PubMed

Int Microbiol. 2024 Nov 13. doi: 10.1007/s10123-024-00613-8. Online ahead of print.ABSTRACTSocial separation, or the absence of social support, can cause physical and psychological health issues. Social separation is crucial for the welfare of the Yangtze finless porpoise (YFP) in captivity because they face many challenges like frequent social separation, noise from visitors, and animal replacement, which can cause psychological and physiological stress. This research is aimed at assessing the potential negative impacts of social separation on the gut microbiome and metabolome of captive YFP, focusing on the potential imbalances caused by mother-calf separation. The study found that social separation did not alter the alpha and beta diversity of the gut microbes but increased the abundance of disease-associated taxa such as Romboutsia, Terrisporobacter, and Clostridium_sensu_stricto_13 in the MC (mother-calf) group while increasing Paeniclostridium and Clostridium_sensu_stricto_1 associated with host health in the MS (mother-separated) group. The fecal metabolome underwent significant changes during social separation, with stress-associated metabolites like kainic acid, phenethylamine glucuronide, and paxilline upregulated in the MC group and host health-associated metabolites like butyric acid, 6-hydroxyhexanoic acid, and fosinopril downregulated in the MS group. In addition, there was a strong association between the fecal microbiome and the metabolome of captive YFPs. The study enhances our comprehension of the detrimental effects of social separation, which result in disruptions in the gut microbiome and fecal metabolome. The study is aimed at introducing a new method for assessing the health and welfare of endangered mammals in captivity.PMID:39532805 | DOI:10.1007/s10123-024-00613-8

Alcohol Clin Exp Res (Hoboken). 2024 Nov 12. doi: 10.1111/acer.15476. Online ahead of print.ABSTRACTThis critical review summarizes the current state of omics-based biomarkers in the alcohol research field. We first provide definitions and background information on alcohol and alcohol use disorder (AUD), biomarkers, and "omic" technologies. We next summarize using (1) genetic information as risk/prognostic biomarkers for the onset of alcohol-related problems and the progression from regular drinking to problematic drinking (including AUD), (2) epigenetic information as diagnostic biomarkers for AUD and risk biomarkers for alcohol consumption, (3) transcriptomic information as diagnostic biomarkers for AUD, risk biomarkers for alcohol consumption, and (4) metabolomic information as diagnostic biomarkers for AUD, risk biomarkers for alcohol consumption, and predictive biomarkers for response to acamprosate in subjects with AUD. In the final section, the clinical implications of the findings are discussed, and recommendations are made for future research.PMID:39532676 | DOI:10.1111/acer.15476

Life Sci Alliance. 2024 Nov 12;8(1):e202302446. doi: 10.26508/lsa.202302446. Print 2025 Jan.ABSTRACTCell death frequently occurs in the pathogenesis of obesity and metabolic dysfunction-associated fatty liver disease (MAFLD). However, the exact contribution of core cell death machinery to disease manifestations remains ill-defined. Here, we show via the direct comparison of mice genetically deficient in the essential necroptotic regulators, receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL), as well as mice lacking apoptotic caspase-8 in myeloid cells combined with RIPK3 loss, that RIPK3/caspase-8 signaling regulates macrophage inflammatory responses and drives adipose tissue inflammation and MAFLD upon high-fat diet feeding. In contrast, MLKL, divergent to RIPK3, contributes to both obesity and MAFLD in a manner largely independent of inflammation. We also uncover that MLKL regulates the expression of molecules involved in lipid uptake, transport, and metabolism, and congruent with this, we discover a shift in the hepatic lipidome upon MLKL deletion. Collectively, these findings highlight MLKL as an attractive therapeutic target to combat the growing obesity pandemic and metabolic disease.PMID:39532538 | DOI:10.26508/lsa.202302446

Anal Chim Acta. 2024 Dec 1;1331:343314. doi: 10.1016/j.aca.2024.343314. Epub 2024 Oct 9.ABSTRACTBACKGROUND: We introduce TRAM, a triple acquisition strategy on a high-speed quadrupole time-of-flight mass spectrometer for merging non-targeted and targeted metabolomics into one run. TRAM stands for "quasi-simultaneous" acquisition of (1) a full scan MS1, (2) top 30 data-dependent MS2 (DDA), and (3) targeted scheduled MS2 for multiple reaction monitoring (MRM) within measurement cycles of ∼1 s. TRAM combines the selectivity and sensitivity of state-of-the-art targeted MRM-based methods with the full scope of non-targeted analysis enabled by high-resolution mass spectrometry.RESULTS: In this work, we deploy a workflow based on hydrophilic interaction liquid chromatography (HILIC). For a broad panel of metabolites, we provide chromatographic retention times, and optimized conditions as a basis for targeted MRM experiments, listing accurate masses and sum formulas for fragment ions (including fully 13C labeled analogs). Validation experiments showed that TRAM offered (1) linear working ranges and limits of quantification comparable to MRM-only methods, (2) enabled accurate quantification in SRM 1950 human plasma reference material, and (3) was equivalent to DDA-only approaches in non-targeted metabolomics. Metabolomics in human cerebrospinal fluid showcased the power of the strategy, emphasizing the need for high coverage/high throughput metabolomics in clinical studies.SIGNIFICANCE: Acquiring up to 30 data-dependent spectra per MS cycle while still offering gold standard absolute quantification down to low nanomolar concentrations, TRAM allows in-depth profiling and reduces required sample volume, time, cost, and environmental impact.PMID:39532411 | DOI:10.1016/j.aca.2024.343314

Anal Chim Acta. 2024 Dec 1;1331:343313. doi: 10.1016/j.aca.2024.343313. Epub 2024 Oct 9.ABSTRACTBACKGROUND: Estradiol (E2) is a female sex hormone involved in several biological processes. Although E2 levels are commonly measured in blood samples, the use of non-invasive techniques (e.g. determination of salivary E2) would allow for the collection of repeated samples and the inclusion of a greater number of participants. Immunoassay-based techniques to measure salivary E2 failed to accurately mirror the variations observed in the plasmatic concentrations of E2 during the menstrual cycle probably due to the high sensitivity required (in the sub-pg/mL range). Therefore, sensitive and rugged analytical methods for the determination of salivary E2 are required. For this, we developed and validated an analytical methodology for the accurate determination of salivary E2.RESULTS: The method is based on chemical derivatization with 1,2-dimethyl-1H-imidazole-5-sulphonyl chloride and liquid chromatography-tandem mass spectrometry analysis by summing highly-specific SRM transitions. This strategy allowed for increasing the sensitivity of the method. The validation of the method showed an accurate and precise quantification of E2 in 1 mL of saliva even at 250 fg/mL (97 % accuracy and 15 % RSD intra-day, and 104 % accuracy and 18 % RSD inter-day). In order to evaluate its efficacy, we analysed saliva samples from 5 healthy female volunteers collected during a whole menstrual cycle. Our analyses showed that the variations in the concentration of E2 in the measured samples mirrored those expected during a complete menstrual cycle. Additionally, we validated the suitability of our method for determining salivary E2 levels during pregnancy.SIGNIFICANCE: To the best of our knowledge, this is the first method that allows to precisely and accurately measuring E2 in saliva samples along the whole menstrual cycle of healthy females. It is also suitable for the determination of estradiol during pregnancy. Its high sensitivity makes this strategy ideal for the evaluation of the role of hormone production in women's health.PMID:39532410 | DOI:10.1016/j.aca.2024.343313

BMJ Open. 2024 Nov 12;14(11):e091567. doi: 10.1136/bmjopen-2024-091567.ABSTRACTBACKGROUND: Acute pulmonary embolism (PE) mortality is linked to abrupt rises in pulmonary artery (PA) pressure due to mechanical obstruction and pulmonary vasoconstriction, leading to right ventricular (RV) dilation, increased RV wall tension and oxygen demand, but compromised right coronary artery oxygen supply. Oxygen is a known pulmonary vasodilator, and in preclinical animal models of PE, supplemental oxygen reduces PA pressures and improves RV function. However, the mechanisms driving these interactions, especially in humans, remain poorly understood. The overall objective of the supplemental oxygen in pulmonary embolism (SO-PE) study is to investigate the mechanisms of supplemental oxygen in patients with acute PE.METHODS AND ANALYSIS: This randomised, double-blind, cross-over trial at Massachusetts General Hospital will include adult patients with acute PE and evidence of RV dysfunction but without hypoxaemia (SaO2 ≥90% on room air). We will enrol 80 patients, each serving as their own control, with 40 randomised to start on supplemental oxygen, and 40 randomised to start on room air. Over 180 min, patients will alternate between supplemental oxygen delivered by non-rebreather mask (60% FiO2) and room air (21% FiO2). The primary outcome will be the difference in pulmonary artery systolic pressure with and without oxygen. Secondary outcomes include additional echocardiographic measures, metabolomic profiles, vital signs and dyspnoea scores. Echocardiographic data will be compared by a paired t-test or Wilcoxon signed-rank test. For metabolomic analyses, we will perform multivariable mixed effects logistic regression models and calculate false discovery rate (q-value ≤0.05) to account for multiple comparisons. Data will be collected in compliance with National Institutes of Health and National Heart Lung and Blood Institute (NHLBI) policies for data and safety monitoring.ETHICS AND DISSEMINATION: The SO-PE study is funded by the NHLBI and has been approved by the Institutional Review Board of Mass General Brigham (no. 2023P000252). The study will comply with the Helsinki Declaration on medical research involving human subjects. All participants will provide prospective, written informed consent.TRIAL REGISTRATION NUMBER: NCT05891886.PMID:39532350 | DOI:10.1136/bmjopen-2024-091567

Nutr Res. 2024 Sep 28;132:95-111. doi: 10.1016/j.nutres.2024.09.018. Online ahead of print.ABSTRACTOxidative and nitrosative stress play pivotal roles in normal physiological processes and the pathogenesis of metabolic disorders. Previous studies from our lab demonstrated insulin resistance (IR), and dyslipidemia in iNOS-/- mice, emphasizing the importance of maintaining optimal redox balance. These mice exhibited altered gut microbiota with decreased Lactobacillus. Therefore, we hypothesized that Lactobacillus supplementation could mitigate metabolic disturbances in iNOS-/- mice. To test this hypothesis, iNOS-/- mice and wild-type (WT) mice were divided into four groups: iNOS-/- with or without Lactobacillus supplementation, WT with or without Lactobacillus supplementation and glucose tolerance, insulin resistance, gluconeogenesis, lipids, gene expression related to glucose and lipid metabolism (qPCR), fecal gut microbiota (16S rRNA sequencing), and serum and caecum metabolomics (LC-MS) were monitored. IR and dyslipidemic iNOS-/- mice exhibited reduced microbial diversity, diminished presence of Lactobacillus, and altered serum metabolites, indicating metabolic dysregulation. Lactobacillus supplementation in iNOS-/- mice effectively reversed glucose intolerance, IR, dyslipidemia, and associated metabolic irregularities compared to WT. These improvements correlated with changes in gene expression related to fatty acid synthesis in liver and adipose tissue, lipid oxidation in liver, and lipid efflux in intestinal tissue as compared to untreated iNOS-/- mice. Despite the positive effects on metabolic markers, Lactobacillus supplementation did not reduce body weight or rectify disrupted energy balance, as evidenced by reduced VCO2 production, heat generation, and metabolic rates in iNOS-/- mice. The results suggest that Lactobacillus supplementation ameliorates metabolic disturbances but did not fully restore disrupted energy balance, highlighting complex interactions between the gut microbiome and metabolism.PMID:39532058 | DOI:10.1016/j.nutres.2024.09.018

Food Chem. 2024 Nov 7;465(Pt 1):141900. doi: 10.1016/j.foodchem.2024.141900. Online ahead of print.ABSTRACTGarcinia subfalcata, an edible species endemic to China, has limited research on its chemical composition and biological effects. This study aimed to analyze metabolites in different plant parts and identify potential anticancer constituents. Using UPLC-IMS-QTOF-MS-based metabolomics, a total of 124 compounds were identified, with xanthones, flavonoids and phloroglucinols being the predominant compounds. PCA and PLS-DA analyses revealed significant metabolite differences among plant parts, identifying 28 differential metabolites, including bronianone and (±)-fukugiside. Antiproliferative assays showed varying bioactivities, with bark exhibiting the highest cytotoxicity against A549, HeLa and HGC-27 cells (IC50: 2.72-5.71 μg/mL). Mechanism studies indicated that the bark inhibited cell proliferation by inducing apoptosis and disrupting mitochondrial membrane potential. S-plot models revealed 23 potential anticancer constituents, including (-)-epicatechin and 1,7-dihydroxyxanthone. These findings highlight G. subfalcata's potential as a source of functional food supplements and medicinal agents and indicate the efficacy of UPLC-IMS-QTOF-MS-based metabolomics in exploring bioactive components within Garcinia.PMID:39531968 | DOI:10.1016/j.foodchem.2024.141900

Food Chem. 2024 Nov 8;465(Pt 1):141954. doi: 10.1016/j.foodchem.2024.141954. Online ahead of print.ABSTRACTHigh Voltage Alternating Electric Field (HVAEF), as an emerging postharvest preservation technology, is environmentally friendly and has garnered significant attention from scholars. This study investigated the effects of HVAEF on the postharvest quality and metabolite changes in 'Shine Muscat' grapes stored at near-freezing temperatures. The results demonstrated that HVAEF halved the weight loss and decay rate, inhibited browning by preserving polyphenol content, and reduced polyphenol oxidase and peroxidase activities, thereby extending the storage time by more than 20 days. Metabolomic analysis of the grape berries from the upper, middle, and bottom parts of the bunch revealed that the upper berries contained higher sugar levels and were more significantly influenced by HVAEF treatment. Additionally, HVAEF notably reduced the accumulation of amino acids, such as valine, leucine, and lysine, compared to the control. This study provides new insights into the enhancement of quality in fresh fruits and vegetables through HVAEF technology.PMID:39531963 | DOI:10.1016/j.foodchem.2024.141954

Phytomedicine. 2024 Nov 3;135:156201. doi: 10.1016/j.phymed.2024.156201. Online ahead of print.ABSTRACTINTRODUCTION: Pidanjiangtang (PDJT) is a traditional Chinese medicine formula empirically used to treat impaired glucose tolerance (IGT) based on the "Pidan" theory from the classic ancient book Nei Jing. However, the mechanism of PDJT intervention for IGT remains to be studied.OBJECTIVE: This study aims to explore the mechanism of PDJT granules intervention in IGT by integrating gut microbiome and UHPLC-MS untargeted metabolomics.MATERIALS AND METHODS: The IGT model was established in 6-week-old male Sprague-Dawley (SD) rats by feeding them a high-fat diet and using an STZ injection. The low, medium, and high doses of PDJT were used for six weeks. metformin (Glucophage) was used as the positive control drug. The efficacy of PDJT was evaluated using fasting blood glucose (FBG), blood glucose maximum (BGmax), blood lipid, and inflammatory factor levels. Finally, 16S rDNA gut microbiome sequencing with metabolomics analysis was used to explore the pharmacological mechanism of PDJT intervention in IGT.RESULTS: PDJT could reverse the phenotype of IGT rats, reduce blood glucose levels, improve lipid metabolism disorder, and reduce inflammatory response. Gut microbiome analysis found that PDJT can improve gut microbiota composition and abundance of three phyla (Firmicutes, Bacteroidota, Desulfobacterota) and four genera (unclassified_f__Lachnospiraceae, Ruminococcus, Allobaculum, Desulfovibrio), which play an important role in the process of PDJT intervention on glucose metabolism and lipid metabolism in IGT rats. UHPLC-MS untargeted metabolomics showed that PDJT could regulate the levels of 258 metabolites in lipid metabolism pathways, inflammatory response pathways, fat and protein digestion, and absorption. The combined analysis of the two omics showed that improving the body's metabolism by gut microbes may be the possible mechanism of PDJT in treating IGT. Thus, this study provides a new method to integrate gut microbiome and UHPLC-MS untargeted metabolomics to evaluate the pharmacodynamics and mechanism of PDJT intervention in IGT, providing valuable ideas and insights for future research on the treatment of IGT with traditional Chinese medicine.PMID:39531936 | DOI:10.1016/j.phymed.2024.156201

Enzyme Microb Technol. 2024 Nov 9;182:110546. doi: 10.1016/j.enzmictec.2024.110546. Online ahead of print.ABSTRACTMicroalgae-based biofuel production is cost-effective only in a biorefinery, where valuable co-products offset high costs. Fatty acids produced by photosynthetic microalgae can serve as raw materials for bioenergy and pharmaceuticals. This study aims to understand the metabolic imprints of Scenedesmus sp. CABeR52, to decipher the physiological mechanisms behind lipid accumulation under nitrogen deprivation. Metabolomics profiles were generated using gas chromatography-mass spectrometry (GC-MS) of Scenedesmus sp. CABeR52 subjected to nutrient deprivation. Our initial data sets indicate that deprived cells have an increased accumulation of lipids (278.31 mg.g-1 dcw), 2.0 times higher than the control. The metabolomic profiling unveils a metabolic reprogramming, highlighting the upregulation of key metabolites involved in fatty acid biosynthesis, such as citric acid, succinic acid, and 2-ketoglutaric acid. The accumulation of trehalose, a stress-responsive metabolite, further underscores the microalga's adaptability. Interestingly, we found that a new fatty acid, nervonic acid, was identified in the complex, which has a significant role in brain development. These findings provide valuable insights into the metabolic pathways governing lipid accumulation in Scenedesmus sp., paving the way for its exploitation as a sustainable biofuel feedstock.PMID:39531895 | DOI:10.1016/j.enzmictec.2024.110546

Poult Sci. 2024 Nov 3;103(12):104495. doi: 10.1016/j.psj.2024.104495. Online ahead of print.ABSTRACTTo deeply understanding the impact of peripheral energy level on the development of ovaries during the sexual maturation of chicken, in this study, the ovaries and serum of sexually mature and immature chickens at the same age from different energy level groups were collected, and the proteome and metabolome were detected. The results of ovarian and serum metabolomics revealed that dietary energy levels affected the energy metabolism and fatty acid oxidation of ovary in chicken, including the up-regulated expression of dihydroacetone phosphate and α-linolenic acid in high energy level groups. The results of proteomics showed that peripheral energy levels affected the catecholamine biosynthesis and metabolism in ovary before sexual maturation. The integrating analysis revealed that increased energy flux may influence ovarian development by regulating cholesterol reserves and steroid hormone synthesis in the ovaries. In vitro, the cultivation of chicken primary granulosa cells showed that sterol carrier protein 2 played a role in fatty acid synthesis and metabolism but did not significantly affect progesterone synthesis. Overall, dietary energy levels may be involved in the development of the ovaries during sexual maturation by influencing energy metabolism, biosynthesis of unsaturated fatty acids and steroid hormone within the ovaries.PMID:39531803 | DOI:10.1016/j.psj.2024.104495

PLoS Biol. 2024 Nov 12;22(11):e3002875. doi: 10.1371/journal.pbio.3002875. eCollection 2024 Nov.ABSTRACTRising sea surface temperatures are increasingly causing breakdown in the nutritional relationship between corals and algal endosymbionts (Symbiodiniaceae), threatening the basis of coral reef ecosystems and highlighting the critical role of coral reproduction in reef maintenance. The effects of thermal stress on metabolic exchange (i.e., transfer of fixed carbon photosynthates from symbiont to host) during sensitive early life stages, however, remains understudied. We exposed symbiotic Montipora capitata coral larvae in Hawai'i to high temperature (+2.5°C for 3 days), assessed rates of photosynthesis and respiration, and used stable isotope tracing (4 mM 13C sodium bicarbonate; 4.5 h) to quantify metabolite exchange. While larvae did not show any signs of bleaching and did not experience declines in survival and settlement, metabolic depression was significant under high temperature, indicated by a 19% reduction in respiration rates, but with no change in photosynthesis. Larvae exposed to high temperature showed evidence for maintained translocation of a major photosynthate, glucose, from the symbiont, but there was reduced metabolism of glucose through central carbon metabolism (i.e., glycolysis). The larval host invested in nitrogen cycling by increasing ammonium assimilation, urea metabolism, and sequestration of nitrogen into dipeptides, a mechanism that may support the maintenance of glucose translocation under thermal stress. Host nitrogen assimilation via dipeptide synthesis appears to be used for nitrogen limitation to the Symbiodiniaceae, and we hypothesize that nitrogen limitation contributes to retention of fixed carbon by favoring photosynthate translocation to the host. Collectively, our findings indicate that although these larvae are susceptible to metabolic stress under high temperature, diverting energy to nitrogen assimilation to maintain symbiont population density, photosynthesis, and carbon translocation may allow larvae to avoid bleaching and highlights potential life stage specific metabolic responses to stress.PMID:39531470 | DOI:10.1371/journal.pbio.3002875

Kidney360. 2024 Nov 12. doi: 10.34067/KID.0000000630. Online ahead of print.ABSTRACTBACKGROUND: In acute kidney injury, macrophages play a major role in regulating inflammation. Classically activated macrophages (M1) undergo drastic metabolic reprogramming during their differentiation and upregulate the aerobic glycolysis pathway to fulfill their pro-inflammatory functions. NAD+ regeneration is crucial for the maintenance of glycolysis and the most direct pathway by which this occurs is via the fermentation of pyruvate to lactate, catalyzed by lactate dehydrogenase A (LDHA). Our previous study determined that LDHA is predominantly expressed in the proximal segments of the nephron in the mouse kidney and increases with hypoxia. This study investigates the potential of LDHA as a therapeutic target for inflammation by exploring its role in macrophage function in vitro.METHODS: Bone-marrow-derived macrophages (BMDMs) were isolated from myeloid-specific LDHA knockout mice derived from crossbreeding LysM-Cre transgenic mice and LDHA floxed mice. RNA sequencing and LC-MS/MS metabolomics analyses were used in this study to determine the effect of LDHA deletion on BMDM following stimulation with IFN-γ.RESULTS: LDHA deletion in IFN-γ BMDMs resulted in a significant alteration of the macrophage activation and functional pathways, and change in glycolytic, cytokine, and chemokine gene expression. Metabolite concentrations associated with pro-inflammatory macrophage profiles were diminished while anti-inflammatory-associated ones were increased in LDHA KO BMDMs. Glutamate and amino sugars metabolic pathways were significantly affected by the LDHA deletion. A combined muti-omics analysis highlighted changes in Rap1 signaling, cytokine-cytokine receptor interaction, focal adhesion, and MAPK signaling metabolism pathways.CONCLUSIONS: Deletion of LDHA in macrophages results in a notable reduction in the pro-inflammatory profile and concurrent upregulation of anti-inflammatory pathways. These findings suggest that LDHA could serve as a promising therapeutic target for inflammation, a key contributor to the pathogenesis of acute kidney injury.PMID:39531318 | DOI:10.34067/KID.0000000630

Anal Chem. 2024 Nov 12. doi: 10.1021/acs.analchem.4c04400. Online ahead of print.ABSTRACTVarious polarity chemicals exist in complex samples, such as plasma; nontargeted comprehensive analysis naturally requires multiple polar-extracted solvents; consequently, the polarity of the solvent plays a crucial role in the extraction efficiency of analytes from complex samples. In the present study, based on the diffusion behavior and nanoconfinement effect of solvents in the nanoconfined space, the polarity gradient solvent confinement liquid-phase nanoextraction (PGSC-NLPNE) protocol aimed to perform a one-step nontargeted analysis of a wide range of metabolites in plasma was established. The continuously wide range of extracted solvent polarities on carbon nanofibers/carbon fiber (CNFs/CF) membranes was achieved using a mixture of hexane, dichloromethane, methanol, and water as nanoconfined solvents. The polarities (Log P) of gradient solvents ranged from -1.38 to 3.94. Correlational analyses indicated that metabolites with Log P values ranging from -1.90 to 3.84 were closely related according to similarity-intermiscibility theory. Coupled with a homemade modified guard column device, CNFs/CF membrane cartridge (CCMC), a PGSC-NLPNE-UHPLC-MS online protocol was established and applied in plasma untargeted analysis. By comparing metabolome coverage, reproducibility, and extraction recovery with protein precipitation and two-step liquid-liquid extraction commonly used in untargeted analysis, the PGSC-NLPNE-CCMC protocol demonstrated higher reproducibility and recovery. This protocol has shown great potential for ultrafast analysis of plasma untargeted metabolomics with broader metabolome coverage. It could be a potential tool to rapidly screen out valuable biomarkers related to diseases in the clinic.PMID:39531215 | DOI:10.1021/acs.analchem.4c04400

Inflammation. 2024 Nov 12. doi: 10.1007/s10753-024-02184-2. Online ahead of print.ABSTRACTChanges in gut flora are associated with liver fibrosis. The interactions of host with intestinal flora are still unknown, with little research investigating such interactions with comprehensive multi-omics data. The present work analyzed and integrated large-scale multi-omics transcriptomics, microbiome, metabolome, and single-cell RNA-sequencing datasets from Kaempferol-treated and untreated control groups by advanced bioinformatics methods. This study concludes that kaempferol dose-dependently improved serum markers (like AST, ALT, TBil, Alb, and PT) and suppressed fibrosis markers (including HA, PC III, LN, α-SMA, and Collagen I), while kaempferol also increased body weight. Mechanistically, kaempferol improved the metabolic levels of intestinal flora dysbiosis and associated lipids. This was achieved by increasing the abundance of g__Robinsoniella, g__Erysipelotrichaceae_UCG-003, g__Coriobacteriaceae_UCG-002, and 5-Methylcytidine, all-trans-5,6- Epoxyretinoic acid, LPI (18:0), LPI (20:4), etc. to achieve this. Kaemferol exerts anti-inflammatory and immune-enhancing effects by down-regulating the Th17/IL-17 signaling pathway in PDGF-induced LX2 cells. In addition, kaempferol administration remarkably elevated CD4 + T and CD8 + T cellular proportions, thereby activating immune cells for protecting the body and controlling inflammatory conditions. The combined interaction of multiple data may explain how Kaempferol modulates the intestinal flora thereby remodeling the hepatocyte population and alleviating liver fibrosis.PMID:39531210 | DOI:10.1007/s10753-024-02184-2

Appl Microbiol Biotechnol. 2024 Nov 12;108(1):512. doi: 10.1007/s00253-024-13341-w.ABSTRACTSalmonella, a common pathogenic bacterium in food, can have a severe impact on food safety and consumer health. At present, Salmonella infection is controlled primarily by the use of antibiotics, which creates unsafe factors for food safety. Thus, finding a natural antibacterial agent is highly practical. In this study, resveratrol was screened from 17 kinds of polyphenols, and its inhibitory mechanism and effects on metabolites of Salmonella typhimurium were investigated to occur through cell wall and membrane damage and metabolomics analysis. The results revealed that the minimum inhibitory concentration of resveratrol against S. typhimurium was 250 μg/mL. After treatment with resveratrol, the lag period of the strain was prolonged, and the cell wall and membrane structure were destroyed. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) further confirmed that resveratrol induced damage to the cell walls and cell membrane. The metabolic profile of S. typhimurium following resveratrol treatment was analysed by gas chromatography‒mass spectrometry. In the metabolome evaluation, we screened 23 differentially abundant metabolites, including 11 upregulated and 12 downregulated metabolites. Eight metabolic pathways of S. typhimurium, including pathways important for amino acid metabolism and the tricarboxylic acid (TCA) cycle, exhibited significant changes after resveratrol treatment. The verification results of the citric acid content, cis-aconitase activity, and ATP content further revealed that the tricarboxylic acid cycle and other related metabolic pathways of S. typhimurium were affected. These results could provide a theoretical possibility for the use of resveratrol as a plant-derived bacteriostatic for food safety problems caused by S. typhimurium. KEY POINTS: • The mechanism of bacteriostasis was studied via metabolomics • Resveratrol causes the death of Salmonella by disrupting the cell wall and membrane.PMID:39531061 | DOI:10.1007/s00253-024-13341-w

Physiol Res. 2024 Nov 12;73(5):687-702.ABSTRACTOver recent decades, advancements in omics technologies, such as proteomics, genomics, epigenomics, metabolomics, transcriptomics, and microbiomics, have significantly enhanced our understanding of the molecular mechanisms underlying various physiological and pathological processes. Nonetheless, the analysis and interpretation of vast omics data concerning reproductive diseases are complicated by the cyclic regulation of hormones and multiple other factors, which, in conjunction with a genetic makeup of an individual, lead to diverse biological responses. Reproductomics investigates the interplay between a hormonal regulation of an individual, environmental factors, genetic predisposition (DNA composition and epigenome), health effects, and resulting biological outcomes. It is a rapidly emerging field that utilizes computational tools to analyze and interpret reproductive data, with the aim of improving reproductive health outcomes. It is time to explore the applications of reproductomics in understanding the molecular mechanisms underlying infertility, identification of potential biomarkers for diagnosis and treatment, and in improving assisted reproductive technologies (ARTs). Reproductomics tools include machine learning algorithms for predicting fertility outcomes, gene editing technologies for correcting genetic abnormalities, and single cell sequencing techniques for analyzing gene expression patterns at the individual cell level. However, there are several challenges, limitations and ethical issues involved with the use of reproductomics, such as the applications of gene editing technologies and their potential impact on future generations are discussed. The review comprehensively covers the applications and advancements of reproductomics, highlighting its potential to improve reproductive health outcomes and deepen our understanding of reproductive molecular mechanisms.PMID:39530905

Food Funct. 2024 Nov 12. doi: 10.1039/d4fo90094d. Online ahead of print.ABSTRACTCorrection for 'Using integrated transcriptomics and metabolomics to explore the effects of infant formula on the growth and development of small intestinal organoids' by Xianli Wang et al., Food Funct., 2024, 15, 9191-9209, https://doi.org/10.1039/d4fo01723d.PMID:39530838 | DOI:10.1039/d4fo90094d

J Exp Bot. 2024 Nov 12:erae457. doi: 10.1093/jxb/erae457. Online ahead of print.ABSTRACTPriming modulates plant stress responses before the stress appears, increasing the ability of the primed plant to endure adverse conditions and thrive. In this context, we investigated the effect of biological (i.e., arbuscular mycorrhizal fungi, AMF) agents and natural compounds (i.e., salicylic acid applied alone or combined with chitosan) against water deficit and salinity on a commercial tomato genotype (cv. Moneymaker). Effects of seed treatments on AMF colonization were evaluated, demonstrating the possibility of using them in combination. Responses to water and salt stresses were analysed on primed plants alone or in combination with the AMF inoculum in soil. Trials were conducted on potted plants by subjecting them to water deficit or salt stress. The effectiveness of chemical seed treatments, both alone and in combination with post-germination AM fungal inoculation, was investigated using a multidisciplinary approach that included eco-physiology, biochemistry, transcriptomics, and untargeted metabolomics. Results showed that chemical seed treatment and AM symbiosis modified the tomato response to water deficit and salinity triggering a remodelling of both transcriptome and metabolome, which ultimately elicited the plant antioxidant and osmoprotective machinery. The plant physiological adaptation to both stress conditions improved, confirming the success of the adopted approaches in enhancing stress tolerance.PMID:39530649 | DOI:10.1093/jxb/erae457