PubMed

PNAS Nexus. 2023 Oct 31;2(10):pgad326. doi: 10.1093/pnasnexus/pgad326. eCollection 2023 Oct.ABSTRACTPlants produce specialized metabolites with defensive properties that are often synthesized through the coordinated regulation of metabolic genes by transcription factors in various biological contexts. In this study, we investigated the regulatory function of the transcription factor PhERF1 from petunia (Petunia hybrida), which belongs to a small group of ETHYLENE RESPONSE FACTOR (ERF) family members that regulate the biosynthesis of bioactive alkaloids and terpenoids in various plant lineages. We examined the effects of transiently overexpressing PhERF1 in petunia leaves on the transcriptome and metabolome, demonstrating the production of a class of specialized steroids, petuniolides, and petuniasterones in these leaves. We also observed the activation of many metabolic genes, including those involved in sterol biosynthesis, as well as clustered genes that encode new metabolic enzymes, such as cytochrome P450 oxidoreductases, 2-oxoglutarate-dependent dioxygenases, and BAHD acyltransferases. Furthermore, we determined that PhERF1 transcriptionally induces downstream metabolic genes by recognizing specific cis-regulatory elements in their promoters. This study highlights the potential of evolutionarily conserved transcriptional regulators to induce the production of specialized products through transcriptional reprogramming.PMID:37920550 | PMC:PMC10619512 | DOI:10.1093/pnasnexus/pgad326

Heliyon. 2023 Oct 21;9(11):e21392. doi: 10.1016/j.heliyon.2023.e21392. eCollection 2023 Nov.ABSTRACTImproved biosynthesis of commercially and pharmacologically relevant phytometabolites through genetic and metabolic engineering is a lucrative strategy for crop improvement. However, identifying appropriate biosynthetic pathways pertaining to specific bioactivities has been challenging since the major metabolic pathways remain closely interconnected. Here we propose a reverse association strategy in which, based on the phytochemical profile, putative target metabolic pathways could be identified for increased production of phytochemicals. Dried seed fruits of Coriandrum sativum, Trachyspermum ammi, Cuminum cyminum, and Foeniculum vulgare (family Apiaceae) were subjected to untargeted gas chromatography-mass spectrometry-based phytochemical profiling followed by evaluation of the overall antioxidant profile using multiple antioxidant assays. Using bioinformatics approaches, specific phytochemical classes and the enrichment of their respective biosynthetic pathways were identified. Collectively, the data suggest enrichment of isoprenoids and fatty acids biosynthetic pathways. The close association of metabolic pathways with antioxidant capacities indicated a need for enrichment of specific yet closely-related metabolic pathways to achieve an improved quality of spices for better antioxidant effects.PMID:37920519 | PMC:PMC10618831 | DOI:10.1016/j.heliyon.2023.e21392

Heliyon. 2023 Oct 19;9(11):e21011. doi: 10.1016/j.heliyon.2023.e21011. eCollection 2023 Nov.ABSTRACTAging is associated with gradual changes in liver structure, altered metabolites and other physiological/pathological functions in hepatic cells. However, its characterized phenotypes based on altered metabolites and the underlying biological mechanism are unclear. Advancements in high-throughput omics technology provide new opportunities to understand the pathological process of aging. Here, in our present study, both metabolomics and phosphoproteomics were applied to identify the altered metabolites and phosphorylated proteins in liver of young (the WTY group) and naturally aged (the WTA group) mice, to find novel biomarkers and pathways, and uncover the biological mechanism. Analysis showed that the body weights, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the WTA group. The grips decreased with age, while the triglyceride (TG) and cholesterol (TC) did not change significantly. The increase of fibrosis, accumulation of inflammatory cells, hepatocytes degeneration, the deposition of lipid droplets and glycogen, the damaged mitochondria, and deduction of endoplasmic reticulum were observed in the aging liver under optical and electron microscopes. In addition, a network of metabolites and phosphorylated proteomes of the aging liver was established. Metabolomics detected 970 metabolites in the positive ion mode and 778 metabolites in the negative ion mode. A total of 150 pathways were pooled. Phosphoproteomics identified 2618 proteins which contained 16621 phosphosites. A total of 164 pathways were detected. 65 common pathways were detected in two omics. Phosphorylated protein heat shock protein HSP 90-alpha (HSP90A) and v-raf murine viral oncogene homolog B1(BRAF), related to cancer pathway, were significantly upregulated in aged mice liver. Western blot verified that protein expression of MEK and ERK, downstream of BRAF pathway were elevated in the liver of aging mice. However, the protein expression of BRAF was not a significant difference. Overall, these findings revealed a close link between aging and cancer and contributed to our understanding of the multi-omics changes in natural aging.PMID:37920504 | PMC:PMC10618800 | DOI:10.1016/j.heliyon.2023.e21011

Food Chem X. 2023 Oct 21;20:100952. doi: 10.1016/j.fochx.2023.100952. eCollection 2023 Dec 30.ABSTRACTTo interpret the formation characteristic flavor during oolong tea manufacturing process, the dynamic changes of key flavor components in samples from various processing steps of Tieguanyin oolong tea production were investigated using widely-targeted metabolomic and the transcriptomic approaches. As a result, a total of 1078 metabolites were determined, of which 62 compounds were identified as biomarkers significantly changed over the manufacturing process. Quantitative determination of the total 50,343 transcripts showed 7480 of them were co-expressed different genes. Glutamic acid served as a critical metabolism hub and a signaling molecule for diverse stress responses. Additionally, the targeted quantification results showed that the contents of catechins and xanthine alkaloids in dried tea were dramatically decreased by 20.19% and 7.15% respectively than those in fresh leaves, which potentially contributed to the alleviation of astringent or bitter palates, promoting the characteristic mellow and rich flavor of Tieguanyin oolong tea.PMID:37920364 | PMC:PMC10618703 | DOI:10.1016/j.fochx.2023.100952

Front Microbiol. 2023 Oct 18;14:1286661. doi: 10.3389/fmicb.2023.1286661. eCollection 2023.ABSTRACTBACKGROUND: The use of omics data for monitoring the microbial flow of fresh meat products along a production line and the development of spoilage prediction tools from these data is a promising but challenging task. In this context, we produced a large multivariate dataset (over 600 samples) obtained on the production lines of two similar types of fresh meat products (poultry and raw pork sausages). We describe a full analysis of this dataset in order to decipher how the spoilage microbial ecology of these two similar products may be shaped differently depending on production parameter characteristics.METHODS: Our strategy involved a holistic approach to integrate unsupervised and supervised statistical methods on multivariate data (OTU-based microbial diversity; metabolomic data of volatile organic compounds; sensory measurements; growth parameters), and a specific selection of potential uncontrolled (initial microbiota composition) or controlled (packaging type; lactate concentration) drivers.RESULTS: Our results demonstrate that the initial microbiota, which is shown to be very different between poultry and pork sausages, has a major impact on the spoilage scenarios and on the effect that a downstream parameter such as packaging type has on the overall evolution of the microbial community. Depending on the process, we also show that specific actions on the pork meat (such as deboning and defatting) elicit specific food spoilers such as Dellaglioa algida, which becomes dominant during storage. Finally, ecological network reconstruction allowed us to map six different metabolic pathways involved in the production of volatile organic compounds involved in spoilage. We were able connect them to the different bacterial actors and to the influence of packaging type in an overall view. For instance, our results demonstrate a new role of Vibrionaceae in isopropanol production, and of Latilactobacillus fuchuensis and Lactococcus piscium in methanethiol/disylphide production. We also highlight a possible commensal behavior between Leuconostoc carnosum and Latilactobacillus curvatus around 2,3-butanediol metabolism.CONCLUSION: We conclude that our holistic approach combined with large-scale multi-omic data was a powerful strategy to prioritize the role of production parameters, already known in the literature, that shape the evolution and/or the implementation of different meat spoilage scenarios.PMID:37920261 | PMC:PMC10619683 | DOI:10.3389/fmicb.2023.1286661

Front Pharmacol. 2023 Oct 18;14:1258138. doi: 10.3389/fphar.2023.1258138. eCollection 2023.ABSTRACTIn this study, we have employed metabolomics technology in combination with network pharmacology to ascertain the key metabolites and hub genes. The objective was to explore the pathway of Qibai Pingfei Capsule (QBPF) in treating COPD through metabolomics. We identified 96 differential metabolites in the lung tissues of rats belonging to control and model groups, out of which 47 were observed to be critical (VIP >2, p < 0.05). Furthermore, 16 important differential metabolites were reversed after QBPF treatment. Using network pharmacology, we identified 176 core targets of 81 drug-active ingredients. Our comprehensive analysis of network pharmacology and metabolomics enabled us to identify a core target, prostaglandin-endoperoxide synthase 2 (PTGS2), and a core metabolic pathway for glutathione metabolism. Finally, the result of molecular docking showed that PTGS2 had strong binding activity to 18 compounds including Fumarine and Kaempferol, etc.. PTGS2 is a marker of ferroptosis, so we wanted to explore whether QBPF could inhibit ferroptosis in COPD. The results showed that ferroptosis was involved in the pathogenesis of COPD, and QBPF could inhibit the occurrence of ferroptosis. In conclusion, the mechanism of QBPF for treating COPD may be related to PTGS2 expression, glutathione metabolism and ferroptosis.PMID:37920214 | PMC:PMC10618342 | DOI:10.3389/fphar.2023.1258138

Front Cardiovasc Med. 2023 Oct 18;10:1304680. doi: 10.3389/fcvm.2023.1304680. eCollection 2023.NO ABSTRACTPMID:37920177 | PMC:PMC10619719 | DOI:10.3389/fcvm.2023.1304680

J Transl Med. 2023 Nov 2;21(1):776. doi: 10.1186/s12967-023-04637-y.ABSTRACTBACKGROUND: Viral and autoimmune encephalitis may present with similar symptoms, but require different treatments. Thus, there is a need for biomarkers to improve diagnosis and understanding of pathogenesis. We hypothesized that virus-host cell interactions lead to different changes in central nervous system (CNS) metabolism than autoimmune processes and searched for metabolite biomarkers in cerebrospinal fluid (CSF) to distinguish between the two conditions.METHODS: We applied a targeted metabolomic/lipidomic analysis to CSF samples from patients with viral CNS infections (n = 34; due to herpes simplex virus [n = 9], varicella zoster virus [n = 15], enteroviruses [n = 10]), autoimmune neuroinflammation (n = 25; autoimmune anti-NMDA-receptor encephalitis [n = 8], multiple sclerosis [n = 17), and non-inflamed controls (n = 31; Gilles de la Tourette syndrome [n = 20], Bell's palsy with normal CSF cell count [n = 11]). 85 metabolites passed quality screening and were evaluated as biomarkers. Standard diagnostic CSF parameters were assessed for comparison.RESULTS: Of the standard CSF parameters, the best biomarkers were: CSF cell count for viral infections vs. controls (area under the ROC curve, AUC = 0.93), Q-albumin for viral infections vs. autoimmune neuroinflammation (AUC = 0.86), and IgG index for autoimmune neuroinflammation vs. controls (AUC = 0.90). Concentrations of 2 metabolites differed significantly (p < 0.05) between autoimmune neuroinflammation and controls, with proline being the best biomarker (AUC = 0.77). In contrast, concentrations of 67 metabolites were significantly higher in viral infections than controls, with SM.C16.0 being the best biomarker (AUC = 0.94). Concentrations of 68 metabolites were significantly higher in viral infections than in autoimmune neuroinflammation, and the 10 most accurate metabolite biomarkers (AUC = 0.89-0.93) were substantially better than Q-albumin (AUC = 0.86). These biomarkers comprised six phosphatidylcholines (AUC = 0.89-0.92), two sphingomyelins (AUC = 0.89, 0.91), and acylcarnitines isobutyrylcarnitine (C4, AUC = 0.92) and isovalerylcarnitine (C5, AUC = 0.93). Elevated C4 and C5 concentrations suggested dysfunctional mitochondrial β-oxidation and correlated only moderately with CSF cell count (Spearman ρ = 0.41 and 0.44), indicating that their increase is not primarily driven by inflammation.CONCLUSIONS: Changes in CNS metabolism differ substantially between viral CNS infections and autoimmune neuroinflammation and reveal CSF metabolites as pathophysiologically relevant diagnostic biomarkers for the differentiation between the two conditions. In viral CNS infections, the observed higher concentrations of free phospholipids are consistent with disruption of host cell membranes, whereas the elevated short-chain acylcarnitines likely reflect compromised mitochondrial homeostasis and energy generation.PMID:37919735 | DOI:10.1186/s12967-023-04637-y

Front Zool. 2023 Nov 2;20(1):35. doi: 10.1186/s12983-023-00513-z.ABSTRACTExtreme environmental conditions at high altitude, such as hypobaric hypoxia, low temperature, and strong UV radiation, pose a great challenge to the survival of animals. Although the mechanisms of adaptation to high-altitude environments have attracted much attention for native plateau species, the underlying metabolic regulation remains unclear. Here, we used a multi-platform metabolomic analysis to compare metabolic profiles of liver between high- and low-altitude populations of toad-headed lizards, Phrynocephalus vlangalii, from the Qinghai-Tibet Plateau. A total of 191 differential metabolites were identified, consisting of 108 up-regulated and 83 down-regulated metabolites in high-altitude lizards as compared with values for low-altitude lizards. Pathway analysis revealed that the significantly different metabolites were associated with carbohydrate metabolism, amino acid metabolism, purine metabolism, and glycerolipid metabolism. Most intermediary metabolites of glycolysis and the tricarboxylic acid cycle were not significantly altered between the two altitudes, but most free fatty acids as well as β-hydroxybutyric acid were significantly lower in the high-altitude population. This may suggest that high-altitude lizards rely more on carbohydrates as their main energy fuel rather than lipids. Higher levels of phospholipids occurred in the liver of high-altitude populations, suggesting that membrane lipids may undergo adaptive remodeling in response to low-temperature stress at high altitude. In summary, this study demonstrates that metabolic profiles differ substantially between high- and low-altitude lizard populations, and that these differential metabolites and metabolic pathways can provide new insights to reveal mechanisms of adaptation to extreme environments at high altitude.PMID:37919723 | DOI:10.1186/s12983-023-00513-z

BMC Emerg Med. 2023 Nov 3;23(1):128. doi: 10.1186/s12873-023-00891-x.ABSTRACTOBJECTIVES: We aim to understand the current situation of the first aid ability and training needs of Chinese medical personnel to provide a scientific basis for formulating the contents and methods of emergency medical rescue training and thereby improve the first aid level of Chinese medical personnel.METHODS: A cross-sectional survey was conducted between June 2022 and February 2023 using a two-stage cluster sampling method with a structured questionnaire sent to medical workers in 12 provinces in China. 14,527 questionnaires were included in this study. Data were collected on demographic characteristics, first aid knowledge and skills, and training needs. Variance analysis was used to compare the difference between the first aid ability and training needs of medical staff in different hospitals, and multiple linear regression analysis was carried out to evaluate first aid ability and training needs.RESULT: The study included 6041 patients (41.6%) in tertiary hospitals, 5838 patients (40.2%) in secondary hospitals, and 2648 patients (18.2%) in primary hospitals. There were significant differences in the first aid ability and training needs of medical staff in hospitals of different levels (p < 0.001). The score of first aid knowledge and skills in tertiary hospitals was the highest (209.7 ± 45.0), and the score of training needs in primary hospitals was the highest (240.6 ± 44.0). There was a significant correlation between first aid ability and training needs score (p < 0.001). Multiple linear regression analysis shows that geographic region, age, work tenure, gender, job title, department, professional title, monthly income, and hospital level are the influencing factors of training demand.CONCLUSION: Medical staff in primary hospitals generally have low first aid knowledge and skills and a strong willingness to train. Therefore, it is imperative to strengthen the training of first aid ability and research training strategies. The level of the hospital is closely related to the level of first aid, so it is necessary to recognize the commonalities and differences in medical staff's demand for first aid knowledge and skills and carry out targeted education and training.PMID:37919639 | DOI:10.1186/s12873-023-00891-x

Planta. 2023 Nov 3;258(6):111. doi: 10.1007/s00425-023-04258-1.ABSTRACTRole of salinity responsive metabolites of rice and its wild species has been discussed. Salinity stress is one of the important environmental stresses that severely affects rice productivity. Although, several vital physio-biochemical and molecular responses have been activated in rice under salinity stress which were well described in literatures, the mechanistic role of salt stress and microbes-induced metabolites to overcome salt stress in rice are less studied. Nevertheless, over the years, metabolomic studies have allowed a comprehensive analyses of rice salt stress responses. Hence, we review the salt stress-triggered alterations of various metabolites in rice and discuss their significant roles toward salinity tolerance. Some of the metabolites such as serotonin, salicylic acid, ferulic acid and gentisic acid may act as signaling molecules to activate different downstream salt-tolerance mechanisms; whereas, the other compounds such as amino acids, sugars and organic acids directly act as protective agents to maintain osmotic balance and scavenger of reactive oxygen species during the salinity stress. The quantity, type, tissues specificity and time of accumulation of metabolites induced by salinity stress vary between salt-sensitive and tolerant rice genotypes and thus, contribute to their different degrees of salt tolerance. Moreover, few tolerance metabolites such as allantoin, serotonin and melatonin induce unique pathways for activation of defence mechanisms in salt-tolerant varieties of rice, suggesting their potential roles as the universal biomarkers for salt tolerance. Therefore, these metabolites can be applied exogenously to the sensitive genotypes of rice to enhance their performance under salt stress. Furthermore, the microbes of rhizosphere also participated in rice salt tolerance either directly or indirectly by regulating their metabolic pathways. Thus, this review for the first time offers valuable and comprehensive insights into salt-induced spatio-temporal and genotype-specific metabolites in different genotypes of rice which provide a reference point to analyze stress-gene-metabolite relationships for the biomarker designing in rice. Further, it can also help to decipher several metabolic systems associated with salt tolerance in rice which will be useful in developing salt-tolerance cultivars by conventional breeding/genetic engineering/exogenous application of metabolites.PMID:37919614 | DOI:10.1007/s00425-023-04258-1

NPJ Precis Oncol. 2023 Nov 2;7(1):114. doi: 10.1038/s41698-023-00434-4.ABSTRACTMolecular subtyping of lung squamous cell carcinoma (LUSC) has been performed at the genomic, transcriptomic, and proteomic level. However, LUSC stratification based on tissue metabolomics is still lacking. Combining high-mass-resolution imaging mass spectrometry with consensus clustering, four tumor- and four stroma-specific subtypes with distinct metabolite patterns were identified in 330 LUSC patients. The first tumor subtype T1 negatively correlated with DNA damage and immunological features including CD3, CD8, and PD-L1. The same features positively correlated with the tumor subtype T2. Tumor subtype T4 was associated with high PD-L1 expression. Compared with the status of subtypes T1 and T4, patients with subtype T3 had improved prognosis, and T3 was an independent prognostic factor with regard to UICC stage. Similarly, stroma subtypes were linked to distinct immunological features and metabolic pathways. Stroma subtype S4 had a better prognosis than S2. Subsequently, analyses based on an independent LUSC cohort treated by neoadjuvant therapy revealed that the S2 stroma subtype was associated with chemotherapy resistance. Clinically relevant patient subtypes as determined by tissue-based spatial metabolomics are a valuable addition to existing molecular classification systems. Metabolic differences among the subtypes and their associations with immunological features may contribute to the improvement of personalized therapy.PMID:37919427 | DOI:10.1038/s41698-023-00434-4

BMJ Open. 2023 Nov 2;13(11):e072024. doi: 10.1136/bmjopen-2023-072024.ABSTRACTINTRODUCTION: Imprecise nutritional recommendations due to a lack of diagnostic test accuracy are a frequent problem for individuals with adverse reactions to foods but no precise diagnosis. Consequently, patients follow very broad and strict elimination diets to avoid uncontrolled symptoms such as diarrhoea and abdominal pain. Dietary limitations and the uncertainty of developing gastrointestinal symptoms after the inadvertent ingestion of food have been demonstrated to reduce the quality of life (QoL) of affected individuals and subsequently might increase the risk of malnutrition and intestinal dysbiosis. This trial aims to investigate the effects of a tailored diet based on the confocal laser endoscopy (CLE) examination result to limit the side effects of unspecific and broad elimination diets and to increase the patient's QoL.METHODS AND ANALYSIS: The study is designed as a prospective, double-blind, monocentric, randomised and controlled trial conducted at the University Hospital of Schleswig-Holstein, Campus Lübeck, Germany. One hundred seventy-two patients with non-IgE-related food allergies and positive CLE results will be randomised to either a tailored diet or a standard fivefold elimination diet. The primary endpoints are the difference between the end and the start of the intervention in health-related QoL and the sum score of the severity of symptoms after 12 weeks. Key secondary endpoints are changes in the severity of symptoms, further QoL measurements, self-assessed state of health and number of days with a pathologically altered stool. Microbiome diversity and metabolome of stool, urine and blood will also be investigated. Safety endpoints are body composition, body mass index and adverse events.ETHICS AND DISSEMINATION: The study protocol was accepted by the ethical committee of the University of Lübeck (AZ: 22-111) on 4 May2022. Results of the study will be published in peer-reviewed journals and presented at scientific meetings.TRIAL REGISTRATION NUMBER: German Clinical Trials Register (DRKS00029323).PMID:37918930 | DOI:10.1136/bmjopen-2023-072024

J Nutr. 2023 Oct 31:S0022-3166(23)72678-3. doi: 10.1016/j.tjnut.2023.10.024. Online ahead of print.ABSTRACTBACKGROUND: Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of compounds which may provide cardiometabolic benefits.OBJECTIVE: We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention. Associations between changes in salmon FSCs and changes in cardiometabolic health indicators (CHIs) were also explored.METHODS: For this secondary analysis of a randomized, crossover, controlled feeding trial, 41 participants consumed MED diets with two servings of salmon per week for two five-week periods. CHIs were assessed and fasting plasma was collected pre- and post-intervention. Plasma, salmon, and 99 MED foods were analyzed using liquid chromatography mass spectrometry-based metabolomics. Compounds were characterized as salmon FSCs if detected in all salmon replicates but none of the other foods. Metabolites of salmon FSCs were predicted using machine learning. For salmon FSCs and metabolites found in plasma, linear mixed-effect models were used to assess change from pre- to post-intervention and associations with changes in CHIs.RESULTS: Relative to the other 99 MED foods, there were 508 salmon FSCs with 237 unique metabolites. A total of 143 salmon FSCs and 106 metabolites were detected in plasma. Forty-eight salmon FSCs and 30 metabolites increased after the intervention (FDR<0.05). Increases in two annotated salmon FSCs and two metabolites were associated with improvements CHIs, including total cholesterol, LDL cholesterol, triglycerides, and Apolipoprotein B.CONCLUSIONS: A data-driven nutrimetabolomics strategy identified salmon FSCs and their predicted metabolites that were detectable in plasma and changed after consumption of a salmon-containing MED diet. Findings support this approach for discovery of compounds in foods that may serve, upon further validation, as biomarkers or act as bioactive components influential to health.CLINICAL TRIAL REGISTRY NUMBER: NCT02573129 (original Mediterranean-style diet intervention); NCT05500976 (ongoing clinical trial).PMID:37918675 | DOI:10.1016/j.tjnut.2023.10.024

Metab Eng. 2023 Oct 31:S1096-7176(23)00145-3. doi: 10.1016/j.ymben.2023.10.005. Online ahead of print.ABSTRACTFor engineered microorganisms, the production of heterologous proteins that are often useless to host cells represents a burden on resources, which have to be shared with normal cellular processes. Within a certain metabolic leeway, this competitive process has no impact on growth. However, once this leeway, or free capacity, is fully utilized, the extra load becomes a metabolic burden that inhibits cellular processes and triggers a broad cellular response, reducing cell growth and often hindering the production of heterologous proteins. In this study, we sought to characterize the metabolic rearrangements occurring in the central metabolism of Pseudomonas putida at different levels of metabolic load. To this end, we constructed a P. putida KT2440 strain that expressed two genes encoding fluorescent proteins, one in the genome under constitutive expression to monitor the free capacity, and the other on an inducible plasmid to probe heterologous protein production. We found that metabolic fluxes are considerably reshuffled, especially at the level of periplasmic pathways, as soon as the metabolic load exceeds the free capacity. Heterologous protein production leads to the decoupling of anabolism and catabolism, resulting in large excess energy production relative to the requirements of protein biosynthesis. Finally, heterologous protein production was found to exert a stronger control on carbon fluxes than on energy fluxes, indicating that the flexible nature of P. putida's central metabolic network is solicited to sustain energy production.PMID:37918614 | DOI:10.1016/j.ymben.2023.10.005

Int J Biol Macromol. 2023 Oct 31:127718. doi: 10.1016/j.ijbiomac.2023.127718. Online ahead of print.ABSTRACTIn this study, the nano-assemblies of bovine casein hydrolyzed peptides (HP) modified by fatty acids with various alkyl chain lengths (C8, C10, C12 and C14) were synthesized. The physicochemical properties of HP-C8-HP-C14 nano-assemblies were characterized using spectra, laser particle size analyzer, contact angle meter, scanning electron microscope (SEM) and cryo-transmission electron microscope (Cryo-TEM). HP-C8 and HP-C10 self-assembled into a hollow cube cage with an average size of ~500 nm, and the assembly of HP-C12 showed a flower-shaped morphology with more dispersed behavior, and droplet size was observed as ~20 nm. The in vitro cytotoxicity against human breast cancer cells MCF-7 was tested using CCK-8 assay and flow cytometry analysis. HP-C12 showed the highest cytotoxicity for MCF-7 cells with an inhibition rate of 66.03 % ± 0.35 % with an IC50 value of 7.4 μM among HP-Cn. HP-C8, HP-C10 and HP-C12 significantly affected on the migration, invasion and apoptosis of MCF-7 cells. The apoptosis mechanism may depend on the upregulation of anti-apoptotic protein Bcl-2 as well as pro-apoptotic proteins Bax and caspase-8. The dead MCF-7 cells were analyzed with UHPLC-MS/MS using untargeted metabolomics, revealing key metabolic pathways.PMID:37918594 | DOI:10.1016/j.ijbiomac.2023.127718

Chemosphere. 2023 Oct 31:140587. doi: 10.1016/j.chemosphere.2023.140587. Online ahead of print.ABSTRACTAntibiotic residues can reach aquatic ecosystems through urban wastewater discharges, posing an ecotoxicological risk for aquatic organisms and favoring the development of bacterial resistance. To assess the emission rate and hazardousness of these compounds, it is important to carry out periodic chemical monitoring campaigns that provide information regarding the actual performance of wastewater treatment plants (WWTPs) and the potential impact of the treated wastewater in the aquatic environment. In this study, 18 of the most widely consumed antibiotics in Spain were determined by liquid chromatography-tandem mass spectrometry in both influent (IWW) and effluent wastewater (EWW) samples collected over four seasons along 2021-2022. Eleven antibiotics were detected in EWW with azithromycin, ciprofloxacin and levofloxacin showing the highest concentration levels (around 2 μg L-1 of azithromycin and 0.4 μg L-1 of quinolone compounds). Data showed that only 4 out of the 11 compounds were removed by more than 50 % in the WWTP, with sulfamethoxazole standing out with an average removal efficiency >80 %. The risk that treated water could pose to the aquatic environment was also assessed, with 6 compounds indicating a potential environmental risk by exceeding established ecotoxicological and resistance thresholds. Based on the risk assessment, the WWTP removal efficiency required to reduce such risk for antibiotics was estimated. In addition, pooled wastewater samples were screened by LC coupled to high resolution mass spectrometry with ion mobility separation, searching for metabolites and transformation products of the antibiotics investigated to widen future research. Studies like this are crucial to map the impact of antibiotic pollution and to provide the basis for designing water quality and risk prevention monitoring programs.PMID:37918528 | DOI:10.1016/j.chemosphere.2023.140587

Cell Rep. 2023 Oct 30:113336. doi: 10.1016/j.celrep.2023.113336. Online ahead of print.ABSTRACTAntiretroviral therapy (ART) has dramatically lengthened lifespan among people with HIV (PWH), but this population experiences heightened rates of inflammation-related comorbidities. HIV-associated inflammation is linked with an altered microbiome; whether such alterations precede inflammation-related comorbidities or occur as their consequence remains unknown. We find that ART-treated PWH exhibit depletion of gut-resident bacteria that produce short-chain fatty acids (SCFAs)-crucial microbial metabolites with anti-inflammatory properties. Prior reports establish that fecal SCFA concentrations are not depleted in PWH. We find that gut-microbiota-mediated SCFA production capacity is better reflected in serum than in feces and that PWH exhibit reduced serum SCFA, which associates with inflammatory markers. Leveraging stool and serum samples collected prior to comorbidity onset, we find that HIV-specific microbiome alterations precede morbidity and mortality in ART-treated PWH. Among these microbiome alterations, reduced microbiome-mediated conversion of lactate to propionate precedes mortality in PWH. Thus, gut microbial fiber/lactate conversion to SCFAs may modulate HIV-associated comorbidity risk.PMID:37918403 | DOI:10.1016/j.celrep.2023.113336

J Pharm Biomed Anal. 2023 Oct 30;238:115828. doi: 10.1016/j.jpba.2023.115828. Online ahead of print.ABSTRACTPterocephali Herba (PH), the dried whole plant of Pterocephalus hookeri, is a Tibetan medicine commonly used to treat rheumatoid arthritis (RA). Iridoids, triterpenoids, flavonoids and phenylpropanoids are the major groups of bioactive constituents from PH. However, only ursolic acid and oleanolic acid, two unspecific triterpenoid components, are used as markers for the quality control of PH in Chinese Pharmacopoeia. Herein, an UPLC-TQ-MS/MS integrating SIR and MRM mode method for simultaneously quantifying 18 components, i.e., 9 iridoids, 3 triterpenoids, 3 phenylpropanoids, 2 flavonoids and quinic acid, in PH was developed and validated, and was used to evaluate 10 batches of PH samples from different origins. Hierarchical cluster analysis (HCA) was used to show the clustering of PH samples, while spearman correlation analysis was adopted to evaluate the correlation between ursolic acid/oleanolic acid and other quantified components. It was found that the established method was sensitive, precise, and accurate enough for the simultaneous quantification of 18 analytes in PH samples. Significant differences were found among the contents of 18 components in PH samples, no apparent clustering of the quality of PH samples was found to be related to its origins, and the contents of ursolic acid/oleanolic acid were only significantly correlated to the content of sylvestroside I, dipsanoside B, dipsanoside A in PH. Our results suggested that the newly established multi-components quantitative method is an improved approach for quality evaluation of PH samples. Furthermore, the holistic quality was inconsistent among PH samples, and ursolic acid/oleanolic acid alone could not indicate the holistic quality variation trend of PH.PMID:37918282 | DOI:10.1016/j.jpba.2023.115828

Spectrochim Acta A Mol Biomol Spectrosc. 2023 Oct 30;306:123587. doi: 10.1016/j.saa.2023.123587. Online ahead of print.ABSTRACTSurface-enhanced Raman spectroscopy (SERS) has been used in Raman-based metabolomics to provide abundant molecular fingerprint information in situ with extremely high sensitivity, without damaging the sample. However, poor reproducibility, caused by the randomness of the adsorption sites, and the short-range effect of SERS have hindered the development of SERS in metabolomics, resulting in very few SERS reference databases for small-molecule metabolites. In this work, our previously proposed large laser spot-swift mapping SERS method was adopted for the measurement of 24 commercially available metabolite standards, to provide reproducible and reliable references for Raman-based metabolomics study. Among these 24 metabolites, 22 contained no Raman data in PubChem. Other than the SERS spectra data, we extracted and explained the molecular vibration information of these metabolites, and combined with the density functional theory (DFT) calculations, we provided a new possibility for the fast Raman recognition of small-molecule metabolites. Accordingly, a large laser spot-swift mapping SERS database of metabolites in human serum was initially established, which contained not only the original spectral data but also other detailed feature information regarding the Raman peaks. With continuous accumulation, this database could play a promising role in Raman-based metabolomics and other Raman-related research.PMID:37918093 | DOI:10.1016/j.saa.2023.123587