PubMed

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

Rapid Commun Mass Spectrom. 2023 Feb 3:e9486. doi: 10.1002/rcm.9486. Online ahead of print.ABSTRACTRATIONALE: Proteins extracted from archaeological bone and teeth are utilised for investigating the phylogeny of extinct and extant species, the biological sex and age of past individuals, as well as ancient health and physiology. However, variable preservation of proteins in archaeological materials represents a major challenge.METHODS: In order to better understand the spatial distribution of ancient proteins preserved within teeth, we apply Matrix Assisted Laser Desorption/Ionisation Mass Spectrometry Imaging (MALDI-MSI) for the first time to bioarchaeological samples to visualise the intensity of proteins in archaeological teeth thin sections. We specifically explore the spatial distribution of four proteins (collagen type I, of which chains alpha -1 and 2, alpha-2-HS-glycoprotein, haemoglobin subunit alpha and myosin light polypeptide 6).RESULTS: We successfully identify ancient proteins in archaeological teeth thin sections using mass spectrometry imaging. The data are available via ProteomeXchange with identifier PXD038114. However, we observe that peptides did not always follow our hypotheses for their spatial distribution, with distinct differences observed in the spatial distribution of several proteins, and occasionally between peptides of the same protein.CONCLUSIONS: While it remains unclear what causes these differences in protein intensity distribution within teeth, as revealed by MALDI-MSI in this study, we demonstrate that MALDI-MSI can be successfully applied to mineralised bioarchaeological tissues to detect ancient peptides. In future applications, this technique could be particularly fruitful not just for understanding the preservation of proteins in a range of archaeological materials, but making informed decisions on sampling strategies and the targeting of key proteins of archaeological and biological interest.PMID:36735645 | DOI:10.1002/rcm.9486

Clin J Am Soc Nephrol. 2023 Jan 13. doi: 10.2215/CJN.0000000000000062. Online ahead of print.ABSTRACTBACKGROUND: High ultra-processed food consumption is associated with higher risk of CKD. However, there is no biomarker for ultra-processed food, and the mechanism through which ultra-processed food is associated with CKD is not clear. Metabolomics can provide objective biomarkers of ultra-processed food and provide important insights into the mechanisms by which ultra-processed food is associated with risk of incident CKD. Our objective was to identify serum metabolites associated with ultra-processed food consumption and investigate whether ultra-processed food-associated metabolites are prospectively associated with incident CKD.METHODS: We used data from 3751 Black and White men and women (aged 45-64 years) in the Atherosclerosis Risk in Communities study. Dietary intake was assessed using a semiquantitative 66-item food frequency questionnaire, and ultra-processed food was classified using the NOVA classification system. Multivariable linear regression models were used to identify the association between 359 metabolites and ultra-processed food consumption. Cox proportional hazards models were used to investigate the prospective association of ultra-processed food-associated metabolites with incident CKD.RESULTS: Twelve metabolites (saccharine, homostachydrine, stachydrine, N2, N2-dimethylguanosine, catechol sulfate, caffeine, 3-methyl-2-oxovalerate, theobromine, docosahexaenoate, glucose, mannose, and bradykinin) were significantly associated with ultra-processed food consumption after controlling for false discovery rate <0.05 and adjusting for sociodemographic factors, health behaviors, eGFR, and total energy intake. The 12 ultra-processed food-related metabolites significantly improved the prediction of ultra-processed food consumption (difference in C statistics: 0.069, P<1×10-16). Higher levels of mannose, glucose, and N2, N2-dimethylguanosine were associated with higher risk of incident CKD after a median follow-up of 23 years.CONCLUSIONS: We identified 12 serum metabolites associated with ultra-processed food consumption and three of them were positively associated with incident CKD. Mannose and N2, N2-dimethylguanosine are novel markers of CKD that may explain observed associations between ultra-processed food and CKD.PMID:36735499 | DOI:10.2215/CJN.0000000000000062

Anal Chem. 2023 Feb 3. doi: 10.1021/acs.analchem.2c04231. Online ahead of print.ABSTRACTAccurate reconstruction of metabolic pathways is an important prerequisite for interpreting metabolomics changes and understanding the diverse biological processes in disease models. A tracer-based metabolomics strategy utilizes stable isotope-labeled precursors to resolve complex pathways by tracing the labeled atom(s) to downstream metabolites through enzymatic reactions. Isotope enrichment analysis is informative and achieved by counting total labeled atoms and acquiring the mass isotopologue distribution (MID) of the intact metabolite. However, quantitative analysis of labeled metabolite substructures/moieties (MS2 fragments) can offer more valuable insights into the reaction connections through measuring metabolite transformation. In order to acquire the isotopic labeling information at the intact metabolite and moiety level simultaneously, we developed a method that couples hydrophilic interaction liquid chromatography (HILIC) with Zeno trap-enabled high-resolution multiple reaction monitoring (MRMHR). The method enabled accurate and reproducible MID quantification for intact metabolites as well as their fragmented moieties, with notably high sensitivity in the MS2 fragmentation mode based on the measurement of 13C- or 15N-labeled cellular samples. The method was applied to human-induced pluripotent stem cell-derived neurons to trace the fate of 13C/15N atoms from D-13C6-glucose/L-15N2-glutamine added to the media. With the MID analysis of both intact metabolites and fragmented moieties, we validated the pathway reconstruction of de novo glutathione synthesis in mid-brain neurons. We discovered increased glutathione oxidization from both basal and newly synthesized glutathione pools under neuronal oxidative stress. Furthermore, the significantly decreased de novo glutathione synthesis was investigated and associated with altered activities of several key enzymes, as evidenced by suppressed glutamate supply via glucose metabolism and a diminished flux of glutathione synthetic reaction in the neuronal model of rotenone-induced neurodegeneration.PMID:36735349 | DOI:10.1021/acs.analchem.2c04231

J Mater Chem B. 2023 Feb 3. doi: 10.1039/d2tb02756a. Online ahead of print.ABSTRACTDue to their excellent antibacterial ability, silver nanomaterials (Ag NMs) are the most frequently used nanomaterials. Their widespread use introduces the risk of human ingestion. However, the potential toxicity of Ag NMs to the gut microbiota and their metabolic profile are yet to be fully explored. In this study, we examined the effects of Ag NMs after oral administration (0.5 mg kg-1 and 2.5 mg kg-1, 14 and 28 days) on gut homeostasis by integrating tissue imaging, 16s rRNA gene sequencing and metabolomics techniques. We uncovered that silver nanoparticles (Ag NPs) and silver nanowires (Ag NWs) altered the structure (inhibiting the proliferation of Gram-negative bacteria) and decreased the diversity of gut microbiota in mice after short-term (14 days) exposure, while the microbial community tended to recover after long-term exposure (28 days), indicating that the resistance and resilience of the gut microbiome may pose a defense against the interference by reactive, exogenous nanomaterials. Interestingly, even though the gut microbiota structure recovered after 28 days of exposure, the gut metabolites significantly changed, showing increased 1H-indole-3-carboxylic acid and elevated levels of 5-HT in the gut and blood. Collectively, our results provide a piece of evidence on the association between the ingestion of exogenous nanoparticles and gut homeostasis, especially the metabolic profile of the host. This work thus provides additional insights for the continued investigation of the adverse effects of silver nanomaterials on biological hosts.PMID:36734837 | DOI:10.1039/d2tb02756a

Food Funct. 2023 Feb 3. doi: 10.1039/d2fo03054c. Online ahead of print.ABSTRACTNon-alcoholic steatohepatitis (NASH) is a chronic liver disease with few therapeutic options available currently. Hemp seed oil extracted from the seeds of hemp (Cannabis sativa L.) has significant nutritional and biological properties due to the unique composition of polyunsaturated fatty acids and various antioxidant compounds. However, little is known about the beneficial effects and molecular mechanisms of hemp seed oil on NASH. Here, the hepatoprotective effects of hemp seed oil on methionine-choline-deficient (MCD) diet-induced NASH in C57BL/6 mice were explored via integration of transcriptomics and metabolomics. Hemp seed oil could improve hepatic steatosis, inflammation and fibrosis in mice with MCD diet-induced NASH. In a nuclear magnetic resonance (NMR)-based metabonomic study, the hepatic and urinary metabolic profiles of mice supplemented with hemp seed oil showed a tendency to recover to healthy controls compared to those of NASH mice. Eight potential biomarkers associated with NASH in both liver tissue and urine were restored to near normal levels by administration of hemp seed oil. The proposed pathways were mainly involved in pyrimidine metabolism, one-carbon metabolism, amino acid metabolism, glycolysis and the tricarboxylic acid (TCA) cycle. Hepatic transcriptomics based on Illumina RNA-Seq sequencing showed that hemp seed oil exerted anti-NASH activities by regulating multiple signaling pathways, e.g., downregulation of the TNF signaling pathway, the IL-17 signaling pathway, the MAPK signaling pathway and the NF-κB signaling pathway, which played a pivotal role in the pathogenesis of NASH. In particular, integration of metabonomic and transcriptomic results suggested that hemp seed oil could attenuate NASH-related liver fibrosis by inhibition of glutaminolysis. These results provided new insights into the hepatoprotective effects of hemp seed oil against MCD diet-induced NASH and hemp seed oil might have potential as an effective therapy for NASH.PMID:36734470 | DOI:10.1039/d2fo03054c

Chembiochem. 2023 Feb 3. doi: 10.1002/cbic.202200802. Online ahead of print.ABSTRACTThe emergence of drug resistant pathogens necessitates development of new countermeasures. In this regard, the introduction of probiotics to directly attack or competitively exclude pathogens presents a useful strategy. Application of this approach requires an understanding of how a probiotic and its target pathogen interact. A key means of probiotic-pathogen interaction involves the production of small molecules called natural products (NPs). Here, we report use of whole-cell matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry for characterization of NP production by candidate probiotics (mouse airway microbiome isolates) when co-cultured with respiratory pathogen Burkholderia. We found that a Bacillus velezensis strain inhibits growth of and elicits NP production by B. thailandensis. Dereplication of known NPs detected in the metabolome of this B. velezensis strain suggests that a previously unannotated bioactive compound is involved. Thus, we present use of whole-cell MALDI as a broadly applicable method for screening of NP composition of microbial co-cultures, which can be combined with other -omics methods for characterization of probiotic-pathogen, and other microbe-microbe, interactions.PMID:36734186 | DOI:10.1002/cbic.202200802

J Anim Sci. 2023 Feb 3:skad039. doi: 10.1093/jas/skad039. Online ahead of print.ABSTRACTInappropriate dietary management may lead to delayed recovery from castration surgery and significant weight gain in cats after castration. Wet canned food often exhibits more advantageous characteristics than dry food (e.g., higher palatability and digestibility, and lower energy density). This study compared the effects of canned and dry food on surgical recovery and weight management in cats after castration. Eighteen healthy cats (weighed 4.33 ± 1.04 kg and aged 18-months old) were allocated to one of the two dietary treatments (N = 9/group), dry (CON) and canned food (CAN) balanced for sex and initial BW. Cats were fed ad libitum for 7 weeks, including one week before surgery (week 0) and 6 weeks after surgery (week 1 to 6). Daily dry matter intake (DMI), and weekly body weight (BW) and body condition score (BCS) was obtained. Feces were collected for measuring nutrient digestibility and concentrations of short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA). Physical pain and wound surface assessment were performed at week 1. Blood was also collected intermittently for measuring biochemical indices and untargeted metabolomics analysis. Results indicated that BW, BCS and daily DMI in CON group increased (P < 0.05) over time after castration, but were maintained relatively stable in CAN group. Cats in CAN group exhibited less pain-related behavior as reflected by lower score of comfort (P < 0.05) and vocalization (P < 0.10), improved wound surface assessment (P < 0.10), lower level of lipase (P < 0.10) and ratio of blood urea nitrogen/serum creatinine (BUN/SC; P < 0.05), and higher level of superoxide dismutase (SOD; P < 0.05) in week 1 than CON cats. Meanwhile, the CAN group had significantly higher concentration of immunoglobulin G (IgG) on day 5 and 7, and higher level of high-density lipoprotein cholesterol (HDL-C; P < 0.10) but lower triglyceride (TG; P < 0.05) than CON group on day 20 and 48. Fecal total and most individual SCFA increased significantly from week 1 to week 6 regardless of diet, but the increase of butyric acid over time only occurred in CON group (P < 0.05). Also, serum metabolomic analysis revealed differential metabolic pathways between the two groups. Overall, compared with the dry food, the canned food tested in our study promoted cat wound recovery by reducing pain and increasing immune and antioxidative capacity after sterilizing surgery, and helped to maintain healthy body condition in cats after castration.PMID:36734030 | DOI:10.1093/jas/skad039

Front Cardiovasc Med. 2023 Jan 17;9:1074257. doi: 10.3389/fcvm.2022.1074257. eCollection 2022.ABSTRACTBACKGROUND/AIMS: The effect and underlying mechanism of microgravity on myocardium still poorly understood. The present study aims to reveal the effect and underlying mechanism of tail-suspension-induced microgravity on myocardium of rats.METHODS: Tail-suspension was conducted to simulate microgravity in rats. Echocardiography assay was used to detect cardiac function. The cardiac weight index was measured. Hematoxylin and eosin (HE) staining and transmission electron microscopy assay were conducted to observe the structure of the tissues. RNA sequencing and non-targeted metabolomics was employed to obtain transcriptome and metabolic signatures of heart from tail-suspension-induced microgravity and control rats.RESULTS: Microgravity induced myocardial atrophy and decreased cardiac function in rats. Structure and ultrastructure changes were observed in myocardium of rats stimulated with microgravity. RNA sequencing for protein coding genes was performed and identified a total of 605 genes were differentially expressed in myocardium of rats with tail suspension, with 250 upregulated and 355 downregulated (P < 0.05 and | log2fold change| > 1). A total of 55 differentially expressed metabolites were identified between the two groups (VIP > 1 and P < 0.05) by the metabolic profiles of heart tissues from microgravity groups and control. Several major pathways altered aberrantly at both transcriptional and metabolic levels, including FoxO signaling pathway, Amyotrophic lateral sclerosis, Histidine metabolism, Arginine and proline metabolism.CONCLUSION: Microgravity can induce myocardial atrophy and decreases cardiac function in rats and the molecular alterations at the metabolic and transcriptomic levels was observed, which indicated major altered pathways in rats with tail suspension. The differentially expressed genes and metabolites-involved in the pathways maybe potential biomarkers for microgravity-induced myocardial atrophy.PMID:36733828 | PMC:PMC9886666 | DOI:10.3389/fcvm.2022.1074257

Anim Nutr. 2022 Dec 7;12:375-387. doi: 10.1016/j.aninu.2022.12.004. eCollection 2023 Mar.ABSTRACTIn order to find viable alternative protein sources for aquaculture, we evaluated the effect of partial or complete replacement of dietary soybean meal with yellow mealworm (TM) on the flesh quality of grass carp. In this study, 180 grass carp (511.85 ± 0.25 g) were fed 3 experimental diets in which 0% (CN), 30% (YM30) and 100% (YM100) dietary soybean meal was replaced by TM for 90 d. The results showed that growth performance, biological parameters and serum antioxidant capacity of grass carp were not affected by dietary TM (P > 0.05). Both muscle and whole body crude protein were obviously promoted with the increase of dietary TM (P < 0.05), and the concentration of heavy metal in muscle was not influenced (P > 0.05), indicating that food safety was not influenced by TM. Dietary TM improved muscle textural characteristics by elevating adhesiveness, springiness and chewiness in YM100 (P < 0.05). In addition, the muscle tenderness was significantly increased by declining the shear force (P < 0.05). The muscle fiber density in YM30 &YM100 and length of dark bands and sarcomeres in YM100 were obviously increased (P < 0.05). The expression of myf5, myog and myhc exhibited a significant upward trend with the increase of dietary TM (P < 0.05), which promoted fiber density, length of sarcomere and texture of grass carp muscle. According to the results of metabolomics, the arachidonate (ARA) and eicosapentaenoic acid (EPA) were notably elevated in YM30 and YM100, which indicated that the improvement of flesh quality of grass carp may contribute to the dietary TM influence on muscle lipid metabolism, especially the polyunsaturated fatty acids. In conclusion, TM can completely replace dietary soybean meal and improve the nutritional value of grass carp.PMID:36733784 | PMC:PMC9883186 | DOI:10.1016/j.aninu.2022.12.004