PubMed

Ecotoxicol Environ Saf. 2024 Mar 28;275:116230. doi: 10.1016/j.ecoenv.2024.116230. Online ahead of print.ABSTRACTEpidemiological evidence on the health effects of pesticide exposure among greenhouse workers is limited, and the mechanisms are lacking. Building upon our team's previous population study, we selected two pesticides, CPF and EB, with high detection rates, based on the theoretical foundation that the liver serves as a detoxifying organ, we constructed a toxicity model using HepG2 cells to investigate the impact of individual or combined pesticide exposure on the hepatic metabolism profile, attempting to identify targeted biomarkers. Our results showed that CPF and EB could significantly affect the survival rate of HepG2 cells and disrupt their metabolic profile. There were 117 metabolites interfered by CPF exposure, which mainly affected ABC transporter, biosynthesis of amino acids, center carbon metabolism in cancer, fatty acid biosynthesis and other pathways, 95 metabolites interfered by EB exposure, which mainly affected center carbon metabolism in cancer, HIF-1 signaling pathway, valine, leucine and isoleucine biosynthesis, fatty acid biosynthesis and other pathways. The cross analysis and further biological experiments confirmed that CPF and EB pesticide exposure may affect the HIF-1 signaling pathway and valine, leucine and isoleucine biosynthesis in HepG2 cells, providing reliable experimental evidence for the prevention and treatment of liver damage in greenhouse workers.PMID:38552389 | DOI:10.1016/j.ecoenv.2024.116230

Ultrason Sonochem. 2024 Mar 25;105:106857. doi: 10.1016/j.ultsonch.2024.106857. Online ahead of print.ABSTRACTThis work investigated the effects of the combined use of thermosonication-preconditioned lactic acid bacteria (LAB) with the addition of ultrasound-assisted pineapple peel extracts (UU group) on the post-acidification potential, physicochemical and functional qualities of yogurt products, aimed at achieving prolonged preservation and enhancing functional attributes. Accordingly, the physical-chemical features, adhesion properties, and sensory profiles, acidification kinetics, the contents of major organic acids, and antioxidant activities of the differentially processed yogurts during refrigeration were characterized. Following a 14-day chilled storage process, UU group exhibited acidity levels of 0.5-2 oT lower than the control group and a higher lactose content of 0.07 mg/ml as well as unmodified adhesion potential, indicating that the proposed combination method efficiently inhibited post-acidification and delayed lactose metabolism without leading to significant impairment of the probiotic properties. The results of physicochemical analysis showed no significant changes in viscosity, hardness, and color of yogurt. Furthermore, the total phenolic content of UU-treated samples was 98 μg/mL, 1.78 times higher than that of the control, corresponding with the significantly lower IC50 values of DPPH and ABTS radical scavenging activities of the UU group than those of the control group. Observations by fluorescence inverted microscopy demonstrated the obvious adhesion phenomenon with no significant difference found among differentially prepared yogurts. The results of targeted metabolomics indicated the proposed combination strategy significantly modified the microbial metabolism, leading to the delayed utilization of lactose and the inhibited conversion into glucose during post-fermentation, as well as the decreased lactic acid production and a notable shift towards the formation of relatively weak acids such as succinic acid and citric acid. This study confirmed the feasibility of thermosonication-preconditioned LAB inocula, in combination with the use of natural active components from fruit processing byproducts, to alleviate post-acidification in yogurt and to enhance its antioxidant activities as well as simultaneously maintaining sensory features.PMID:38552299 | DOI:10.1016/j.ultsonch.2024.106857

Int Immunopharmacol. 2024 Mar 28;132:111946. doi: 10.1016/j.intimp.2024.111946. Online ahead of print.ABSTRACTEnsuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model. The study demonstrates that SPD administration (5 mg/kg/day) significantly corrects right ventricular impairment and pathological changes in pulmonary tissues following MCT exposure (60 mg/kg). Metabolomic profiling identified a purine metabolism disorder in MCT-treated rats, which SPD effectively normalized, conferring a protective effect against PAH progression. Subsequent in vitro analysis showed that SPD (0.8 mM) reduces oxidative stress and apoptosis in PAECs challenged with Dehydromonocrotaline (MCTP, 50 μM), likely by downregulating purine nucleoside phosphorylase (PNP) and modulating polyamine biosynthesis through alterations in S-adenosylmethionine decarboxylase (AMD1) expression and the subsequent production of decarboxylated S-adenosylmethionine (dcSAM). These findings advocate SPD's dual inhibitory effect on PNP and AMD1 as a novel strategy to conserve cellular ATP and alleviate oxidative injuries, thus providing a foundation for SPD's potential therapeutic application in PAH treatment.PMID:38552292 | DOI:10.1016/j.intimp.2024.111946

Comput Biol Med. 2024 Mar 26;173:108327. doi: 10.1016/j.compbiomed.2024.108327. Online ahead of print.ABSTRACTEndometrial cancer (EC) is one of the most common malignant tumors in women, and the increasing incidence and mortality pose a serious threat to the public health. Early diagnosis of EC could prolong the survival period and optimize the survivorship, greatly alleviating patients' suffering and social medical pressure. In this study, we collected urine and serum samples from the recruited patients, analyzed the samples using LC-MS approach, and identified the differential metabolites through metabolomic analysis. Then, the differentially expressed genes were identified through the systematic transcriptomic analysis of EC-related dataset from Gene Expression Omnibus (GEO), followed by network profiling of metabolic-reaction-enzyme-gene. In this experiment, a total of 83 differential metabolites and 19 hub genes were discovered, of which 10 different metabolites and 3 hub genes were further evaluated as more potential biomarkers based on network analysis. According to the KEGG enrichment analysis, the potential biomarkers and gene-encoded proteins were found to be involved in the arginine and proline metabolism, histidine metabolism, and pyrimidine metabolism, which was of significance for the early diagnosis of EC. In particular, the combination of metabolites (histamine, 1-methylhistamine, and methylimidazole acetaldehyde) as well as the combination of RRM2, TYMS and TK1 exerted more accurate discrimination abilities between EC and healthy groups, providing more criteria for the early diagnosis of EC.PMID:38552279 | DOI:10.1016/j.compbiomed.2024.108327

Mol Biol Evol. 2024 Mar 1;41(3):msae058. doi: 10.1093/molbev/msae058.ABSTRACTDomestication and artificial selection during production-oriented breeding have greatly shaped the level of genomic variability in sheep. However, the genetic variation associated with increased reproduction remains elusive. Here, two groups of samples from consecutively monotocous and polytocous sheep were collected for genome-wide association, transcriptomic, proteomic, and metabolomic analyses to explore the genetic variation in fecundity in Tibetan sheep. Genome-wide association study revealed strong associations between BMPR1B (p.Q249R) and litter size, as well as between PAPPA and lambing interval; these findings were validated in 1,130 individuals. Furthermore, we constructed the first single-cell atlas of Tibetan sheep ovary tissues and identified a specific mural granulosa cell subtype with PAPPA-specific expression and differential expression of BMPR1B between the two groups. Bulk RNA-seq indicated that BMPR1B and PAPPA expressions were similar between the two groups of sheep. 3D protein structure prediction and coimmunoprecipitation analysis indicated that mutation and mutually exclusive exons of BMPR1B are the main mechanisms for prolific Tibetan sheep. We propose that PAPPA is a key gene for stimulating ovarian follicular growth and development, and steroidogenesis. Our work reveals the genetic variation in reproductive performance in Tibetan sheep, providing insights and valuable genetic resources for the discovery of genes and regulatory mechanisms that improve reproductive success.PMID:38552245 | DOI:10.1093/molbev/msae058

ISME J. 2024 Mar 29:wrae055. doi: 10.1093/ismejo/wrae055. Online ahead of print.ABSTRACTViruses impact microbial systems through killing hosts, horizontal gene transfer, and altering cellular metabolism, consequently impacting nutrient cycles. A virus-infected cell, a "virocell", is distinct from its uninfected sister cell as the virus commandeers cellular machinery to produce viruses rather than replicate cells. Problematically, virocell responses to the nutrient-limited conditions that abound in nature are poorly understood. Here we used a systems biology approach to investigate virocell metabolic reprogramming under nutrient limitation. Using transcriptomics, proteomics, lipidomics, and endo- and exo-metabolomics, we assessed how low phosphate (low-P) conditions impacted virocells of a marine Pseudoalteromonas host when independently infected by two unrelated phages (HP1 and HS2). With the combined stresses of infection and nutrient limitation, a set of nested responses were observed. First, low-P imposed common cellular responses on all cells (virocells and uninfected cells), including activating the canonical P-stress response, and decreasing transcription, translation, and extracellular organic matter consumption. Second, low-P imposed infection-specific responses (for both virocells), including enhancing nitrogen assimilation and fatty acid degradation, and decreasing extracellular lipid relative abundance. Third, low-P suggested virocell-specific strategies. Specifically, HS2-virocells regulated gene expression by increasing transcription and ribosomal protein production, whereas HP1-virocells accumulated host proteins, decreased extracellular peptide relative abundance, and invested in broader energy and resource acquisition. These results suggest that although environmental conditions shape metabolism in common ways regardless of infection, virocell-specific strategies exist to support viral replication during nutrient limitation, and a framework now exists for identifying metabolic strategies of nutrient-limited virocells in nature.PMID:38552150 | DOI:10.1093/ismejo/wrae055

Discov Oncol. 2024 Mar 29;15(1):90. doi: 10.1007/s12672-024-00948-8.ABSTRACTBACKGROUND: Cervical cancer (CC) is a danger to women's health, especially in many developing countries. Metabolomics can make the connection between genotypes and phenotypes. It provides a wide spectrum profile of biological processes under pathological or physiological conditions.METHOD: In this study, we conducted plasma metabolomics of healthy volunteers and CC patients and integratively analyzed them with public CC tissue transcriptomics from Gene Expression Omnibus (GEO).RESULT: Here, we screened out a panel of 5 metabolites to precisely distinguish CC patients from healthy volunteers. Furthermore, we utilized multi-omics approaches to explore patients with stage I-IIA1 and IIA2-IV4 CC and comprehensively analyzed the dysregulation of genes and metabolites in CC progression. We identified that plasma levels of trimethylamine N-oxide (TMAO) were associated with tumor size and regarded as a risk factor for CC. Moreover, we demonstrated that TMAO could promote HeLa cell proliferation in vitro. In this study, we delineated metabolic profiling in healthy volunteers and CC patients and revealed that TMAO was a potential biomarker to discriminate between I-IIA1 and IIA2-IV patients to indicate CC deterioration.CONCLUSION: Our study identified a diagnostic model consisting of five metabolites in plasma that can effectively distinguish CC from healthy volunteers. Furthermore, we proposed that TMAO was associated with CC progression and might serve as a potential non-invasive biomarker to predict CC substage.IMPACT: These findings provided evidence of the important role of metabolic molecules in the progression of cervical cancer disease, as well as their ability as potential biomarkers.PMID:38551775 | DOI:10.1007/s12672-024-00948-8

Biomed Chromatogr. 2024 Mar 29:e5864. doi: 10.1002/bmc.5864. Online ahead of print.ABSTRACTAs one of the most common antipsychotics, olanzapine may cause metabolic-related adverse effects, but it is still unknown how olanzapine alters lipid metabolism. In this study, we found that olanzapine-treated mice showed varying degrees of dyslipidemia, which was particularly pronounced in female mice. Based on ultra-performance liquid chromatography-quadrupole time-of-flight-MS (UPLC-Q-TOF-MS) technology and lipid metabolomics, we mapped the changes in lipid metabolism in olanzapine-treated mice and then compared the changes in lipid metabolism between male and female mice. There were 98 metabolic differentiators between the olanzapine-treated and control groups in females and 79 in males. These metabolites were glycerolipids, glycerophospholipids, fatty amides, and sphingolipids, which are involved in glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. These results suggest that olanzapine-induced changes in the levels of lipid metabolites are closely associated with disturbances in lipid metabolic pathways, which may underlie lipemia. This lipidome profiling study not only visualizes changes in lipid metabolism in liver tissue but also provides a foundation for understanding the regulatory pathways and mechanisms involved in olanzapine-induced lipid metabolism disorders. Furthermore, this study demonstrates differences in lipid metabolism between males and females, providing a reference for clinical treatment regimen selection.PMID:38551083 | DOI:10.1002/bmc.5864

Comput Struct Biotechnol J. 2024 Feb 15;23:1226-1233. doi: 10.1016/j.csbj.2024.02.012. eCollection 2024 Dec.ABSTRACTIntegration of machine learning and high throughput measurements are essential to drive the next generation of the design-build-test-learn (DBTL) cycle in synthetic biology. Here, we report the use of active learning in combination with metabolomics for optimising production of surfactin, a complex lipopeptide resulting from a non-ribosomal assembly pathway. We designed a media optimisation algorithm that iteratively learns the yield landscape and steers the media composition toward maximal production. The algorithm led to a 160 % yield increase after three DBTL runs as compared to an M9 baseline. Metabolomics data helped to elucidate the underpinning biochemistry for yield improvement and revealed Pareto-like trade-offs in production of other lipopeptides from related pathways. We found positive associations between organic acids and surfactin, suggesting a key role of central carbon metabolism, as well as system-wide anisotropies in how metabolism reacts to shifts in carbon and nitrogen levels. Our framework offers a novel data-driven approach to improve yield of biological products with complex synthesis pathways that are not amenable to traditional yield optimisation strategies.PMID:38550972 | PMC:PMC10973723 | DOI:10.1016/j.csbj.2024.02.012

Camb Prism Precis Med. 2023 Feb 3;1:e17. doi: 10.1017/pcm.2023.4. eCollection 2023.ABSTRACTMedical practice is transforming from a reactive to a pro-active and preventive discipline that is underpinned by precision medicine. The advances in technologies in such fields as genomics, proteomics, metabolomics, transcriptomics and artificial intelligence have resulted in a paradigm shift in our understanding of specific diseases in childhood, greatly enhanced by our ability to combine data from changes within cells to the impact of environmental and population changes. Diseases in children have been reclassified as we understand more about their genomic origin and their evolution. Genomic discoveries, additional 'omics' data and advances such as optical genome mapping have driven rapid improvements in the precision and speed of diagnoses of diseases in children and are now being incorporated into newborn screening, have improved targeted therapies in childhood and have supported the development of predictive biomarkers to assess therapeutic impact and determine prognosis in congenital and acquired diseases of childhood. New medical device technologies are facilitating data capture at a population level to support higher diagnostic accuracy and tailored therapies in children according to predicted population outcome, and digital ecosystems now tailor therapies and provide support for their specific needs. By capturing biological and environmental data as early as possible in childhood, we can understand factors that predict disease or maintain health and track changes across a more extensive longitudinal path. Data from multiple health and external sources over long-time periods starting from birth or even in the in utero environment will provide further clarity about how to sustain health and prevent or predict disease. In this respect, we will not only use data to diagnose disease, but precision diagnostics will aid the 'diagnosis of good health'. The principle of 'start early and change more' will thus underpin the value of applying a personalised medicine approach early in life.PMID:38550930 | PMC:PMC10953773 | DOI:10.1017/pcm.2023.4

Camb Prism Precis Med. 2023 Feb 27;1:e15. doi: 10.1017/pcm.2023.3. eCollection 2023.ABSTRACTPrecision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.PMID:38550923 | PMC:PMC10953755 | DOI:10.1017/pcm.2023.3

Front Microbiol. 2024 Mar 14;15:1374646. doi: 10.3389/fmicb.2024.1374646. eCollection 2024.ABSTRACTPseudorabies virus can cause inflammation in the central nervous system and neurological symptoms. To further investigate the protective mechanism of PRV XJ delgE/gI/TK in the central nervous system, an intracranial PRV-infection mice model was developed. The results demonstrated that immunization with PRV XJ delgE/gI/TK successfully prevented death caused by PRV-intracranial infection. Subsequently, the brains were collected for transcriptome and metabolome analysis. GO and KEGG enrichment analysis indicated that the differentially expressed genes were primarily enriched in pathways such as TNF, NOD-like receptor, JAK-STAT, MAPK, IL-17 and apoptosis signaling. Metabolomics analysis revealed that the differential metabolites were mainly associated with pathways such as fatty acid degradation, arachidonic acid metabolism, linoleic acid metabolism and unsaturated fatty acid biosynthesis. The combined analysis of metabolites and differentially expressed genes revealed a strong correlation between the differential metabolites and TNF, PI3K, and MAPK signaling pathways. Anti-inflammatory metabolites have been shown to inhibit the inflammatory response and prevent mouse death caused by PRV infection. Notably, when glutathione was injected intracranially and dihydroartemisinin was injected intraperitoneally, complete protection against PRV-induced death in mice was observed. Moreover, PRV activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrates that PRV XJ delgE/gI/TK can protects intracranially infected mice from death by regulating various metabolites with anti-inflammatory functions post-immunization.PMID:38550870 | PMC:PMC10972889 | DOI:10.3389/fmicb.2024.1374646

Front Cell Infect Microbiol. 2024 Mar 14;14:1340610. doi: 10.3389/fcimb.2024.1340610. eCollection 2024.ABSTRACTBACKGROUND: Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed to determine whether the plasma metabolomic profile of PWH on long-term suppressive ART and immunologically recovered approximates the normality by comparison with healthy controls with similar age and gender.METHODS: We carried out a cross-sectional study in 17 PWH on long-term ART (HIV-RNA <50 copies/mL, CD4+ ≥500 cells/mm3, and CD4+/CD8+ ≥1) and 19 healthy controls with similar age and gender. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and Generalized Linear Models (GLM) with a gamma distribution (log-link). Significance levels (p-value) were corrected for multiple testing (q-value).RESULTS: PCA and PLS-DA analyses found no relevant differences between groups. Adjusted GLM showed 14 significant features (q-value<0.20), of which only three could be identified: lysophosphatidylcholine (LysoPC) (22:6) (q-value=0.148), lysophosphatidylethanolamine (LysoPE) (22:6) (q-value=0.050) and hydroperoxy-octadecatrienoic acid (HpOTrE)/dihydroperoxy-octadecatrienoic acid (DiHOTrE)/epoxy-octadecadienoic acid (EpODE) (q-value=0.136). These significant identified metabolites were directly correlated to plasma inflammatory biomarkers in PWH and negatively correlated in healthy controls.CONCLUSION: PWH on long-term ART have a metabolomic profile that is almost normal compared to healthy controls. Nevertheless, residual metabolic alterations linked to inflammatory biomarkers persist, which could favor the development of age-related comorbidities among this population.PMID:38550617 | PMC:PMC10972849 | DOI:10.3389/fcimb.2024.1340610

Front Plant Sci. 2024 Mar 14;15:1326998. doi: 10.3389/fpls.2024.1326998. eCollection 2024.ABSTRACTINTRODUCTION: Dendrobium is an epiphytic herb plant with neuroprotective, gastroprotective, anti-inflammatory, and immunomodulatory effects. It is often found attached to tree trunks or rocks. With the development of the dendrobium industry, numerous epiphytic patterns exist, such as crushed stone, stump, and sawdust. The study of metabolites and endophytes of D. nobile under different epiphytic patterns, which revealed the effects of epiphytic patterns on D. nobile from the perspectives of metabolomics and microbiology, is of great significance for the healthy development of D. nobile.METHODS: In the study, the D. nobile under five epiphytic patterns grown in the same environment were selected. The metabolites were investigated by widely targeted metabolomics, and the endophytes were sequenced using high-throughput sequencing methods. Then, a correlation analysis between the different metabolites and endophytes was performed.RESULTS: A total of 1,032 metabolites were annotated in D. nobile. There are more flavonoids and phenolic acids accumulated on the epiphytic pattern of Danxia stone, whereas the accumulation of lipids on the other epiphytic patterns and 16 differential metabolites was screened out. The endophyte composition of D. nobile was dominated by Proteobacteria, Actinomycetes, unidentified bacteria, Firmicutes, and Cyanobacteria. For endophytic fungi, Basidiomycota and Ascomycota were the dominant phyla of D. nobile. The relative abundance of Spirosoma, Nocardioides, and Arrhenia in the Danxia stone was significantly higher than that of other epiphytic patterns. According to correlation analysis, we found a significant correlation between differential metabolites and Spirosoma, Nocardioides, and Arrheni.DISCUSSION: This study confirmed that Dendrobium quality was affected by its epiphytic patterns and revealed its possible causes from a microbiological point of view.PMID:38550286 | PMC:PMC10972854 | DOI:10.3389/fpls.2024.1326998

Oncol Lett. 2024 Mar 14;27(5):209. doi: 10.3892/ol.2024.14342. eCollection 2024 May.ABSTRACTBreast cancer (BC) is the most common type of malignancy and the leading cause of cancer-associated mortality in women worldwide. As such, assessing the metabolic changes during human breast carcinogenesis is key for developing disease prevention methods and treatment. In the present study, non-targeted metabolomics with chemometrics based on ultra-high performance liquid chromatography-high-resolution mass spectrometry were performed to assess differences in serum metabolite patterns between patients with BC and healthy individuals. A total of 3,246 metabolites in the sera of healthy controls and patients with BC were found. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that arginine, proline, nicotinate, nicotinamide, caffeine and arachidonic acid metabolism, as well as fatty acid biosynthesis were significantly altered in patients with BC in comparison with controls. These results suggested that serum metabolic profiling has potential for discovering molecular biomarkers for the detection of BC. It may also further the understanding of the underlying mechanisms associated with this disease.PMID:38549802 | PMC:PMC10973928 | DOI:10.3892/ol.2024.14342

Natl Sci Rev. 2024 Jan 29;11(3):nwae039. doi: 10.1093/nsr/nwae039. eCollection 2024 Mar.ABSTRACTMitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer (CRC) cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione (GSH) via the upregulation of RRM2B-a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3'UTR of RRM2B increased its mRNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence (CDS) of OPA1-an essential GTPase protein for mitochondrial inner membrane fusion-also increased mRNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development.PMID:38549713 | PMC:PMC10977914 | DOI:10.1093/nsr/nwae039

Cardiovasc Hematol Agents Med Chem. 2024 Feb 15. doi: 10.2174/0118715257282030240130095754. Online ahead of print.ABSTRACTOverproduction of reactive nitrogen and oxygen species (RNS and ROS) has been linked to the pathogenesis of diabetes, hypertension, hyperlipidemia, stroke, angina, and other cardiovascular diseases. These species are produced in part by the mitochondrial respiratory chain, NADPH oxidase, and xanthine oxidase. RNS and ROS both contribute to oxidative stress, which is necessary for the development of cardiovascular disorders. In addition to ROS species like hydroxyl ion, hydrogen peroxide, and superoxide anion, RNS species like nitric oxide, peroxynitrous acid, peroxynitrite, and nitrogen dioxide radicals have also been linked to a number of cardiovascular conditions. They promote endothelial dysfunction, vascular inflammation, lipid peroxidation, and oxidative damage, all of which contribute to the development of cardiovascular pathologies. It's crucial to understand the mechanisms that result in the production of RNS and ROS in order to identify potential therapeutic targets. Redox biomarkers serve as indicators of oxidative stress, making them crucial tools for diagnosing and predicting cardiovascular states. The advancements in proteomics, metabolomics, genomics, and transcriptomics have made the identification and detection of these small molecules possible. The following redox biomarkers are notable examples: 3-nitrotyrosine, 4-hydroxy-2-nonenal, 8- iso-prostaglandin F2, 8-hydroxy-2-deoxyguanosine, malondialdehyde, Diacron reactive oxygen metabolites, total thiol, and specific microRNAs (e.g. miRNA199, miRNA21, miRNA1254, miRNA1306-5p, miRNA26b-5p, and miRNA660-5p) are examples. Although redox biomarkers have great potential, their clinical applicability faces challenges. Redox biomarkers frequently have a short half-life and exist in small quantities in the blood, making them challenging to identify and measure. The interpretation of biomarker data may also be influenced by confounding factors and the complex interplay of various oxidative stress pathways. Therefore, in-depth validation studies and the development of sensitive and precise detection methods are needed to address these problems. In the search for redox biomarkers, cutting-edge techniques like mass spectrometry, immunoassays, and molecular diagnostics are applied. New platforms and technologies have made it possible to accurately detect and monitor redox biomarkers, which facilitates their use in clinical settings. Our expanding knowledge of RNS and ROS involvement in cardiovascular disorders has made it possible to develop redox biomarkers as diagnostic and prognostic tools. Overcoming the challenges associated with their utility and utilizing advanced detection techniques, which will improve their clinical applicability, will ultimately benefit the management and treatment of cardiovascular conditions.PMID:38549520 | DOI:10.2174/0118715257282030240130095754

Mol Nutr Food Res. 2024 Mar 29:e2300797. doi: 10.1002/mnfr.202300797. Online ahead of print.ABSTRACTSCOPE: l-Theanine (l-Thea) is an amino acid which is naturally present in tea leaves. It has been associated with possible health advantages, including obesity prevention, but the underlying molecular mechanisms have not been elucidated.METHODS AND RESULTS: A multiomics approach is utilized to examine the mechanism by which l-Thea exerts its antiobesity effects. This study reveals that l-Thea administration significantly ameliorates high-fat diet (HFD)-induced obesity in rats by improving body weight and hyperlipidemia. l-Thea mitigates HFD-induced inflammation and reverses hepatic and colonic damage, and intestinal barrier. This research verifies that the preventive effect of l-Thea on obesity in rats induced by an HFD with colitis is accomplished by suppressing the phosphorylation of important proteins in the NF-κB/mitogen-activated protein kinase (MAPK) pathways. Metabolome analysis reveals that l-Thea regulates HFD-induced metabolic disorders, specifically through modulation of steroid hormone biosynthesis. Microbiome analysis reveals that l-Thea mitigates HFD-induced dysbiosis by increasing the relative abundance of obesity-associated probiotic bacteria, including Blautia coccoides and Lactobacillus murinus, while simultaneously suppressing the abundance of pathogenic bacteria.CONCLUSIONS: l-Thea alleviates colitis generated by an HFD by restoring the integrity of the intestinal barrier, suppressing inflammation through regulation of MAPK/NF-κB signaling pathways, and enhancing microbial metabolism in colon.PMID:38549456 | DOI:10.1002/mnfr.202300797

One Health Outlook. 2024 Mar 29;6(1):4. doi: 10.1186/s42522-024-00100-0.ABSTRACTBACKGROUND: Different production systems of livestock animals influence various factors, including the gut microbiota.METHODS: We investigated whether changing the conditions from barns to free-range chicken farming impacts the microbiome over the course of three weeks. We compared the stool microbiota of chicken from industrial barns after introducing them either in community or separately to a free-range environment.RESULTS: Over the six time points, 12 taxa-mostly lactobacilli-changed significantly. As expected, the former barn chicken cohort carries more resistances to common antibiotics. These, however, remained positive over the observed period. At the end of the study, we collected eggs and compared metabolomic profiles of the egg white and yolk to profiles of eggs from commercial suppliers. Here, we observed significant differences between commercial and fresh collected eggs as well as differences between the former barn chicken and free-range chicken.CONCLUSION: Our data indicate that the gut microbiota can undergo alterations over time in response to changes in production systems. These changes subsequently exert an influence on the metabolites found in the eggs. The preliminary results of our proof-of-concept study motivate larger scale observations with more individual chicken and longer observation periods.PMID:38549118 | DOI:10.1186/s42522-024-00100-0

Methods Mol Biol. 2024;2758:241-254. doi: 10.1007/978-1-0716-3646-6_13.ABSTRACTHen eggs and the corresponding food products are essential components of human diet. In addition to supplying basic nutrients, they contain functional peptides that are released in vivo within the intact raw material following physiological proteolytic events affecting specific proteins or derive from technological processing of albumen and yolk fractions as a result of the dedicated use of proteases from plant and microbial sources. Besides their potential importance for functional applications, peptides released under physiological conditions in intact egg can be used as markers of product storage and deterioration. Therefore, characterization and quantitation of peptides in egg and egg-derived products can be used to implement evaluation of potential bioactivities as well as to assess food product qualitative characteristics. Here, we provide dedicated information on extraction, identification, and quantitative analysis of peptides from albumen and yolk plasma; nano-liquid chromatography-mass spectrometry combined with bioinformatic analysis of resulting raw data by different software tools allowed to assign molecules based on database searching and to evaluate their relative quantity in different samples.PMID:38549018 | DOI:10.1007/978-1-0716-3646-6_13