PubMed

Nat Chem. 2024 Jul 30. doi: 10.1038/s41557-024-01577-y. Online ahead of print.ABSTRACTThe identification of readers, an important class of proteins that recognize modified residues at specific sites, is essential to uncover the biological roles of post-translational modifications. Photoreactive crosslinkers are powerful tools for investigating readers. However, existing methods usually employ synthetically challenging photoreactive warheads, and their high-energy intermediates generated upon irradiation, such as nitrene and carbene, may cause substantial non-specific crosslinking. Here we report dimethylsulfonium as a methyllysine mimic that binds to specific readers and subsequently crosslinks to a conserved tryptophan inside the binding pocket through single-electron transfer under ultraviolet irradiation. The crosslinking relies on a protein-templated σ-π electron donor-acceptor interaction between sulfonium and indole, ensuring excellent site selectivity for tryptophan in the active site and orthogonality to other methyllysine readers. This method could escalate the discovery of methyllysine readers from complex cell samples. Furthermore, this photo crosslinking strategy could be extended to develop other types of microenvironment-dependent conjugations to site-specific tryptophan.PMID:39079947 | DOI:10.1038/s41557-024-01577-y

Phytother Res. 2024 Jul 30. doi: 10.1002/ptr.8271. Online ahead of print.ABSTRACTMagnoflorine (Mag), a natural alkaloid component originating from the Ranunculaceae Juss. Family, has a various of pharmacological activities. This study aimed to investigate the therapeutic effects and potential mechanism of Mag on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) based on comprehensive approaches. Therapeutic effects of Mag on 3% DSS-induced UC mice were analyzed. UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway of Mag on DSS-induced UC. Furthermore, the predicted mRNA and protein levels of JAK2/STAT3 signaling pathway in colon tissue were verified and assessed by qRT-PCR and Western Blotting, respectively. Therapeutic effects of Mag on UC mice were presented in down-regulation serum biochemical indices, alleviating histological damage of colon tissue. Serum untargeted metabolomics analysis showed that the potential mechanism of Mag on UC is mainly associated with the regulation of six biomarkers and 11 pathways, which may be responsible for the therapeutic efficacy of UC. The "component-metabolites-targets" interactive network indicated that Mag exerts its anti-UC effect by regulating PTGS1 and PTGS2, thereby regulating arachidonic acid. Moreover, the results of qRT-PCR showed that Mag could substantially decrease the relative mRNA expression level of Hub genes. In addition, it was found that Mag could inhibit the relative mRNA and protein expression of JAK2/STAT3 signaling pathway. The present results highlighted the role of Mag ameliorated colon injury in DSS-induced UC mice by inhibiting the JAK2/STAT3 signaling pathway. These results suggest that Mag may be an effective agent for the treatment of UC.PMID:39079890 | DOI:10.1002/ptr.8271

Free Radic Res. 2024 Jul 30:1-16. doi: 10.1080/10715762.2024.2386457. Online ahead of print.ABSTRACTOvarian cancer, marked by high rate of recurrence, novel therapeutic strategies are needed to improve patient outcome. One of the potential strategies is inducing ferroptosis in ovarian cancer cells. Ferroptosis is an iron-dependent, lipid peroxidation-driven mode of cell death primarily occurring on the cell membrane. PTRF, an integral component of the caveolae structures located on the cell membrane, is involved in a multitude of physiological processes, including but not limited to, endocytosis, signal transduction, and lipid metabolism. This study elucidates the relationship between PTRF and ferroptosis in ovarian cancer, offering a fresh perspective for the development of new therapeutic strategies. We knocked down PTRF employing siRNA in the ovarian cancer cell lines HEY and SKOV3, following which we stimulated ferroptosis with Erastin (Era). Our research indicates that the lack of PTRF sensitizes cancer cell to ferroptosis, likely by altering membrane stability and tension, thereby affecting signal pathways related to ferroptosis, such as lipid and atherosclerosis, fluid shear stress and atherosclerosis. Our findings provide new insights for developing new treatments for ovarian cancer.PMID:39079051 | DOI:10.1080/10715762.2024.2386457

J Proteome Res. 2024 Jul 30. doi: 10.1021/acs.jproteome.4c00138. Online ahead of print.ABSTRACTAcute respiratory distress syndrome (ARDS) is associated with high mortality rates, which are further exacerbated when accompanied by acute kidney injury (AKI). Presently, there is a lack of comprehensive studies thoroughly elucidating the metabolic dysregulation in ARDS patients with AKI leading to poor outcomes. We hypothesized that metabolomics can be a potent tool to highlight the differences in the metabolic profile unraveling unidentified pathophysiological mechanisms of ARDS patients with and without AKI. 1H nuclear magnetic resonance spectroscopy was used to identify key metabolites in the serum samples of 75 patients. Distinct clusters of both groups were obtained as the study's primary outcome using multivariate analysis. Notable alternations in the levels of nine metabolites were identified. Pathway analysis revealed the dysregulation of five significant cycles, which resulted in various complications, such as hyperammonemia, higher energy requirements, and mitochondrial dysfunction causing oxidative stress. Identified metabolites also showed a significant correlation with clinical scores, indicating severity. This study shows the alterations in the metabolite concentration highlighting the difference in the pathophysiology of both patient groups and its association with outcome, pointing in the direction of a personalized medicine approach and holding significant promise for application in critical care settings to improve clinical outcomes.PMID:39078945 | DOI:10.1021/acs.jproteome.4c00138

Anal Chem. 2024 Jul 30. doi: 10.1021/acs.analchem.3c04979. Online ahead of print.ABSTRACTMetabolomics commonly relies on using one-dimensional (1D) 1H NMR spectroscopy or liquid chromatography-mass spectrometry (LC-MS) to derive scientific insights from large collections of biological samples. NMR and MS approaches to metabolomics require, among other issues, a data processing pipeline. Quantitative assessment of the performance of these software platforms is challenged by a lack of standardized data sets with "known" outcomes. To resolve this issue, we created a novel simulated LC-MS data set with known peak locations and intensities, defined metabolite differences between groups (i.e., fold change > 2, coefficient of variation ≤ 25%), and different amounts of added Gaussian noise (0, 5, or 10%) and missing features (0, 10, or 20%). This data set was developed to improve benchmarking of existing LC-MS metabolomics software and to validate the updated version of our MVAPACK software, which added gas chromatography-MS and LC-MS functionality to its existing 1D and two-dimensional NMR data processing capabilities. We also included two experimental LC-MS data sets acquired from a standard mixture andMycobacterium smegmatiscell lysates since a simulated data set alone may not capture all the unique characteristics and variability of real spectra needed to assess software performance properly. Our simulated and experimental LC-MS data sets were processed with the MS-DIAL and XCMSOnline software packages and our MVAPACK toolkit to showcase the utility of our data sets to benchmark MVAPACK against community standards. Our results demonstrate the enhanced objectivity and clarity of software assessment that can be achieved when both simulated and experimental data are employed since distinctly different software performances were observed with the simulated and experimental LC-MS data sets. We also demonstrate that the performance of MVAPACK is equivalent to or exceeds existing LC-MS software programs while providing a single platform for processing and analyzing both NMR and MS data sets.PMID:39078713 | DOI:10.1021/acs.analchem.3c04979

J Robot Surg. 2024 Jul 30;18(1):301. doi: 10.1007/s11701-024-02037-y.ABSTRACTThis investigation sought to conduct a comprehensive meta-analysis to assess the comparative effectiveness and safety of percutaneous ablation (PCA) versus robotic-assisted partial nephrectomy (RAPN) among individuals diagnosed with cT1 renal tumors. This study rigorously followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review and meta-analysis. A systematic search was carried out in the PubMed, Embase, Web of Science, and Cochrane Library databases, focusing on studies published in English through February 2024. We focused on evaluating primary outcomes, specifically perioperative outcomes, functional outcomes, and oncological outcomes. In this analysis, data from 1534 patients across 13 studies were evaluated. PCA was found to have advantageous outcomes in comparison to RAPN regarding hospital stay durations, with a Weighted Mean Difference (WMD) of - 2.03 days (95% Confidence Interval [CI]: -3.78 to - 0.27; p = 0.02), operative times (WMD: -106.75 min; 95% CI: - 170.78 to - 42.72; p = 0.001), and overall complication rates (Odds Ratio [OR]: 0.61; 95% CI: 0.42 to 0.89; p = 0.01). Conversely, PCA showed a higher incidence of local recurrence compared to RAPN, with an OR of 3.20 (95% CI: 1.91 to 5.35; p < 0.00001). Moreover, there were no statistically significant differences between the two treatments in terms of major complications, declines in estimated glomerular filtration rates (eGFR), variations in creatinine levels, overall survival rates, and recurrence-free survival. While PCA exhibits higher local recurrence rates than RAPN, it also presents significant advantages, such as shorter hospital stays, decreased operative durations, and lower complication rates. This juxtaposition underscores the urgent need for further, more rigorous research to substantiate these findings.PMID:39078530 | DOI:10.1007/s11701-024-02037-y

Cell Mol Life Sci. 2024 Jul 30;81(1):320. doi: 10.1007/s00018-024-05361-6.ABSTRACTThe hypoxia response pathway enables adaptation to oxygen deprivation. It is mediated by hypoxia-inducible factors (HIF), which promote metabolic reprogramming, erythropoiesis, angiogenesis and tissue remodeling. This led to the successful development of HIF-inducing drugs for treating anemia and some of these molecules are now in clinic. However, elevated levels of HIFs are frequently associated with tumor growth, poor prognosis, and drug resistance in various cancers, including hepatocellular carcinoma (HCC). Consequently, there are concerns regarding the recommendation of HIF-inducing drugs in certain clinical situations. Here, we analyzed the effects of two HIF-inducing drugs, Molidustat and Roxadustat, in the well-characterized HCC cell line Huh7. These drugs increased HIF-1α and HIF-2α protein levels which both participate in inducing hypoxia response genes such as BNIP3, SERPINE1, LDHA or EPO. Combined transcriptomics, proteomics and metabolomics showed that Molidustat increased the expression of glycolytic enzymes, while the mitochondrial network was fragmented and cellular respiration decreased. This metabolic remodeling was associated with a reduced proliferation and a lower demand for pyrimidine supply, but an increased ability of cells to convert pyruvate to lactate. This was accompanied by a higher resistance to the inhibition of mitochondrial respiration by antimycin A, a phenotype confirmed in Roxadustat-treated Huh7 cells and Molidustat-treated hepatoblastoma cells (Huh6 and HepG2). Overall, this study shows that HIF-inducing drugs increase the metabolic resilience of liver cancer cells to metabolic stressors, arguing for careful monitoring of patients treated with HIF-inducing drugs, especially when they are at risk of liver cancer.PMID:39078527 | DOI:10.1007/s00018-024-05361-6

Cell Mol Life Sci. 2024 Jul 29;81(1):319. doi: 10.1007/s00018-024-05232-0.ABSTRACTStreptococcus pneumoniae (Spn) is the predominant pathogen responsible for community-acquired pneumonia (CAP) in children under five years old, and it can induce over 17% of pregnant women. However, no more effective measures exist to prevent infection induced by Spn in these two special populations. The beneficial microbes can antagonize Spn and provide new targets for preventing pneumococcal infections. This study used 16S rRNA gene sequencing and targeted metabolomics to evaluate the role of the Bacillus aerolatus CX253 (CX253) in alleviating Spn infection. Additionally, the colonization of CX253 was observed in nose, trachea, and lung by using confocal laser scanning microscopy and fluorescent labeling techniques. Compared with the model group, the expression level of interleukin-1β was dropped 1.81-fold and 2.22-fold, and interleukin-6 was decreased 2.39-fold and 1.84-fold. The express of tumor necrosis factor-α was down 2.30-fold and 3.84-fold in prevention group of childhood and pregnant rats, respectively. The 16S rRNA sequencing results showed that CX253 administration alone significantly increased the abundance of Lactobacillus, Limosilactobacillus, and Prevotella in the gut of childhood and pregnant rats. Furthermore, the CX253 increased propionate in the gut of childhood rats and increased propionate and butyrate in the gut of pregnant rats to inhibit pulmonary inflammation. In summary, CX253 attenuated Spn-induced inflammation by regulating the gut microbiota and SCFAs. The research provides valuable information for the prevention of pneumonia.PMID:39078497 | DOI:10.1007/s00018-024-05232-0

J Asian Nat Prod Res. 2024 Jul 30:1-24. doi: 10.1080/10286020.2024.2385365. Online ahead of print.ABSTRACTAn imbalanced microbiome is linked to several diseases, such as cancer, inflammatory bowel disease, obesity, and even neurological disorders. Bacteria and their by-products are used for various industrial and clinical purposes. The metabolites under discussion were chosen based on their biological impacts on host and gut microbiota interactions as established by metabolome research. The separation of bacterial metabolites by using statistics and machine learning analysis creates new opportunities for applications of bacteria and their metabolites in the environmental and medical sciences. Thus, the metabolite production strategies, methodologies, and importance of bacterial metabolites for human well-being are discussed in this review.PMID:39078342 | DOI:10.1080/10286020.2024.2385365

J Clin Endocrinol Metab. 2024 Jul 30:dgae515. doi: 10.1210/clinem/dgae515. Online ahead of print.NO ABSTRACTPMID:39078099 | DOI:10.1210/clinem/dgae515

Front Microbiol. 2024 Jul 15;15:1433892. doi: 10.3389/fmicb.2024.1433892. eCollection 2024.ABSTRACTOBJECTIVE: Osteoporosis, characterized by reduced bone density and heightened fracture risk, is influenced by genetic and environmental factors. This study investigates the interplay between gut microbiota, plasma metabolomics, and osteoporosis, identifying potential causal relationships mediated by plasma metabolites.METHODS: Utilizing aggregated genome-wide association studies (GWAS) data, a comprehensive two-sample Mendelian Randomization (MR) analysis was performed involving 196 gut microbiota taxa, 1,400 plasma metabolites, and osteoporosis indicators. Causal relationships between gut microbiota, plasma metabolites, and osteoporosis were explored.RESULTS: The MR analyses revealed ten gut microbiota taxa associated with osteoporosis, with five taxa positively linked to increased risk and five negatively associated. Additionally, 96 plasma metabolites exhibited potential causal relationships with osteoporosis, with 49 showing positive associations and 47 displaying negative associations. Mediation analyses identified six causal pathways connecting gut microbiota to osteoporosis through ten mediating relationships involving seven distinct plasma metabolites, two of which demonstrated suppression effects.CONCLUSION: This study provides suggestive evidence of genetic correlations and causal links between gut microbiota, plasma metabolites, and osteoporosis. The findings underscore the complex, multifactorial nature of osteoporosis and suggest the potential of gut microbiota and plasma metabolite profiles as biomarkers or therapeutic targets in the management of osteoporosis.PMID:39077745 | PMC:PMC11284117 | DOI:10.3389/fmicb.2024.1433892

Front Microbiol. 2024 Jul 15;15:1419686. doi: 10.3389/fmicb.2024.1419686. eCollection 2024.ABSTRACTINTRODUCTION: Revealing individual characteristics is supportive for identifying individuals in forensic crime. As saliva is one of the most common biological samples used in crime scenes, it is important to make full use of the rich individual information contained in saliva. The aim of this study was to explore the application of the microbiome in forensic science by analysing differences in the salivary microbiome and metabolome of healthy individuals with different dietary habits.METHODS: We performed 16S rDNA sequencing analysis based on oral saliva samples collected from 12 vegetarians, 12 seafood omnivores and 12 beef and lamb omnivores. Non-targeted metabolomics analyses were also performed based on saliva samples from healthy individuals.RESULTS: The results showed that the dominant flora of vegetarians was dominated by Neisseria (belonging to the phylum Proteobacteria), while seafood omnivores and beef and lamb omnivores were dominated by Streptococcus (belonging to the phylum Firmicutes). NDMS-based and cluster analyses showed that vegetarian dieters were significantly differentiated from meat dieters (seafood omnivores and beef and lamb omnivores), which may be related to the fact that high-fiber diets can create a different salivary flora structure. Variants were also detected in salivary metabolic pathways, including positive correlations with Lipid metabolism, Amino acid metabolism, Carbohydrate metabolism, and Nucleotide metabolism in vegetarians, and correlations in seafood omnivores. In order to select salivary microorganisms and metabolic markers that can distinguish different dietary profiles, a random forest classifier model was constructed in this study, and the results showed that individuals with different dietary profiles could be successfully distinguished based on the core genera and metabolites such as Streptococcus, Histidinyl-Valine.CONCLUSION: Our study provides a supportive basis for the application of salivary polyomics in order to reveal the dietary characteristics of individuals for forensic investigation and crime solving.PMID:39077734 | PMC:PMC11284149 | DOI:10.3389/fmicb.2024.1419686

Front Microbiol. 2024 Jul 15;15:1384463. doi: 10.3389/fmicb.2024.1384463. eCollection 2024.ABSTRACTBioelectrochemical systems offer unique opportunities to remove recalcitrant environmental pollutants in a net positive energy process, although it remains challenging because of the toxic character of such compounds. In this study, microbial fuel cell (MFC) technology was applied to investigate the benzene degradation process for more than 160 days, where glucose was used as a co-metabolite and a control. We have applied an inoculation strategy that led to the development of 10 individual microbial communities. The electrochemical dynamics of MFC efficiency was observed, along with their 1H NMR metabolic fingerprints and analysis of the microbial community. The highest power density of 120 mW/m2 was recorded in the final period of the experiment when benzene/glucose was used as fuel. This is the highest value reported in a benzene/co-substrate system. Metabolite analysis confirmed the full removal of benzene, while the dominance of fermentation products indicated the strong occurrence of non-electrogenic reactions. Based on 16S rRNA gene amplicon sequencing, bacterial community analysis revealed several petroleum-degrading microorganisms, electroactive species and biosurfactant producers. The dominant species were recognised as Citrobacter freundii and Arcobacter faecis. Strong, positive impact of the presence of benzene on the alpha diversity was recorded, underlining the high complexity of the bioelectrochemically supported degradation of petroleum compounds. This study reveals the importance of supporting the bioelectrochemical degradation process with auxiliary substrates and inoculation strategies that allow the communities to reach sufficient diversity to improve the power output and degradation efficiency in MFCs beyond the previously known limits. This study, for the first time, provides an outlook on the syntrophic activity of biosurfactant producers and petroleum degraders towards the efficient removal and conversion of recalcitrant hydrophobic compounds into electricity in MFCs.PMID:39077733 | PMC:PMC11284109 | DOI:10.3389/fmicb.2024.1384463

Rev Cardiovasc Med. 2023 Jun 8;24(6):169. doi: 10.31083/j.rcm2406169. eCollection 2023 Jun.ABSTRACTHigh-throughput metabolomics techniques are a useful tool to understand many disease conditions including cardiovascular disease such as valvular heart disease(s) (VHD). VHD involves damage to heart valves, mostly presenting as stenosis, regurgitation or prolapse and can be classified into degenerative, rheumatic, congenital, or prosthetic valve disease. Gaps remain in our understanding of the pathogenesis of the common VHD. It is now fitting to place into perspective the contribution of metabolomics in the mechanism of development, diagnosis, and prognosis of VHD. A structured search for metabolomics studies centred on human VHD was undertaken. Biomarkers associated with the pathogenesis of bicuspid aortic valve disease, mitral valve disease, rheumatic heart disease, and degenerative aortic valve stenosis are reviewed and discussed. In addition, metabolic biomarkers reported to prognosticate patient outcomes of post-valve repair or replacement are highlighted. Finally, we also review the pitfalls and limitations to consider when designing metabolomics studies, especially from a clinician's viewpoint. In the future, reliable and simple metabolic biomarker(s) may supplement the existing diagnostic tools in the early diagnosis of VHD.PMID:39077521 | PMC:PMC11264134 | DOI:10.31083/j.rcm2406169

Rev Cardiovasc Med. 2023 Mar 6;24(3):82. doi: 10.31083/j.rcm2403082. eCollection 2023 Mar.ABSTRACTCardiac aging is a natural process accompanied by cardiomyocyte hypertrophy and dysfunction. These changes can lead to adverse organ remodeling and ultimately lead to the development of heart failure. The study of cardiac aging is helpful to explore the mechanism of senescence and is of great significance for preventing cardiac aging. Cardiac aging is accompanied by changes in various metabolic functions. In this process, due to the change of metabolic substrates and enzyme activities, oxidative stress response increases, and reactive oxygen species (ROS) increases, accompanied by mitochondrial dysfunction and gene expression changes, so related protein metabolism also changes. Hormone metabolism and autophagy are also involved in the process of cardiac aging. Based on these findings, changes in diet, caloric restriction, improvement of mitochondrial function and promotion of autophagy have been proven to have positive effects in delaying cardiac aging. This article reviews the metabolic changes involved in the process of cardiac aging from different aspects, and briefly reviews the measures to improve cardiac aging.PMID:39077479 | PMC:PMC11264006 | DOI:10.31083/j.rcm2403082

Rev Cardiovasc Med. 2023 Jul 14;24(7):204. doi: 10.31083/j.rcm2407204. eCollection 2023 Jul.ABSTRACTAcute coronary syndrome (ACS) is a severe type of coronary heart disease (CHD) with increasing prevalence and significant challenges for prevention and treatment. Metabolomics is an emerging technology with intrinsic dynamics and flexibility to better delineate the phenotypic and metabolic alterations in organisms at the time of altered pathological states. It provides new insights into the complex pathological mechanisms of cardiovascular disease and contributes to the early detection, monitoring and evaluation of ACS. In this review, we analyze and summarize the literature related to ACS metabolomics which has contributed to the diagnosis and prevention of ACS.PMID:39077017 | PMC:PMC11266460 | DOI:10.31083/j.rcm2407204

PeerJ. 2024 Jul 26;12:e17757. doi: 10.7717/peerj.17757. eCollection 2024.ABSTRACTSoldiers of the Mexican Army with obesity were subjected to an intense 60-day weight-loss course consisting of a controlled diet, daily physical training, and psychological sessions. The nutritional treatment followed the European Society of Cardiology (ESC) recommendations, incorporating elements of the traditional milpa diet in the nutritional intervention. The total energy intake was reduced by 200 kcal every 20 days, starting with 1,800 kcal and ending with 1,400 kcal daily. On average, the participants reduced their body weight by 18 kg. We employed an innovative approach to monitor the progress of the twelve soldiers who completed the entire program. We compared the untargeted metabolomics profiles of their urine samples, taken before and after the course. The data obtained through liquid chromatography and high-resolution mass spectrometry (LC-MS) provided insightful results. Classification models perfectly separated the profiles pre and post-course, indicating a significant reprogramming of the participants' metabolism. The changes were observed in the C1-, vitamin, amino acid, and energy metabolism pathways, primarily affecting the liver, biliary system, and mitochondria. This study not only demonstrates the potential of rapid weight loss and metabolic pathway modification but also introduces a non-invasive method for monitoring the metabolic state of individuals through urine mass spectrometry data.PMID:39076775 | PMC:PMC11285361 | DOI:10.7717/peerj.17757

Front Endocrinol (Lausanne). 2024 Jul 15;15:1430720. doi: 10.3389/fendo.2024.1430720. eCollection 2024.ABSTRACTBACKGROUND: Bile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks.METHODS: In this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology.RESULTS: (1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets.CONCLUSION: This study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids.PMID:39076513 | PMC:PMC11284041 | DOI:10.3389/fendo.2024.1430720

Front Mol Biosci. 2024 Jul 15;11:1374316. doi: 10.3389/fmolb.2024.1374316. eCollection 2024.ABSTRACTIntroduction: Carnitine O-octanoyltransferase (CROT) is a well-established peroxisomal enzyme involved in liver fatty acid oxidation, but less is known about its recently discovered role in promoting vascular calcification, and whether CROT-dependent liver metabolism contributes to the latter. To date, CROT function in the context of calcification potential has been conducted in the dyslipidemic low-density lipoprotein receptor-deficient (Ldlr-/-) mice. Objectives: To differentiate peroxisome and CROT-dependent lipid biology from that of lipoprotein-mediated lipid biology, we therefore conducted a metabolomic analysis of the liver and plasma of normolipidemic CROT-deficient (Crot-/-) mice. Methods: We performed LC-MS-based metabolomics on liver and plasma derived from Crot-/- and Crot +/- mice and sibling Crot+/+ mice, using a dual-phase metabolite extraction protocol, and multiple LC-MS acquisition strategies. Results: We identified between 79 to 453 annotated metabolites from annotated metabolites from liver samples, and 117 to 424 annotated metabolites from plasma samples. Through differential abundance analysis, we determined that omega-3 fatty acids such as EPA, DPA, and DHA were higher in the liver of Crot-/- and Crot +/- mice than Crot+/+ mice. EPA were higher in plasma of Crot-/- mice than Crot+/+ mice. We also determined that the anti-inflammatory dicarboxylic acids, tetradecanedioic acid and azelaic acid, were higher in the plasma of CROT-deficient mice. Conclusion: Our study associated genetic CROT deletion with increased levels of anti-inflammatory molecules in mouse liver and plasma. These results suggest a potential mechanism for anti-calcification effects of CROT suppression and the potential use of omega-3 fatty acids as biomarkers for future CROT inhibition therapies.PMID:39076376 | PMC:PMC11284101 | DOI:10.3389/fmolb.2024.1374316

Beilstein J Org Chem. 2024 Jul 17;20:1635-1651. doi: 10.3762/bjoc.20.146. eCollection 2024.ABSTRACTMicrobulbifer is a genus of halophilic bacteria that are commonly detected in the commensal marine microbiomes. These bacteria have been recognized for their ability to degrade polysaccharides and other polymeric materials. Increasingly, Microbulbifer genomes indicate these bacteria to be an untapped reservoir for novel natural product discovery and biosynthetic novelty. In this review, we summarize the distribution of Microbulbifer bacteria, activities of the various polymer degrading enzymes that these bacteria produce, and an up-to-date summary of the natural products that have been isolated from Microbulbifer strains. We argue that these bacteria have been hiding in plain sight, and contemporary efforts into their genome and metabolome mining are going to lead to a proliferation of Microbulbifer-derived natural products in the future. We also describe, where possible, the ecological interactions of these bacteria in marine microbiomes.PMID:39076296 | PMC:PMC11285056 | DOI:10.3762/bjoc.20.146