation.RESULTS: All 73 samples from 37 ureteral stents harbored microbiota. Specific genera were more abundant in samples from stents wherein there was antibiotic exposure during indwelling time (Escherichia/Shigella, Pseudomonas, Staphylococcus, Ureaplasma), and in those associated with infection (Escherichia/Shigella, Ureaplasma). The enriched interaction subnetwork in stent-associated infection included Ureaplasma and metabolite 9-methyl-7-bromoeudistomin. Strains identified as clinically relevant and central to interaction networks all reconstituted biofilm in vitro, with differential formation by strain (Enterococcus faecalis most) and material type (titanium least).CONCLUSIONS: Ureteral stent biofilms exhibit patterns unique to stent-associated infection and antibiotic exposure during indwelling time. Microbes isolated from stents reconstituted biofilm formation in vitro. This work provides a platform to test novel materials, evaluate new coatings for anti-biofilm properties, and explore commensal strain use for bacterial interference against pathogens.PMID:36724057 | DOI:10.1097/JU.0000000000003200

Curr Microbiol. 2023 Feb 1;80(3):90. doi: 10.1007/s00284-023-03195-2.ABSTRACTThis study investigated the bacterial and postbiotic potential of three Anatolian bee bread samples obtained from different regions of Turkey (Marmara, Aegean, and Mediterranean) and offered for human consumption. The families most commonly found in Anatolian bee bread were Lactobacillaceae, Oscillospiraceae, Bacteroidaceae, Prevotellaceae, and Lachnospiraceae. Lactobacillus delbruckeii was highly abundant, but also other beneficial bacteria, known to be next-generation probiotics, were revealed in bee bread, such as Prevotalla copri, Faecalibacterium prausnitzii, and Akkermansia muciniphila. Apart from these beneficial bacteria, bee bread samples also harbored undesired bacteria such as Phocaeicola vulgatus, Phocaeicola dorei, and Clostridium perfringens. Fatty acid composition showed that bee bread samples had butyric acid, a short-chain fatty acid, as a postbiotic. Additionally, polyunsaturated fatty acids were also found such as alfa-linolenic acid and eicosadienoic acid. The fatty acids with the highest amounts were palmitic acid (~ 30%), stearic acid (~ 17%), and alpha-linolenic acid (~ 12%). One of the samples exhibited antimicrobial activity against Staphylococcus aureus.PMID:36723722 | DOI:10.1007/s00284-023-03195-2

Clin Oral Investig. 2023 Feb 1. doi: 10.1007/s00784-023-04878-7. Online ahead of print.ABSTRACTThe interface of molecular science and technology is guiding the transformation of personalized to precision healthcare. The application of proteomics, genomics, transcriptomics, and metabolomics is shaping the suitability of biomarkers for disease. Prior validation of such biomarkers in large and diverse patient cohorts helps verify their clinical usability. Incorporation of molecular discoveries into routine clinical practice relies on the development of customized assays and devices that enable the rapid delivery of analytical data to the clinician, while the patient is still in session. The present perspective review addresses this topic under the prism of precision periodontal care. Selected promising research attempts to innovate technological platforms for oral diagnostics are brought forward. Focus is placed on (a) the suitability of saliva as a conveniently sampled biological specimen for assessing periodontal health, (b) proteomics as a high-throughput approach for periodontal disease biomarker identification, and (c) chairside molecular diagnostic assays as a technological funnel for transitioning from the laboratory benchtop to the clinical point-of-care.PMID:36723713 | DOI:10.1007/s00784-023-04878-7

Phytother Res. 2023 Feb 1. doi: 10.1002/ptr.7704. Online ahead of print.ABSTRACTNeuropathic pain (NeP) is a major health concern. Due to the complex pathological mechanisms, management of NeP is challenging. Emodin, a natural anthraquinone derivative, exerts excellent analgesic effects. However, its mechanisms of action are still poorly understood. In this study, we investigated the mechanisms underlying pain-relief effects of emodin in the cerebral cortex using proteomic and metabolomic approaches. After 15 days of emodin administration, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in the emodin groups were significantly higher than those in the chronic constriction injury (CCI) group (p < .05), suggesting emodin treatment could reverse CCI-induced hyperalgesia. Emodin treatment evoked the expression alteration of 402 proteins (153 up-regulated and 249 down-regulated) in the CCI models, which were primarily involved in PI3K/AKT signaling pathway, gamma-aminobutyric acid (GABA) receptor signaling, complement and coagulation cascades, cGMP/PKG signaling pathway, MAPK signaling pathway, and calcium signaling pathway. In parallel, emodin intervention regulated the abundance alteration of 27 brain metabolites (20 up-regulated and 7 down-regulated) in the CCI rats, which were primarily implicated in carbon metabolism, biosynthesis of amino acids, pentose phosphate pathway, and glucagon signaling pathway. After a comprehensive analysis and western blot validation, we demonstrated that emodin alleviated NeP mainly through regulating GABAergic pathway and PI3K/AKT/NF-κB pathway.PMID:36723382 | DOI:10.1002/ptr.7704

Anal Methods. 2023 Feb 1. doi: 10.1039/d2ay01446g. Online ahead of print.ABSTRACTAspergillus fumigatus has the potential to degrade lignocellulosic biomass, but the degradation mechanism is not clear. The purpose of this study is to analyze the differential proteins and metabolites produced by Aspergillus fumigatus G-13 in the degradation of different lignin model compounds. Ferulic acid, sinapic acid, and p-coumaric acid were used as carbon sources. By controlling the culture conditions, and adding a cellulose co-substrate and an auxiliary carbon source, the enzymatic production law of three lignin model compounds degraded by Aspergillus fumigatus G-13 was investigated. Proteomics and metabolomics analysis were conducted for the two groups with the largest difference in enzyme activity expression. The results showed that a total of 1447 peptides were identified by proteomics analysis. Among them, 134 proteins were significantly changed, 73 proteins were up-regulated, and 61 proteins were down-regulated. The key proteins that degrade lignin model compounds are catechol dioxygenase, glutathione reductase, dextranase, isoamyl alcohol oxidase, glyceraldehyde-3-phosphate dehydrogenase and superoxide dismutase. Enrichment analysis of differential metabolite functions revealed that Aspergillus fumigatus G-13 is associated with several pathways related to the degradation of lignin. Among them, starch and sucrose metabolism, pentose phosphate pathway, glutathione metabolism, and the ortho-cleavage pathway of dihydroxylated aromatic rings are closely related to lignin degradation. The information presented in this paper will be helpful for future research on the degradation or depolymerization of natural lignocellulosic substrates.PMID:36723181 | DOI:10.1039/d2ay01446g

Schizophr Bull. 2023 Feb 1:sbac202. doi: 10.1093/schbul/sbac202. Online ahead of print.ABSTRACTBACKGROUND AND HYPOTHESIS: Antipsychotics (APs), the cornerstone of schizophrenia treatment, confer a relatively high risk of constipation. However, the mechanisms underpinning AP-induced constipation are poorly understood. Thus, we hypothesized that (1) schizophrenia patients with AP-induced constipation have distinct metabolic patterns; (2) there is more than one mechanism at play in producing this adverse drug effect; and (3) AP-associated changes in the gut microbiome are related to the altered metabolic profiles.STUDY DESIGN: Eighty-eight schizophrenia patients, including 44 with constipation (C) and 44 matched patients without constipation (NC), were enrolled in this study. Constipation was diagnosed by Rome IV criteria for constipation and colonic transit time using radiopaque markers (ROMs) while severity was evaluated with the Bristol Stool Form Scale (BSS) and Constipation Assessment Scale (CAS). Fasting blood samples were drawn from all participants and were subjected to non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis.STUDY RESULTS: Eleven metabolites were significantly altered in AP-induced constipation which primarily disturbed sphingolipid metabolism, choline metabolism, and sphingolipid signaling pathway (P value < .05, FDR < 0.05). In the C group, changes in the gut bacteria showed a certain degree of correlation with 2 of the significantly altered serum metabolites and were associated with alterations in choline metabolism.CONCLUSIONS: Our findings indicated that there were disturbances in distinct metabolic pathways that were associated with AP-induced constipation. In addition, this study presents evidence of a link between alterations in the gut microbiome and host metabolism which provides additional mechanistic insights on AP-induced constipation.PMID:36723169 | DOI:10.1093/schbul/sbac202

Mol Omics. 2023 Jan 30. doi: 10.1039/d2mo00220e. Online ahead of print.ABSTRACTCisplatin is commonly used in combination with other cytotoxic agents as a standard treatment regimen for a variety of solid tumors, such as lung, ovarian, testicular, and head and neck cancers. However, the effectiveness of cisplatin is accompanied by toxic side effects, for instance, nephrotoxicity and neurotoxicity. The response of tumors to cisplatin treatment involves multiple physiological processes, and the efficacy of chemotherapy is limited by the intrinsic and acquired resistance of tumor cells. Although enormous efforts have been made toward molecular mechanisms of cisplatin resistance, the development of omics provides new insights into the understanding of cisplatin resistance at genome, transcriptome, proteome, metabolome and epigenome levels. Mechanism studies using different omics approaches revealed the necessity of multi-omics applications, which provide information at different cellular function levels and expand our recognition of the peculiar genetic and phenotypic heterogeneity of cancer. The present work systematically describes the underlying mechanisms of cisplatin resistance in different tumor types using multi-omics approaches. In addition to the classical mechanisms such as enhanced drug efflux, increased DNA damage repair and changes in the cell cycle and apoptotic pathways, other changes like increased protein damage clearance, increased protein glycosylation, enhanced glycolytic process, dysregulation of the oxidative phosphorylation pathway, ferroptosis suppression and mRNA m6A methylation modification can also induce cisplatin resistance. Therefore, utilizing the integrated omics to identify key signaling pathways, target genes and biomarkers that regulate chemoresistance are essential for the development of new drugs or strategies to restore tumor sensitivity to cisplatin.PMID:36723121 | DOI:10.1039/d2mo00220e

Microbiol Spectr. 2023 Feb 1:e0327522. doi: 10.1128/spectrum.03275-22. Online ahead of print.ABSTRACTWe compared changes induced by the addition of 100 nM and 5 mM glucose on the proteome and metabolome complements in Synechococcus sp. strains WH8102, WH7803, and BL107 and Prochlorococcus sp. strains MED4, SS120, and MIT9313, grown either under standard light conditions or in darkness. Our results suggested that glucose is metabolized by these cyanobacteria, using primarily the oxidative pentoses and Calvin pathways, while no proof was found for the involvement of the Entner-Doudoroff pathway in this process. We observed differences in the effects of glucose availability, both between genera and between Prochlorococcus MED4 and SS120 strains, which might be related to their specific adaptations to the environment. We found evidence for fermentation in Prochlorococcus sp. strain SS120 and Synechococcus sp. strain WH8102 after 5 mM glucose addition. Our results additionally suggested that marine cyanobacteria can detect nanomolar glucose concentrations in the environment and that glucose might be used to sustain metabolism under darkness. Furthermore, the KaiB and KaiC proteins were also affected in Synechococcus sp. WH8102, pointing to a direct link between glucose assimilation and circadian rhythms in marine cyanobacteria. In conclusion, our study provides a wide overview on the metabolic effects induced by glucose availability in representative strains of the diverse marine picocyanobacteria, providing further evidence for the importance of mixotrophy in marine picocyanobacteria. IMPORTANCE Glucose uptake by marine picocyanobacteria has been previously described and strongly suggests they are mixotrophic organisms (capable of using energy from the sun to make organic matter, but also to directly use organic matter from the environment when available). However, a detailed analysis of the effects of glucose addition on the proteome and metabolome of these microorganisms had not been carried out. Here, we analyzed three Prochlorococcus sp. and three Synechococcus sp. strains which were representative of several marine picocyanobacterial clades. We observed differential features in the effects of glucose availability, depending on both the genus and strain; our study illuminated the strategies utilized by these organisms to metabolize glucose and showed unexpected links to other pathways, such as circadian regulation. Furthermore, we found glucose addition had profound effects in the microbiome, favoring the growth of coexisting heterotrophic bacteria.PMID:36722960 | DOI:10.1128/spectrum.03275-22