PubMed

Environ Sci Technol. 2024 Aug 22. doi: 10.1021/acs.est.4c01341. Online ahead of print.ABSTRACTMedium-chain chlorinated paraffins (MCCPs, C14-C17) are frequently detected in diverse environmental media. It has been proposed to be listed in Annex A of the Convention on Persistent Organic Pollutants in 2023. Although MCCPs are a crucial health concern, their toxicity remains unclear. This study investigated the toxic effects of MCCPs (0.1-50 mg/kg body weight/day) on the thyroid gland of female Sprague-Dawley rats and characterized the potential toxic pathways via transcriptomics and metabolomics approaches. MCCPs exposure caused histopathological changes to the endoplasmic reticula and mitochondria in thyroid follicular cells at a dose of 50 mg/kg bw/d and increased serum thyrotropin-releasing hormone, thyroid-stimulating hormones, and thyroxine when exposed to a higher dose of MCCPs. Transcriptomic analysis indicated the excessive expression of key genes related to thyroid hormone synthesis induced by MCCPs. Integrating the dual-omics analysis revealed mitochondrial dysfunction of the thyroid by mediating fatty acid oxidation, Kreb's cycle, and oxidative phosphorylation. Significant metabolic toxicity on the thyroid might be linked to the characteristics of the chlorine content of MCCPs. This study revealed the toxicity of MCCPs to the thyroid gland via triggering thyroid hormone synthesis and interfering with mitochondrial function, which can provide new insights into the modes of action and mechanism-based risk assessment of MCCPs.PMID:39172767 | DOI:10.1021/acs.est.4c01341

PLoS Pathog. 2024 Aug 22;20(8):e1012435. doi: 10.1371/journal.ppat.1012435. eCollection 2024 Aug.ABSTRACTEntamoeba histolytica is a protozoan parasite belonging to the phylum Amoebozoa that causes amebiasis, a global public health problem. E. histolytica alternates its form between a proliferative trophozoite and a dormant cyst. Trophozoite proliferation is closely associated with amebiasis symptoms and pathogenesis whereas cysts transmit the disease. Drugs are available for clinical use; however, they have issues of adverse effects and dual targeting of disease symptoms and transmission remains to be improved. Development of new drugs is therefore urgently needed. An untargeted lipidomics analysis recently revealed structural uniqueness of the Entamoeba lipidome at different stages of the parasite's life cycle involving very long (26-30 carbons) and/or medium (8-12 carbons) acyl chains linked to glycerophospholipids and sphingolipids. Here, we investigated the physiology of this unique acyl chain diversity in Entamoeba, a non-photosynthetic protist. We characterized E. histolytica fatty acid elongases (EhFAEs), which are typically components of the fatty acid elongation cycle of photosynthetic protists and plants. An approach combining genetics and lipidomics revealed that EhFAEs are involved in the production of medium and very long acyl chains in E. histolytica. This approach also showed that the K3 group herbicides, flufenacet, cafenstrole, and fenoxasulfone, inhibited the production of very long acyl chains, thereby impairing Entamoeba trophozoite proliferation and cyst formation. Importantly, none of these three compounds showed toxicity to a human cell line; therefore, EhFAEs are reasonable targets for developing new anti-amebiasis drugs and these compounds are promising leads for such drugs. Interestingly, in the Amoebazoan lineage, gain and loss of the genes encoding two different types of fatty acid elongase have occurred during evolution, which may be relevant to parasite adaptation. Acyl chain diversity in lipids is therefore a unique and indispensable feature for parasitic adaptation of Entamoeba.PMID:39172749 | DOI:10.1371/journal.ppat.1012435

J Infect Dis. 2024 Aug 22:jiae418. doi: 10.1093/infdis/jiae418. Online ahead of print.ABSTRACTBACKGROUND: Microbiota-based treatments are effective in preventing recurrent Clostridioides difficile infection (rCDI). Fecal microbiota, live-jslm (REBYOTA®; RBL, previously RBX2660) was shown to prevent rCDI in a phase 3, randomized, double-blinded placebo controlled clinical trial (PUNCH™ CD3).METHODS: Stool samples from participants in PUNCH™ CD3 who received a single blinded dose of rectally administered RBL or placebo were sequenced to determine microbial community composition and calculate the Microbiome Health Index for post-antibiotic dysbiosis (MHI-A). The composition of bile acids (BAs) in the same samples was quantified by liquid chromatography mass spectrometry. Relationships between BA composition and microbiota community structure and correlations with treatment outcomes were assessed.RESULTS: Before administration, Gammaproteobacteria and Bacilli dominated the microbiota community and primary BAs were more prevalent than secondary BAs. Clinical success after administration correlated with shifts to predominantly Bacteroidia and Clostridia, a significant increase in MHI-A, and a shift from primary to secondary BAs. Several microbiota and BA changes were more extensive in RBL-treated responders compared to placebo-treated responders, and microbiota changes correlated with BA changes.CONCLUSIONS: Clinical response and RBL administration were associated with significant restoration of microbiota and BA composition.CLINICAL TRIALS REGISTRATION: NCT03244644.PMID:39172632 | DOI:10.1093/infdis/jiae418

Cardiovasc Res. 2024 Aug 22:cvae177. doi: 10.1093/cvr/cvae177. Online ahead of print.ABSTRACTAs the global demographic landscape continues to shift towards an aged population, so does the medical and socioeconomic burden of cardiovascular diseases. Indeed, ageing is one of, if not the, key risk factor for the development of cardiovascular diseases. However, there are currently no approved cardiovascular therapeutics that primarily target the molecular and cellular mechanisms underlying the ageing process itself. In this review, we present the potential of emerging anti-ageing strategies, including epigenetic rejuvenation, metabolic reprogramming, autophagy activation, as well as senolytic and anti-inflammatory therapies, in delaying or reversing the development of age-related cardiovascular disorders, while considering potential sex differences. In doing so, we implicate cellular ageing processes in the pathogenesis of several prevalent cardiovascular diseases, such as atherosclerosis, hypertension, various types of cardiomyopathies (including its hypertrophic, ischemic, dilated, diabetic, and arrhythmogenic forms) and heart failure, particularly that with preserved ejection fraction. Finally, we outline future challenges and steps needed for the implementation of these novel anti-ageing strategies in the clinical setting, with the aim of challenging the long-held notion of ageing as a 'nonmodifiable' risk factor for cardiovascular diseases.PMID:39172536 | DOI:10.1093/cvr/cvae177

Pest Manag Sci. 2024 Aug 22. doi: 10.1002/ps.8367. Online ahead of print.ABSTRACTBACKGROUND: Stilbenoid extracts, such as those originating from grapevine by-products (e.g. canes), are of interest for use as biopesticides in vineyard owing to their antimicrobial activities. However, stilbenoids are unstable in the environment, especially under light. This study aimed to chemically characterize the effect of UV light on stilbenoids present in a grapevine cane extract (CE), and to evaluate the antimicrobial activities against two major grapevine pathogens (Plasmopara viticola and Botrytis cinerea) of grapevine extracts exposed to UV.RESULTS: Treatment with UV (365 nm) on a grapevine CE led to degradation of stilbenoids (up to 71% after 1 h). The stilbenoid stability depended on their chemical structure: only those possessing CC, as trans-resveratrol and trans-ε-viniferin, were affected with first their isomerization and secondly their oxidation/cyclization. As a consequence, UV-exposed extracts (UV-CEs) showed reduced antimicrobial activities against the two pathogens (mycelium and spores). For instance, regarding P. viticola, an UV-CE exposed during 4 h showed an almost total loss of its activity on oomycete development and a 2.4-fold inhibition of zoospore mobility in comparison to CE. For B. cinerea, the inhibition capacity of the same UV-CE was reduced by only 1.1-fold on mycelial development and by 3.2-fold on conidial germination compared to CE.CONCLUSION: UV light triggered modifications on the structure of bioactive stilbenoids, resulting in losses of their antimicrobial activities. Photoprotection of stilbenoids has to be considered in the perspective of using them in vineyards as biopesticides. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.PMID:39172057 | DOI:10.1002/ps.8367

FASEB J. 2024 Aug 31;38(16):e70005. doi: 10.1096/fj.202400553R.ABSTRACTEndothelial dysfunction, prevalent in cardiovascular diseases (CVDs) and linked to conditions like diabetes, hypertension, obesity, renal failure, or hypercholesterolemia, is characterized by diminished nitric oxide (NO) bioavailability-a key signaling molecule for vascular homeostasis. Current two-dimensional (2D) in vitro studies on NO synthesis by endothelial cells (ECs) lack the crucial laminar shear stress, a vital factor in modulating the NO-generating enzyme, endothelial nitric oxide synthase (eNOS), under physiological conditions. Here we developed a tracer-based metabolomics approach to measure NO-specific metabolites with mass spectrometry (MS) and show the impact of fluid flow on metabolic parameters associated with NO synthesis using 2D and 3D platforms. Specifically, we tracked the conversion of stable-isotope labeled NO substrate L-Arginine to L-Citrulline and L-Ornithine to determine eNOS activity. We demonstrated clear responses in human coronary artery endothelial cells (HCAECs) cultured with 13C6, 15N4-L-Arginine, and treated with eNOS stimulator, eNOS inhibitor, and arginase inhibitor. Analysis of downstream metabolites, 13C6, 15N3 L-Citrulline and 13C5, 15N2 L-Ornithine, revealed distinct outcomes. Additionally, we evaluated the NO metabolic status in static 2D culture and 3D microvessel models with bidirectional and unidirectional fluid flow. Our 3D model exhibited significant effects, particularly in microvessels exposed to the eNOS stimulator, as indicated by the 13C6, 15N3 L-Citrulline/13C5, 15N2 L-Ornithine ratio, compared to the 2D culture. The obtained results indicate that the 2D static culture mimics an endothelial dysfunction status, while the 3D model with a unidirectional fluid flow provides a more representative physiological environment that provides a better model to study endothelial dysfunction.PMID:39171967 | DOI:10.1096/fj.202400553R

J Integr Plant Biol. 2024 Aug 22. doi: 10.1111/jipb.13763. Online ahead of print.ABSTRACTDuring their co-evolution with herbivorous insects, plants have developed multiple defense strategies that resist pests, such as releasing a blend of herbivory-induced plant volatiles (HIPVs) that repel pests or recruit their natural enemies. However, the responses of insects to HIPVs in maize (Zea mays L.) are not well understood. Here, we demonstrate that the Asian corn borer (ACB, Ostrinia furnacalis), a major insect pest of maize, shows a preference for maize pre-infested with ACB larvae rather than being repelled by these plants. Through combined transcriptomic and metabolomics analysis of ACB-infested maize seedlings, we identified two substances that explain this behavior: (E)-4,8-dimethylnona-1,3,7-triene (DMNT) and (3E,7E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene (TMTT). DMNT and TMTT attracted ACB larvae, and knocking out the maize genes responsible for their biosynthesis via gene editing impaired this attraction. External supplementation with DMNT/TMTT hampered the larvae's ability to locate pre-infested maize. These findings uncover a novel role for DMNT and TMTT in driving the behavior of ACB. Genetic modification of maize to make it less detectable by ACB might be an effective strategy for developing maize germplasm resistant to ACB and for managing this pest effectively in the field.PMID:39171839 | DOI:10.1111/jipb.13763

Cancer Sci. 2024 Aug 22. doi: 10.1111/cas.16323. Online ahead of print.ABSTRACTApproximately 660,000 women are diagnosed with cervical cancer annually. Current screening options such as cytology or human papillomavirus testing have limitations, creating a need to identify more effective ancillary biomarkers for triage. Here, we evaluated whether metabolomic analysis of cervical mucus metabolism could be used to identify biomarkers of cervical intraepithelial neoplasia (CIN) and cervical cancer. The case-control group consisted of 181 CIN, 69 squamous cell carcinoma (SCC) patients, and 48 healthy controls in the primary cohort. We undertook metabolomic analyses using ultra-HPLC-tandem mass spectrometry. Univariate and multivariate analyses were carried out to profile metabolite characteristics, and receiver operating characteristic (ROC) analysis identified biomarker candidates. Five metabolites conferred the highest discriminatory power for SCC: oxidized glutathione (GSSG) (area under the ROC curve, 0.924; 95% confidence interval, 0.877-0.971), malic acid (0.914, 0.859-0.968), kynurenine (0.884, 0.823-0.945), GSSG/glutathione (GSH) (0.936, 0.892-0.979), and kynurenine/tryptophan (0.909, 0.856-0.961). Malic acid was the best marker for detection of CIN2 or worse (0.858, 0.793-0.922) and was a clinically useful metabolite. We confirmed the reproducibility of the results by validation cohort. Additionally, metabolomic analyses revealed eight pathways strongly associated with cervical neoplasia. Of these, only the tricarboxylic acid cycle was strongly associated with all CINs and cancer, indicating active energy production. Aberrant arginine metabolism by decreasing arginine and increasing citrulline might reduce tumor immunity. Changes in cysteine-methionine and GSH pathways might drive the initiation and progression of cervical cancer. These results suggest that metabolic analysis can identify ancillary biomarkers and could improve our understanding of the pathophysiological mechanisms underlying cervical neoplasia.PMID:39171738 | DOI:10.1111/cas.16323

Exp Dermatol. 2024 Aug;33(8):e15165. doi: 10.1111/exd.15165.ABSTRACTPhenylalanine is a crucial amino acid in the process of melanogenesis. However, the exact mechanism by which it is transported into melanocytes has not been disclosed. The aim of this study was to identify and examine the key transporters that are responsible for phenylalanine transportation and evaluate their significance in melanogenesis. The amino acid transporter SLC16A10 was found to be up-regulated in both melasma (GSE72140) and sun-exposed skin (GSE67098). The protein levels of SLC16A10 were proportional to the melanin content in melanocytic nevi, indicating that SLC16A10 was related to melanogenesis. After SLC16A10 overexpression, melanin increased significantly in MNT1 cells. Meanwhile, the expression of melanogenesis-related proteins such as TYR and TYRP1 increased, while their RNA levels did not change. Transcriptomics data indicated that SLC16A10 can enhance the function of ribosome. Furthermore, targeted metabolomics data and ELISA results demonstrated SLC16A10 mainly affected the transport of phenylalanine into the cells. Then, phenylalanine was added to the cell culture medium after SLC16A10 overexpression, melanin synthesis in cells furtherly increased, which verified that SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine. Finally, we found that SLC16A10 expression increased after UVB irradiation. Knockdown SLC16A10 reduced UVB-induced melanin production and phenylalanine uptake by cells. In summary, SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine, and upregulation SLC16A10 is likely responsible for the UVB-induced hyperpigmentation as well.PMID:39171634 | DOI:10.1111/exd.15165

Food Funct. 2024 Aug 22. doi: 10.1039/d4fo02233e. Online ahead of print.ABSTRACTThe main constituents of saffron are the apocarotenoids crocins and crocetin, present in the stigmas. Numerous healthy properties, especially those related to the effects on the central nervous system, have been attributed to these compounds but the metabolites responsible for these effects are still unknown. Previous evidences in animal models suggest a role for the gut microbiota in the pharmacokinetics and the neuroprotective effects of these compounds. However, the interaction between these apocarotenoids and the gut microbiota has been poorly studied. In this article, we have thoroughly investigated the batch fermentation of crocin-1 and crocetin (10 μM) with human fecal samples of two donors at different incubation times (0-240 h) using a metabolomic approach. We corroborated a rapid transformation of crocin-1 which looses the glucose molecules through de-glycosylation reactions until its complete transformation into crocetin in 6 hours. A group of intermediate crocins with different degrees of glycosylation were detected in a very short time. Crocetin was further metabolized and new microbial metabolites produced by double-bond reduction and demethylation reactions were identified for the first time: dihydro and tetrahydro crocetins and di-demethyl crocetin. In addition, we detected changes in the levels of the short chain fatty acids valeric acid and hexanoic acid suggesting further structural modifications of crocetin or changes in the catabolic production of these compounds. This research is a pioneering study of the action of the human gut microbiota on the saffron apocarotenoids and goes one step further towards the discovery of metabolites potentially involved in the benefits of saffron.PMID:39171480 | DOI:10.1039/d4fo02233e

J Sci Food Agric. 2024 Aug 22. doi: 10.1002/jsfa.13832. Online ahead of print.ABSTRACTBACKGROUND: Genetic breeding is essential to develop grapevine genotypes adapted to warm climates and resistant to pathogens. Traditionally cultivated Vitis vinifera is susceptible to biotic and abiotic stresses. Winemakers and consumers, however, perceive wines from non-vinifera or hybrid cultivars as inferior. In this study, sensory analyses and comprehensive metabolite profiling by targeted and untargeted approaches were used to investigate the oenological potential of wines from grapes of genotypes developed throughout four breeding cycles to improve climate adaptation, sugar contents and berry color.RESULTS: Novel genotypes had higher yields and the wines exhibited increased contents of polyphenols, including anthocyanins. Volatile monoterpenes in the wines decreased throughout breeding cycles in the absence of selective pressure. Polyphenol contents were higher in intermediate wines, with hydroxytyrosol contents reaching up to three times reported values. Mouthfeel attributes astringency, leafy taste, flavor and body, and persistency showed significant correlation with untargeted features. Supervised model-based analyses of the metabolome effectively discriminate wines from distinct genetic origins.CONCLUSION: Taken together, the results demonstrate the potential of novel grapevine genotypes to a more sustainable viticulture and quality wine production in warm climates. Comprehensive metabolite profiling of the wines reveals that genotype clustering is dependent on the chemical class and that traits not submitted to selective pressure are also altered by breeding. Supervised multivariate models were effective to predict the genetic origin of the wines based on the metabolic profile, indicating the potential of the technique to identify biomarkers for wines from sustainable genotypes. © 2024 Society of Chemical Industry.PMID:39171419 | DOI:10.1002/jsfa.13832

Front Public Health. 2024 Aug 7;12:1386441. doi: 10.3389/fpubh.2024.1386441. eCollection 2024.ABSTRACTINTRODUCTION: Metal carpentry includes a wide range of work activities such as welding and cutting metallic components, use of solvents and paints. Therefore, the employees in these types of activities are mainly exposed to welding fumes and volatile organic solvents. Here, we present an NMR-based metabolomic approach for assessing urinary profiles of workers in the same company that are exposed to two different risk factors.METHODS: The study enrolled 40 male subjects exposed to welding fumes, 13 male subjects exposed to volatile organic compounds of a metal carpentry company, and 24 healthy volunteers. All samples were collected, in the middle of the working week at fast. Thirty-five urinary metabolites belonging to different chemical classes such as amino acids, organic acids and amines were identified and quantified. Results were processed by multivariate statistical analysis for identifying significant metabolites for each working group examined, compared to controls.RESULTS: Workers exposed to welding fumes displayed urinary increase in glutamine, tyrosine, taurine, creatine, methylguanidine and pseudouridine associated to oxidative impairment, while workers exposed to volatile organic compounds showed higher urinary levels of branched chain aminoacids.CONCLUSION: Our work identified specific urinary profile related to each occupational exposure, even if it is below the threshold limit values.PMID:39171307 | PMC:PMC11335539 | DOI:10.3389/fpubh.2024.1386441

Chin Med J Pulm Crit Care Med. 2023 Dec 8;1(4):223-230. doi: 10.1016/j.pccm.2023.10.001. eCollection 2023 Dec.ABSTRACTChronic obstructive pulmonary disease (COPD) is a chronic lung disease with limited airflow. COPD is characterized by chronic bronchitis and emphysema, and is often accompanied by malnutrition with fatigue, muscle weakness, and an increased risk of infection. Although the pulmonary function test is used as the gold criterion for diagnosing COPD, it is unable to identify early COPD or classify the subtypes, thereby impeding early intervention and the precise diagnosis of COPD. Recent evidence suggests that metabolic dysfunction, such as changes in lipids, amino acids, glucose, nucleotides, and microbial metabolites in the lungs and intestine, have a great potential for diagnosing COPD in the early stage. However, a comprehensive summary of these metabolites and their effects on COPD is still lacking. This review summarizes the metabolites that are changed in COPD and highlights some promising early diagnostic markers and therapeutic targets. We emphasize that intensified dietary management may be among the most feasible methods to improve metabolism in the body.PMID:39171278 | PMC:PMC11332835 | DOI:10.1016/j.pccm.2023.10.001

Int J Cardiol Heart Vasc. 2024 Jul 30;54:101477. doi: 10.1016/j.ijcha.2024.101477. eCollection 2024 Oct.ABSTRACTSepsis-induced cardiomyopathy (SIC) is a common and high-mortality complication among critically ill patients. Uncertainties persist regarding the pathogenesis, pathophysiology, and diagnosis of SIC, underscoring the necessity to investigate potential biological mechanisms. With the rise of omics technologies, leveraging their high throughput and big data advantages, a systems biology perspective is employed to study the biological processes of SIC. This approach aids in gaining a better understanding of the disease's onset, progression, and outcomes, ultimately providing improved guidance for clinical practices. This review summarizes the currently applied omics technologies, omics studies related to SIC, and relevant omics databases.PMID:39171080 | PMC:PMC11334652 | DOI:10.1016/j.ijcha.2024.101477

Front Plant Sci. 2024 Aug 7;15:1447860. doi: 10.3389/fpls.2024.1447860. eCollection 2024.ABSTRACTINTRODUCTION: Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. cucumerinum (Foc) is a destructive soil-borne disease in cucumber (Cucumis sativus. L). However, there remains limited knowledge on the molecular mechanisms underlying FW resistance-mediated defense responses in cucumber.METHODS: In this study, metabolome and transcriptome profiling were carried out for two FW resistant (NR) and susceptible (NS), near isogenic lines (NILs) before and after Foc inoculation. NILs have shown consistent and stable resistance in multiple resistance tests conducted in the greenhouse and in the laboratory. A widely targeted metabolomic analysis identified differentially accumulated metabolites (DAMs) with significantly greater NR accumulation in response to Foc infection, including many phenolic acid and flavonoid compounds from the flavonoid biosynthesis pathway.RESULTS: Transcriptome analysis identified differentially expressed genes (DEGs) between the NILs upon Foc inoculation including genes for secondary metabolite biosynthesis and transcription factor genes regulating the flavonoid biosynthesis pathway. Joint analysis of the metabolomic and transcriptomic data identified DAMs and DEGs closely associated with the biosynthesis of phenolic acid and flavonoid DAMs. The association of these compounds with NR-conferred FW resistance was exemplified by in vivo assays. These assays found two phenolic acid compounds, bis (2-ethylhexyl) phthalate and diisooctyl phthalate, as well as the flavonoid compound gallocatechin 3-O-gallate to have significant inhibitory effects on Foc growth. The antifungal effects of these three compounds represent a novel finding.DISCUSSION: Therefore, phenolic acids and flavonoids play important roles in NR mediated FW resistance breeding in cucumber.PMID:39170788 | PMC:PMC11335689 | DOI:10.3389/fpls.2024.1447860

ACS Food Sci Technol. 2024 Jul 22;4(8):1937-1949. doi: 10.1021/acsfoodscitech.4c00298. eCollection 2024 Aug 16.ABSTRACTWe report the development of MagMet-W (magnetic resonance for metabolomics of wine), a software program that can automatically determine the chemical composition of wine via 1H nuclear magnetic resonance (NMR) spectroscopy. MagMet-W is an extension of MagMet developed for the automated metabolomic analysis of human serum by 1H NMR. We identified 70 compounds suitable for inclusion into MagMet-W. We then obtained 1D 1H NMR reference spectra of the pure compounds at 700 MHz and incorporated these spectra into the MagMet-W compound library. The processing of the wine NMR spectra and profiling of the 70 wine compounds were then optimized based on manual 1H NMR analysis. MagMet-W can automatically identify 70 wine compounds in most wine samples and can quantify them to 10-15% of the manually determined concentrations, and it can analyze multiple spectra simultaneously, at 10 min per spectrum. The MagMet-W Web server is available at https://www.magmet.ca.PMID:39170760 | PMC:PMC11334181 | DOI:10.1021/acsfoodscitech.4c00298

Front Vet Sci. 2024 Aug 7;11:1411520. doi: 10.3389/fvets.2024.1411520. eCollection 2024.ABSTRACTINTRODUCTION: Despite the absence of definitive evidence indicating that the cp4-epsps gene and its resultant recombinant proteins have significant harmful effects on either human or animal health, the safety assessment of genetically modified (GM) crops expressing the CP4-EPSPS proteins has been controversial. This study endeavor was aimed at evaluating the potential risks posed by the CP4-EPSPS protein in transgenic crops, thereby contributing to the advancement of risk assessment methodologies in the context of genetically engineered crops.METHODS: To ascertain the appropriate daily dosages for oral gavage administration, the expression levels of the CP4-EPSPS protein in a recombinant yeast were quantified. Subsequently, physiological and biochemical analysis, metabolomics, and metagenomic analysis were conducted based on a 90-day Sprague-Dawley (SD) rats feeding experiment, respectively, thereby enhancing the depth and precision of our risk assessment framework.RESULTS: The results from the physiological and biochemical analysis, organ pathological, blood metabolism, gut microbiota, and correlation analysis of metabolites and gut microbiota revealed several biomarkers for further risk assessment. These biomarkers include clinical biochemical indexes such as total bilirubin (TBIL), direct bilirubin (DBIL), creatine kinase (CK), and lactate dehydrogenase (LDH); metabolites like Methionine, 2-Oxovaleric acid, and LysoPC (16:0); and gut microbiota including Blautia wexlerae, Holdemanella biformis, Dorea sp. CAG 317, Coriobacteriaceae and Erysipelotrichaceae.CONCLUSION: In conclusion, the risk can be significantly reduced by directly consuming inactivated recombinant CP4-EPSPS. Therefore, in everyday life, the risk associated with consuming GM foods containing recombinant CP4-EPSPS is substantially reduced after heat treatment.PMID:39170628 | PMC:PMC11335726 | DOI:10.3389/fvets.2024.1411520

Heliyon. 2024 Aug 5;10(15):e35491. doi: 10.1016/j.heliyon.2024.e35491. eCollection 2024 Aug 15.ABSTRACTAs a classical traditional Chinese patent medicine, Shugan Yipi Granule is widely used in China to treat non-alcoholic fatty liver disease (NAFLD) recently. Our previous study confirmed that Shugan Yipi Granule are effective in NAFLD. However, its underlying mechanism is still unknown. This study aims to investigate the mechanism of Shugan Yipi Granule on NAFLD based on network pharmacology prediction, liquid chromatography-mass spectrometry (LC-MS) analysis and in vitro verification. We obtained the active ingredients and targets of Shugan Yipi Granule and NAFLD from 6 traditional Chinese medicine databases, and the crucial components and targets screened by protein-protein interaction (PPI) network were used for molecular docking. Plasma metabolomics of NAFLD patients treated with Shugan Yipi Granule for one month was analyzed using LC-MS methods and MetaboAnalyst 4.0 to obtain significant differential metabolites and pathways. Finally, free fatty acid (FFA) induced HepG2 cells were treated with different concentrations of quercetin and kaempferol, then oil red o (ORO) and triglyceride (TG) level were tested to verify the lipid deposition of the cell. Network pharmacology analysis showed that the main active ingredients of Shugan Yipi Granule include quercetin, kaempferol and other 58 ones, as well as 188 potential targets. PI3K/Akt signaling pathway was found to be the most relevant pathway for the treatment of NAFLD. Non-targeted metabolomics showed that quercetin and kaempferol were significantly up-regulated differential metabolites and were involved in metabolic pathways such as thyroid hormone signaling. In vitro results showed that quercetin, kaempferol were effective in reducing lipid deposition and TG content by inhibiting cellular fatty acid uptake. Ultimately, with the network pharmacology and serum metabolomics analysis, quercetin and kaempferol were found to be the important active ingredients and significantly up-regulated differential metabolites of Shugan Yipi Granule against NAFLD, which we inferred that they may regulate NAFLD through PI3K/Akt signaling pathway and thyroid hormone metabolism pathway. The in vitro experiment verification results showed that quercetin and kaempferol attenuated the lipid accumulation and TG content by inhibiting the fatty acid uptake in the FFA-induced HepG2 cell. Current study provides the necessary experimental basis for subsequent in-depth mechanism research.PMID:39170438 | PMC:PMC11336705 | DOI:10.1016/j.heliyon.2024.e35491

Heliyon. 2024 Jul 30;10(15):e35443. doi: 10.1016/j.heliyon.2024.e35443. eCollection 2024 Aug 15.ABSTRACTCOVID-19 is a highly contagious infectious disease that has posed a global threat, leading to a widespread pandemic characterized by multi-organ complications and failures.AIMS: The present study was conducted to evaluate the impact of Pfizer and Sinopharm vaccines on metabolomic changes and their correlations with immune pathways.MAIN METHODS: The study used a cross-sectional design and implemented an untargeted metabolomics-based approach. Plasma samples were obtained from three groups: non-vaccinated participants, Sinopharm-vaccinated participants, and Pfizer-vaccinated participants. Comparative metabolomic analysis was conducted using TIMS-QTOF, and multiple t-tests with a 5 % false discovery rate (FDR) were performed using MetaboAnalyst software.KEY FINDINGS: Out of the 105 metabolites detected, 72 showed statistically significant changes (p-value < 0.05) across the different groups. Notably, several metabolites such as neopterin, pyridoxal, and syringic acid were markedly altered in individuals vaccinated with Pfizer. Conversely, in the Sinopharm-vaccinated group, significant alterations were observed in sphinganine, neopterin, and sphingosine. These metabolites hold potential as biomarkers for evaluating vaccine efficacy. Additionally, both Pfizer and Sinopharm vaccinations were found to influence sphingolipid and histidine metabolisms compared to the control group. The Sinopharm group also displayed changes in lysine degradation relative to the control group. When comparing the enriched pathways between the Pfizer and Sinopharm-vaccinated groups, differences were observed in purine metabolism. Furthermore, alterations in tryptophan and vitamin B6 metabolism were noted when comparing the Pfizer-vaccinated group with both the control and Sinopharm-vaccinated groups.SIGNIFICANCE: These findings highlight the importance of metabolomics in assessing vaccine effectiveness and identifying potential biomarkers for monitoring the efficacy of newly developed vaccines in a shorter timeframe.PMID:39170395 | PMC:PMC11336712 | DOI:10.1016/j.heliyon.2024.e35443

Heliyon. 2024 Jul 20;10(15):e34917. doi: 10.1016/j.heliyon.2024.e34917. eCollection 2024 Aug 15.ABSTRACTBACKGROUND: This study aimed to investigate the effect of eight weeks of high-intensity interval training (HIIT) on muscle metabolism in rats with type 2 diabetes (T2D) using metabolomics approaches.METHODS: 20 male Wistar rats at the age of 8 weeks-were assigned to four groups of five, each in the group randomly: control (CTL), type 2 diabetes (DB), HIIT (EX), and type 2 diabetes + HIIT (DBX). T2D was induced by two months of a high-fat diet plus a single dose of streptozotocin (35 mg/kg). Rats in the EX and DBX groups performed eight weeks of HIIT (running at 80-100 % of Vmax, 4-10 intervals). NMR spectroscopy was used to determine the changes in the muscle metabolome profile after training.RESULTS: Changes in metabolite abundance following exercise revealed distinct clustering in multivariate analysis. The essential metabolite changes between the DB and CTL groups were arginine metabolism, purine metabolism, phosphate pathway, amino sugar metabolism, glutathione metabolism, and aminoacyl-tRNA biosynthesis. However, Arginine biosynthesis, pyrimidine metabolism, aminoacyl-tRNA biosynthesis, and alanine, aspartate, and glutamate metabolism were altered between the DBX and DB groups.CONCLUSION: These results suggest that eight weeks of HIIT could reverse metabolic changes induced by T2D in rat muscles, contributing to reduced FBG and HOMA-IR levels.PMID:39170342 | PMC:PMC11336285 | DOI:10.1016/j.heliyon.2024.e34917