PubMed

Food Res Int. 2023 Feb;164:112361. doi: 10.1016/j.foodres.2022.112361. Epub 2023 Jan 2.ABSTRACTThis study investigated the transport stress (crowding stress and duration) on the physicochemical properties, energy metabolism and antioxidant enzyme activities of the red swamp crayfish (Procambarus clarkii) tail muscle (CTM). Besides, transcriptomic and metabolomic were conducted to elucidate the possible mechanism of CTM alternations during transport stress. The survival rate of crayfish gradually decreased with the external crowding stress and crowding time increasing. The transport stress also led to the increased distance among muscle fibers, water mobility and energy consumption, and the decreased of water holding capacity (WHC), hardness of CTM. The hepatopancreas exhibited more sensitive to crowding stress than muscle. The multi-omics analysis revealed that transport stress could interfere the translation and protein folding functions of ribosomal proteins, fatty acid metabolism and degradation, physiological functions of mitochondria in CTM. This study could provide critical information to increase the understanding of the regulation mechanism of crayfish when subjected to transport stress.PMID:36737949 | DOI:10.1016/j.foodres.2022.112361

Food Res Int. 2023 Feb;164:112347. doi: 10.1016/j.foodres.2022.112347. Epub 2022 Dec 26.ABSTRACTFenugreek (Trigonella foenum-graecum L.) is an important food and spice with bioactive compounds against diabetes. In this study, fenugreek seeds germinating in darkness for 72 h were studied using quantification of trigonelline and 4-hydroxyisoleucine and an LC-ESI-MS/MS-based metabolomic approach capable of accurately estimating 237 features from various primary and specialized compound classes. During germination, the concentrations of trigonelline and 4-hydroxyisoleucine rose by 33.5% and 33.3%, respectively. At the same time, untargeted metabolomics revealed 9 putative flavonoids increasing 1.19- to 2.77-fold compared to the dormant seeds. A set of 19 steroid saponins rose by 1.08- to 31.86-fold. Primary metabolites however showed much more variability: abundance changes in amino acid derivatives, peptides and saccharides fell in the 0.09- to 22.25-fold, 0.93- to 478.79-fold and 0.36- to 941.58-fold ranges, respectively. To increase biosynthesis of specialized metabolites during germination, sprouts were exposed to 1-100 mM methyl jasmonate (MeJA) and methyl salicylate (MeSA). The hormone treatments affected normal metabolism: 67.1-83.1 % and 64.1-83.5 % of compounds showed a reduction compared to the controls in 100 mM MeJA and MeSA treatments at different sampling time points. Contrary to expectations, the abundance of flavonoids decreased, compared to the control sprouts (0.75- and 0.68-fold change medians, respectively). The same was observed for most, but not all steroid saponins. The quality-controlled untargeted metabolomics approach proved to yield excellent insight into the metabolic changes during germination of fenugreek. The results suggest that although fenugreek germination causes major shifts in plant metabolism, there are no major qualitative changes in bioactive specialized metabolites during the first three days. This stability likely translates into good bioactivity that is similar to that of the seeds. Because the large changes in the primary metabolites likely alter the nutritive value of the seed, further studies are warranted.PMID:36737938 | DOI:10.1016/j.foodres.2022.112347

Food Res Int. 2023 Feb;164:112334. doi: 10.1016/j.foodres.2022.112334. Epub 2022 Dec 20.ABSTRACTTartary buckwheat (TB) sprout is a kind of novel nutritional vegetable, but its consumption was limited by low biomass and thin hypocotyl. The tetraploid TB sprouts was considered to be able to solve this issue. However, the nutritional quality of tetraploid TB sprouts and differences between conventional (diploid) and tetraploid TB sprouts remain unclear. In this study, the morphological traits, nutrient compositions and metabolome changes of diploid and tetraploid TB sprouts were analyzed. The water, pigments and minerals contents of TB sprouts increased during sprouting, while the contents of total soluble protein, reducing sugar, cellulose, and total phenol decreased. Compared with diploid sprouts, tetraploid sprouts had higher biomass and thicker hypocotyl. Tetraploid sprouts had higher ash and carotenoid contents, but had lower phenol and flavonoid accumulation. 677 metabolites were identified in TB sprouts by UPLC-MS analysis, including 62 diseases-resistance metabolites and 43 key active ingredients. Some key bioactive metabolites, such as rimonabant, quinapril, 1-deoxynojirimycin and miglitol, were identified. 562 differential expressed metabolites (DEMs) were identified during sprouting with seven accumulation patterns, and five hormones were found to be involved in sprout development. Additionally, 209 DEMs between diploid and tetraploid sprouts were found, and some key bioactive metabolites were induced by chromosome doubling such as mesoridazine, amaralin, atractyloside A, rhamnetin and Qing Hau Sau. This work lays a basis for the development and utilization of TB sprouts and provides evidence for the selection of tetraploid varieties to produce sprouts with high biomass and quality.PMID:36737927 | DOI:10.1016/j.foodres.2022.112334

Food Res Int. 2023 Feb;164:112314. doi: 10.1016/j.foodres.2022.112314. Epub 2022 Dec 7.ABSTRACTChaenomeles speciosa fruit is a homologous medicine and food plant with a long history of multiple uses. It could be harvested near maturity and last for a long time. However, the optimal harvest strategy of Chaenomeles speciosa for various uses is currently unavailable. Here, untargeted metabolome at different harvest times during maturation was investigated for the first time, and 896 metabolites, including sugars, organic acids, amino acids, and phenylpropanoids, were identified. Optimal harvesting methods were proposed for different purposes. During the early maturation stages (before 105 days after full bloom), Ch. speciosa fruit could be harvested as Chinesemedicine. Whereas as snacks and food, Ch. speciosa fruit might be harvested at late maturity (after 120 days after full bloom). In addition, the overall network was revealed by integrating full-length Iso-seq and transcriptomics (RNA-seq) to investigate the association between quality-associated metabolites and Chaenomeles speciosa fruit gene expression during maturation. A few putative genes were captured via screening, dissecting and correlation analysis with the quality-associated metabolites (including d-glucose, catechin, gallocatechin, and succinic acid). Overall, in addition to providing a harvesting strategy for food and medicine, we also investigated the metabolism and gene expression pattern of Chaenomeles speciosa fruit during maturation. This comprehensive data and analyses laid the foundation for further investigating potential regulatory mechanisms during harvest and provided a new possibility for its development and utilization.PMID:36737903 | DOI:10.1016/j.foodres.2022.112314

Allergy Asthma Immunol Res. 2023 Feb 3. Online ahead of print.ABSTRACTPURPOSE: Obstructive sleep apnea (OSA), a highly prevalent and potentially serious sleep disorder, requires effective screening tools. Saliva is a useful biological fluid with various metabolites that might also influence upper airway patency by affecting surface tension in the upper airway. However, little is known about the composition and role of salivary metabolites in OSA. Therefore, we investigated the metabolomics signature in saliva from the OSA patients and evaluated the associations between identified metabolites and salivary surface tension.METHODS: We studied 68 subjects who visited sleep clinic due to the symptoms of OSA. All underwent full-night in-lab polysomnography. Patients with apnea-hypopnea index (AHI) < 10 were classified to the control, and those with AHI ≥ 10 were the OSA groups. Saliva samples were collected before and after sleep. The centrifuged saliva samples were analyzed by liquid chromatography with high-resolution mass spectrometry (ultra-performance liquid chromatography-tandem mass spectrometry; UPLC-MS/MS). Differentially expressed salivary metabolites were identified using open source software (XCMS) and Compound Discoverer 2.1. Metabolite set enrichment analysis (MSEA) was performed using MetaboAnalyst 5.0. The surface tension of the saliva samples was determined by the pendant drop method.RESULTS: Three human-derived metabolites (1-palmitoyl-2-[5-hydroxyl-8-oxo-6-octenoyl]-sn-glycerol-3-phosphatidylcholine [PHOOA-PC], 1-palmitoyl-2-[5-keto-8-oxo-6-octenoyl]-sn-glycerol-3-phosphatidylcholine [KPOO-PC], and 9-nitrooleate) were significantly upregulated in the after-sleep salivary samples from the OSA patients compared to the control group samples. Among the candidate metabolites, only PHOOA-PC was correlated with the AHI. In OSA samples, salivary surface tension decreased after sleep. The differences in surface tension were negatively correlated with PHOOA-PC and 9-nitrooleate concentrations. Furthermore, MSEA revealed that arachidonic acid-related metabolism pathways were upregulated in the after-sleep samples from the OSA group.CONCLUSIONS: This study revealed that salivary PHOOA-PC was correlated positively with the AHI and negatively with salivary surface tension in the OSA group. Salivary metabolomic analysis may improve our understanding of upper airway dynamics and provide new insights into novel biomarkers and therapeutic targets in OSA.PMID:37075797

Sci Rep. 2023 Feb 3;13(1):1989. doi: 10.1038/s41598-023-28966-6.ABSTRACTThe objective of this study was to investigate the impact of lactation stage and parity number on fatty acid and non-volatile polar metabolite profiles in sow colostrum and milk using a metabolomics approach. A total number of 63 colostrum, transient and mature milk were collected from primiparous and multiparous Landrace × Yorkshire crossbred sows. Macrochemical, fatty acid and non-volatile polar metabolite compositions of samples were analyzed using infrared spectrometry, gas chromatography coupled with mass-spectrometry and proton nuclear magnetic resonance spectroscopy, respectively. Univariate and multivariate statistical analysis demonstrated significant impacts of lactation stage and parity number on colostrum and milk compositions. Chemometric analysis revealed significant influences of sow parity on the distinction in fatty acid profiles of mature milk while the distinction in non-volatile polar metabolite profiles was more evident in colostrum. Alterations in the concentration of linoleic (C18:2n6), lignoceric (C24:0), behenic (C22:0), caprylic (C8:0) and myristoleic (C14:1) acid together with those of creatine, creatinine phosphate, glutamate and glycolate were statistically suggested to be mainly affected by sow parity number. Variations in the concentration of these compounds reflected the physiological function of sow mammary gland influenced. This information could be applied for feed and feeding strategies in lactating sows and improving lactating performances.PMID:36737492 | DOI:10.1038/s41598-023-28966-6

J Appl Microbiol. 2023 Feb 3:lxad019. doi: 10.1093/jambio/lxad019. Online ahead of print.ABSTRACTAIMS: Fusarium graminearum is a toxic fungus that affects food and feed crops. Piper sarmentosum extract (PSE) is a potential source of anti-mildew natural products for the food and feed industry due to its various pharmacological properties. In this study, we evaluated the antifungal activity and untargeted metabolomics analysis of PSE against F. graminearum.METHODS AND RESULTS: Antifungal activity was evaluated using the mycelium growth rate method. Untargeted metabolomics analysis of PSE was performed using ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results showed that PSE (1 and 2 mg ml-1) possesses inhibitory activity against F. graminearum, and a total of 17 compounds that including 8 alkaloids, 3 phenols, 3 lipids, and 3 organic acids might be the antifungal markers in PSE. Metabolomics analysis further revealed that PSE could significantly increase the levels of guanosine, guanine, adenosine, and L-isoleucine in fungi, which are related to purine and L-isoleucine metabolic pathways.CONCLUSIONS: PSE is a promising anti-mildew agent that inhibits the growth of F. graminearum in food and feed. PSE (1 and 2 mg ml-1) may exert antifungal properties by inhibiting fungal purine nucleotide synthesis and enhancing the level of L-isoleucine compared with the control groups.PMID:36737421 | DOI:10.1093/jambio/lxad019

Chem Biol Interact. 2023 Feb 1:110373. doi: 10.1016/j.cbi.2023.110373. Online ahead of print.ABSTRACTLung cancer is an aggressive malignancy and the leading cause of cancer-related deaths. Benzo [a]pyrene (B [a]P), a polycyclic hydrocarbon, plays a pivotal role in lung carcinogenesis. Uncovering the molecular mechanism underlying the pathophysiology of B [a]P-induced malignancy is crucial. Male Sprague Dawley rats were induced with B [a]P to generate a lung cancer model. The B [a]P-administered rats show increased body and lung weight, loss of normal pulmonary architecture, and decreased survival. This study demonstrated that B [a]P upregulates activating transcription factor-6 (ATF6) and C/EBP Homologous Protein (CHOP) and induces endoplasmic reticulum (ER) stress. B [a]P also dysregulated mitochondrial homeostasis by upregulating, PTEN-induced putative kinase-1 (PINK1) and Parkin. B [a]P affected the levels of superoxide dismutase (SOD), reduced glutathione (GSH), malondialdehyde (MDA), and increased oxidative stress. B [a]P exposure downregulated Kelch-like ECH-associated protein 1 (Keap1) and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1(HO1). The metabolomic study identified that biosynthesis of nucleotide, amino acids, pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA), and glutathione metabolism were up-accumulated. On the other hand, lower accumulation of fatty acids e.g., palmitic acid, stearic acid, and oleic acid were reported in the B [a]P induced group. Overall, the results of this study indicate that B [a]P treatment affects several signaling and metabolic pathways, whose dysregulation might be involved in lung cancer induction.PMID:36736873 | DOI:10.1016/j.cbi.2023.110373

Environ Res. 2023 Feb 1:115376. doi: 10.1016/j.envres.2023.115376. Online ahead of print.ABSTRACTCadmium (Cd) and chromium (Cr) are widespread contaminants with a high risk to the environment and humans. Herein we isolated a novel strain of Serratia marcescens, namely strain S27, from soil co-contaminated with Cd and Cr. This strain showed strong resistance to Cd as well as Cr. S27 cells demonstrated Cd adsorption rate of 45.8% and Cr reduction capacity of 84.4% under optimal growth conditions (i.e., 30 °C, 200 rpm, and pH 7.5). Microscopic characterization of S27 cells revealed the importance of the functional groups C-O-C, C-H-O, C-C, C-H, and -OH, and also indicated that Cr reduction occurred on bacterial cell membrane. Cd(II) and Cr(VI) bioaccumulation on S27 cell surface was mainly in the form of Cd(OH)2 and Cr2O3, respectively. Further, metabolomic analyses revealed that N-arachidonoyl-l-alanine was the key metabolite that promoted Cd and Cr complexation by S27; it primarily promotes γ-linolenic acid (GLA) metabolism, producing siderophores and coordinating with organic acids to enhance metal bioavailability. To summarize, our results suggest that S27 is promising for the bioremediation of environments contaminated with Cd and Cr in tropical regions.PMID:36736755 | DOI:10.1016/j.envres.2023.115376

J Lipid Res. 2023 Jan 31:100338. doi: 10.1016/j.jlr.2023.100338. Online ahead of print.ABSTRACTPathogenic mechanisms in degenerative thoracic aortic aneurysms (TAA) are still unclear. There is an ongoing debate about whether TAAs are caused by uniform or distinct processes, which would obviously have a major impact on future treatment strategies. Clearly, the ultimate outcome of TAA subgroups associated with a tricuspid aortic valve (TAV) or a bicuspid aortic valve (BAV) is the same, namely a TAA. Based on results from our own and others' studies, we decided to compare the different TAAs (TAV and BAV) and controls using a broad array of analyses, i.e. metabolomic analyses, gene expression profiling, protein expression analyses, histological characterization, and MALDI imaging. Central findings of the present study are the presence of non-canonical atherosclerosis, pathological accumulation of macrophages and disturbances of lipid metabolism in the aortic media. Moreover, we have also found that lipid metabolism is impaired systemically. Importantly, all of the above described phenotypes are characteristic for TAV-TAA only, and not for BAV-TAA. In summary, our results suggest different modes of pathogenesis in TAV- and BAV-associated aneurysms. Intimal atherosclerotic changes play a more central role in TAV-TAA formation than previously thought, particularly as the observed alterations do not follow classical patterns. Atherosclerotic alterations are not limited to the intima, but also affect and alter the TAV-TAAs media. Further studies are needed to i) clarify patho-relevant intima-media interconnections, ii) define the origin of the systemic alteration of lipid metabolism, and iii) to define valid biomarkers for early diagnosis, disease progression and successful treatments in TAV-TAAs.PMID:36736622 | DOI:10.1016/j.jlr.2023.100338

Neuroscience. 2023 Jan 31:S0306-4522(23)00047-7. doi: 10.1016/j.neuroscience.2023.01.029. Online ahead of print.ABSTRACTIn Mild Cognitive Impairment (MCI), identifying a high risk of conversion to Alzheimer's Disease Dementia (AD) is a primary goal for patient management. Machine Learning (ML) algorithms are widely employed to pursue data-driven diagnostic and prognostic goals. An agreement on the stability of these algorithms -when applied to different biomarkers and other conditions- is far from being reached. In this study, we compared the different prognostic performances of three supervised ML algorithms fed with multimodal biomarkers of MCI subjects obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Random Forest, Gradient Boosting, and eXtreme Gradient Boosting algorithms predict MCI conversion to AD. They can also be simultaneously employed -with the voting procedure- to improve predictivity. AD prediction accuracy is influenced by the nature of the data (i.e., neuropsychological test scores, cerebrospinal fluid AD-related proteins and APOE ε4, cerebral structural MRI (sMRI) data). In our study, independent of the applied ML algorithms, sMRI data showed the lowest accuracy (0.79) compared to other classes. Multimodal data were helpful in the algorithms' performances by combining clinical and biological measures. Accordingly, using the three ML algorithms, the highest accuracy (0.90) was reached by employing neuropsychological and AD-related biomarkers. Finally, the feature selection procedure indicated that the most critical variables in the respective classes were the ADAS-Cog-13 scale, the medial temporal lobe and hippocampus atrophy, and the ratio between phosphorylated Tau and Aβ42 proteins. In conclusion, our data support the notion that using multiple ML algorithms and multimodal biomarkers helps make more accurate and solid predictions.PMID:36736612 | DOI:10.1016/j.neuroscience.2023.01.029

Environ Pollut. 2023 Jan 31:121171. doi: 10.1016/j.envpol.2023.121171. Online ahead of print.ABSTRACTThis study evaluated the responses of cell density, photosynthesis activity, dry cell weight, lipid productivity, proteome and metabolome in two non-toxic cyanobacterial species (Synechococcus sp. and Chroococcus sp.) exposed to two frequently detected antibiotics (sulfamethoxazole and ofloxacin) at test concentrations of 0.2-20.0 μg L-1 in a 4-day culture period. Upregulated antioxidant enzymes and oxidoreductases contributed to antibiotic biodegradation in Synechococcus sp.; whereas, upregulated carotenoid protein contributed to antibiotic biodegradation in Chroococcus sp. The 4-day removal efficiencies of sulfamethoxazole and ofloxacin by cyanobacteria were 35.98-66.23% and 33.01-61.92%, respectively. In cyanobacteria, each antibiotic induced hormetic responses, such as increase in cell density, dry cell weight, and photosynthetic activity; upregulation of photosynthesis-related proteins; and elevation of lipid expression by up to 2.05-fold. Under antibiotic stress, the two cyanobacterial species preferred to store energy in the form of lipids rather than ATP, with fructose-bisphosphate aldolase playing an essential role in lipid synthesis. The downregulation of lipid transporters also facilitated lipid accumulation in Synechococcus sp. In general, the two non-toxic cyanobacterial species achieved a good combination of lipid deposition and antibiotic treatment performance, especially in Chroococcus sp. exposed to sulfamethoxazole.PMID:36736559 | DOI:10.1016/j.envpol.2023.121171

J Biol Chem. 2023 Jan 31:102960. doi: 10.1016/j.jbc.2023.102960. Online ahead of print.ABSTRACTEarly diabetic kidney disease (DKD) is marked by dramatic metabolic reprogramming due to nutrient excess, mitochondrial dysfunction, and increased renal energy requirements from hyperfiltration. We hypothesized that changes in metabolism in DKD may be regulated by Sirtuin 5 (SIRT5), a deacylase that removes post-translational modifications derived from acyl-coenzyme A and has been demonstrated to regulate numerous metabolic pathways. We found decreased malonylation in the kidney cortex (∼80% proximal tubules) of type 2 diabetic BKS db/db mice, associated with increased SIRT5 expression. We performed a proteomics analysis of malonylated peptides and found that proteins with significantly decreased malonylated lysines in the db/db cortex were enriched in non-mitochondrial metabolic pathways: glycolysis and peroxisomal fatty acid oxidation (FAO). To confirm relevance of these findings in human disease, we analyzed diabetic kidney transcriptomic data from a cohort of Southwestern American Indians which revealed a tubulointerstitial-specific increase in Sirt5 expression. These data were further corroborated by immunofluorescence data of SIRT5 from non-diabetic and DKD cohorts. Furthermore, overexpression of SIRT5 in cultured human proximal tubules demonstrated increased aerobic glycolysis. Conversely, we observed reduced glycolysis with decreased SIRT5 expression. These findings suggest that SIRT5 may lead to differential nutrient partitioning and utilization in DKD. Taken together, our findings highlight a previously unrecognized role for SIRT5 in metabolic reprogramming in DKD.PMID:36736426 | DOI:10.1016/j.jbc.2023.102960

Immunity. 2023 Jan 24:S1074-7613(23)00018-3. doi: 10.1016/j.immuni.2023.01.008. Online ahead of print.ABSTRACTGaucher disease (GD) is the most common lysosomal storage disease caused by recessive mutations in the degrading enzyme of β-glucosylceramide (β-GlcCer). However, it remains unclear how β-GlcCer causes severe neuronopathic symptoms, which are not fully treated by current therapies. We herein found that β-GlcCer accumulating in GD activated microglia through macrophage-inducible C-type lectin (Mincle) to induce phagocytosis of living neurons, which exacerbated Gaucher symptoms. This process was augmented by tumor necrosis factor (TNF) secreted from activated microglia that sensitized neurons for phagocytosis. This characteristic pathology was also observed in human neuronopathic GD. Blockade of these pathways in mice with a combination of FDA-approved drugs, minocycline (microglia activation inhibitor) and etanercept (TNF blocker), effectively protected neurons and ameliorated neuronopathic symptoms. In this study, we propose that limiting unrestrained microglia activation using drug repurposing provides a quickly applicable therapeutic option for fatal neuronopathic GD.PMID:36736320 | DOI:10.1016/j.immuni.2023.01.008

Aquat Toxicol. 2023 Jan 20;256:106401. doi: 10.1016/j.aquatox.2023.106401. Online ahead of print.ABSTRACTTris(2-butoxy) ethyl phosphate (TBOEP) is a typical organophosphorus flame retardant (OPFR), which has been detected in natural water bodies and drinking water and has reached a certain concentration. As a new type of organic pollutant, the environmental health risk of TBOEP needs to be assessed urgently. Here, Caenorhabditis elegans were exposed to 0, 50, 500, and 5000 ng/L TBOEP in water for 72 h. The results showed that TBOEP exposure caused concentration-dependent inhibition to the growth of nematodes, while exposure to 5000 ng/L TBOEP significantly inhibited the locomotor behavior of nematodes. Transcriptomic and metabolomic analysis showed that the disturbances in neurotransmitter transmission and amino acid, carbohydrate, and lipid metabolism were the reason for the neurotoxicity and growth toxicity of TBOEP to nematodes. These results provide basic data and a theoretical basis for evaluating the environmental health risks of organophosphorus flame retardants.PMID:36736151 | DOI:10.1016/j.aquatox.2023.106401

Spectrochim Acta A Mol Biomol Spectrosc. 2023 Jan 20;292:122394. doi: 10.1016/j.saa.2023.122394. Online ahead of print.ABSTRACTReliable origin certification methods are essential for the protection of high-value genuine medicinal material with designated origins and geographical indication (GI) products. Aconiti Lateralis Radix Praeparata (Fuzi), one well-known traditional Chinese medicine and geographical indication products have remarkable efficacy and wide clinical application, with high demand in domestic and international markets. The efficacy and price of Fuzi from different origins vary, and it is difficult for the general public to accurately identify them through traditional experience. The mass spectrometry detection technology based on the plant metabolomics is tedious and lengthy in test sample preparation, complicated in operation, long in detection time, and low in reproducibility. As a sophisticated, green, fast, and low-loss detection technique, infrared spectroscopy is integrated by machine learning to bring new ways for quality regulation and control of traditional Chinese medicines. An analytical method based on mid-infrared spectroscopy combined with a random forest algorithm was developed to verify the geographical origin of authentic herbs and/or GI products. The method successfully predicted and classified three varieties of Chinese GI Fuzi and four varieties of non-GI Fuzi. In this study, an environment-friendly traceability strategy with fast analysis, low sample loss and high precision was used to provide a new strategy for identifying the origin of Fuzi.PMID:36736047 | DOI:10.1016/j.saa.2023.122394

Semin Arthritis Rheum. 2023 Jan 13;59:152163. doi: 10.1016/j.semarthrit.2023.152163. Online ahead of print.ABSTRACTPURPOSE: Osteoarthritis (OA) is a joint disease that is clinically diagnosed using components of history, physical exam, and characteristic radiographic findings, such as joint space narrowing. Currently, there are no laboratory findings that are specific to a diagnosis of OA. The purpose of this systematic review is to evaluate the state of current studies of metabolomic biomarkers that can aid in the diagnosis and treatment of OA.METHODS: Articles were gathered from PubMed and Web of Science using the search terms "osteoarthritis" and "biomarkers" and "metabolomics". Last search of databases took place December 3rd, 2022. Duplicates were manually screened, along with any other results that were not original journal articles. Only original reports involving populations with diagnosed primary or secondary OA (human participants) or surgically induced OA (animal participants) and a healthy control group for comparison were considered for inclusion. Metabolites and metabolic pathways reported in included articles were then manually extracted and evaluated for importance based on reported a priori p-values and/or area under the receiver-operator curve (AUC).RESULTS: Of the 161 results that were returned in the database searches, 43 unique articles met the inclusion criteria. Articles were categorized based on body fluid analyzed: 6 studies on urine samples, 13 studies on plasma samples, 11 studies on synovial fluid (SF) samples, 11 studies on serum samples, 1 study on both synovial fluid and serum, and 1 study that involved both plasma and synovial fluid. To synthesize results, individual metabolites, as well as metabolic pathways that involve frequently reported metabolites, are presented for each study. Indications as to whether metabolite levels were increased or decreased are also included if this data was included in the original articles.CONCLUSIONS: These studies clearly show that there are a wide range of metabolic pathways perturbed in OA. For this period, there was no consensus on a single metabolite, or panel of metabolites, that would be clinically useful in early diagnosis of OA or distinguishing OA from a healthy control. However, many common metabolic pathways were identified in the studies, including TCA cycle, fatty acid metabolism, amino acid metabolism (notably BCAA metabolism and tryptophan metabolism via kynurenine pathway), nucleotide metabolism, urea cycle, cartilage matrix components, and phospholipid metabolism. Future research is needed to define effective clinical biomarkers of osteoarthritis from metabolomic and other data.PMID:36736024 | DOI:10.1016/j.semarthrit.2023.152163

Sci Adv. 2023 Feb 3;9(5):eadd0455. doi: 10.1126/sciadv.add0455. Epub 2023 Feb 3.ABSTRACTSkeletal muscle myofibers are heterogeneous in their metabolism. However, metabolomic profiling of single myofibers has remained difficult. Mass spectrometry imaging (MSI) is a powerful tool for imaging molecular distributions. In this work, we optimized the workflow of matrix-assisted laser desorption/ionization (MALDI)-based MSI from cryosectioning to metabolomics data analysis to perform high-spatial resolution metabolomic profiling of slow- and fast-twitch myofibers. Combining the advantages of MSI and liquid chromatography-MS (LC-MS), we produced spatial metabolomics results that were more reliable. After the combination of high-spatial resolution MSI and LC-MS metabolomic analysis, we also discovered a new subtype of superfast type 2B myofibers that were enriched for fatty acid oxidative metabolism. Our technological workflow could serve as an engine for metabolomics discoveries, and our approach has the potential to provide critical insights into the metabolic heterogeneity and pathways that underlie fundamental biological processes and disease states.PMID:36735792 | DOI:10.1126/sciadv.add0455

PLoS Pathog. 2023 Feb 3;19(2):e1011126. doi: 10.1371/journal.ppat.1011126. Online ahead of print.ABSTRACTFoot-and-mouth disease, a class of animal diseases, is caused by foot-and-mouth disease virus (FMDV). The metabolic changes during FMDV infection remain unclear. Here, PK-15 cells, serum, and tonsils infected with FMDV were analyzed by metabolomics. A total of 284 metabolites in cells were significantly changed after FMDV infection, and most of them belong to amino acids and nucleotides. Further studies showed that FMDV infection significantly enhanced aspartate in vitro and in vivo. The amino acid transporter solute carrier family 38 member 8 (SLC38A8) was responsible for FMDV-upregulated aspartate. Enterovirus 71 (EV71) and Seneca Valley virus (SVV) infection also enhanced aspartate by SLC38A8. Aspartate aminotransferase activity was also elevated in FMDV-, EV71-, and SVV-infected cells, which may lead to reversible transition between the TCA cycle and amino acids synthesis. Aspartate and SLC38A8 were essential for FMDV, EV71, and SVV replication in cells. In addition, aspartate and SLC38A8 also promoted FMDV and EV71 replication in mice. Detailed analysis indicated that FMDV infection promoted the transfer of mTOR to lysosome to enhance interaction between mTOR and Rheb, and activated PI3K/AKT/TSC2/Rheb/mTOR/p70S6K1 pathway to promote viral replication. The mTORC1 signaling pathway was responsible for FMDV-induced SLC38A8 protein expression. For the first time, our data identified metabolic changes during FMDV infection. These data identified a novel mechanism used by FMDV to upregulate aspartate to promote viral replication and will provide new perspectives for developing new preventive strategies.PMID:36735752 | DOI:10.1371/journal.ppat.1011126

PLoS One. 2023 Feb 3;18(2):e0274060. doi: 10.1371/journal.pone.0274060. eCollection 2023.ABSTRACTOBJECTIVES: To evaluate the association between plasma metabolites, biochemical analytes, diagnostic imaging findings, and the histologic diagnosis of hepatic lipidosis in bearded dragons. To assess the effects of gemfibrozil therapy on hepatic lipid accumulation and associated diagnostic tests.ANIMALS: Fourteen bearded dragons (Pogona vitticeps) with varying severity of hepatic lipid accumulation (with and without hepatic lipidosis) were included.PROCEDURES: Animals underwent coelomic ultrasound, computed tomography (CT) scans, and coelioscopic hepatic biopsies. Clinical pathology tests included lipidologic tests, hepatic biomarkers, and mass spectrometry-based metabolomics. Animals were medicated with gemfibrozil 6mg/kg orally once a day for 2 months in a randomized blinded clinical trial prior to repeating previous diagnostic testing.RESULTS: Hounsfield units on CT were negatively associated with increased hepatic vacuolation, while ultrasound and gross evaluation of the liver were not reliable. Beta-hydroxybutyric-acid (BHBA) concentrations were significantly associated with hepatic lipidosis. Metabolomics and lipidomics data found BHBA and succinic acid to be potential biomarkers for diagnosing hepatic lipidosis in bearded dragons. Succinic acid concentrations were significantly lower in the gemfibrozil treatment group. There was a tendency for improvement in the biomarkers and reduced hepatic fat in bearded dragons with hepatic lipidosis when treated with gemfibrozil, though the improvement was not statistically significant.CONCLUSIONS: These findings provide information on the antemortem assessment of hepatic lipidosis in bearded dragons and paves the way for further research in diagnosis and treatment of this disease.PMID:36735707 | DOI:10.1371/journal.pone.0274060