PubMed

Plant Physiol Biochem. 2024 May 30;212:108785. doi: 10.1016/j.plaphy.2024.108785. Online ahead of print.ABSTRACTHigh concentrations of copper can pollute coastal waters, primarily from agricultural runoff and mining activities, which can harm marine organisms, including seagrasses. The molecular mechanism of copper toxicity to seagrass currently remains unclear. To determine the response to copper, physiological and multi-omic analyses were conducted to explore the molecular mechanism by which copper affects the global threatened seagrass Halophila beccarii Asch. Excessive copper stress causes oxidative damage and stimulates the activity of the antioxidant enzyme system to remove excess reactive oxygen species (ROS), thereby reducing the damage caused by copper stress. Cu increases the activities of superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), peroxidase (EC 1.11.1.7), ascorbate peroxidase (EC 1.11.1.11), glutathione peroxidase (EC 1.11.1.9), ascorbate oxidase (EC 1.10.3.3), glutathione reductase (EC 1.6.4.2), and dehydroascorbate reductase (EC 1.8.5.1) and the content of malondialdehyde and reduces the activity of monodehydroascorbate reductase (EC 1.6.5.4). Under copper stress, H. beccarii upregulates the metabolic pathways of steroid biosynthesis and cutin, suberin, and wax biosynthesis, downregulates the metabolic pathways of arginine and proline metabolism and fructose and mannose metabolism; the levels of expression of the ribosome-related genes; upregulates the levels of expression of circadian rhythm-related proteins and downregulates the levels of glutathione metabolism and the proteins related to carbon fixation. This study provides new insights into the response of seagrass to copper stress and reports potential candidate metabolites, genes, and proteins that can be considered as biomarkers to improve the protection and management of seagrass meadows.PMID:38824692 | DOI:10.1016/j.plaphy.2024.108785

Nat Prod Res. 2024 Jun 2:1-7. doi: 10.1080/14786419.2024.2356714. Online ahead of print.ABSTRACTThyme is a commercial spice widely used in food, cosmetics, and pharmaceutical industries. Three popular genera in food and traditional medicine, including Zataria Boiss., Thymus L., and Ziziphora L., are considered as thyme-like plants in Iran. Thyme has been standardised based on phenolic monoterpenes, which are abundant in the essential oils of these three genera. Apart from monoterpenes, the flavonoid naringenin, the triterpene oleanolic acid, and phytosterols such as β-sitosterol were abundant in Zataria, Thymus, and Ziziphora samples, respectively. Therefore, employing current analytical techniques on the basis of thymol and carvacrol may be insufficient to differentiate Thymus spp from similar medicinal plants including Zataria and Ziziphora spp. In this study, we applied NMR-based metabolomics using multivariate analyses to develop quality control of thyme and their similar products. Our findings revealed that NMR-based metabolomics can be a useful approach in differentiating Zataria, Thymus, and Ziziphora.PMID:38824635 | DOI:10.1080/14786419.2024.2356714

BMC Genomics. 2024 Jun 1;25(1):547. doi: 10.1186/s12864-024-10483-z.ABSTRACTBACKGROUND: Environmental temperature is critical in regulating biological functions in fish. S. prenanti is a kind of cold-water fish, but of which we have little knowledge about the metabolic adaptation and physiological responses to long-term cold acclimation.RESULTS: In this study, we determined the physiological responses of S. prenanti serum after 30 days of exposure to 6℃. Compared with the control group, the levels of TC, TG, and LDL-C in the serum were significantly (P < 0.05) increased, and the level of glucose was significantly (P < 0.05) decreased under cold acclimation. Cold acclimation had no effect on the gene expression of pro-inflammatory factors and anti-inflammatory factors of S. prenanti. Metabolomics analysis by LC-MS showed that a total of 60 differential expressed metabolites were identified after cold acclimation, which involved in biosynthesis of amino acids, biosynthesis of unsaturated fatty acids, steroid degradation, purine metabolism, and citrate cycle pathways.CONCLUSION: The results indicate that cold acclimation can alter serum metabolites and metabolic pathways to alter energy metabolism and provide insights for the physiological regulation of cold-water fish in response to cold acclimation.PMID:38824590 | DOI:10.1186/s12864-024-10483-z

BMC Genomics. 2024 Jun 1;25(1):551. doi: 10.1186/s12864-024-10452-6.ABSTRACTBecause number of matured muscle fibers in poultry does not increase after birth, the meat yield is mainly determined during embryogenesis. We previously indicated breast muscle grew rapidly from 18th day after hatching (E18) to E27, and almost stopped from E27 to E34 of Jiaji ducks, while the mechanism is unclear. This study utilized RNA-seq to explore the related genes of muscle development and their relationship with small molecule metabolites at E18, E27 and E34 of Jiaji ducks. Several thousand differentially expressed genes (DEGs) were detected among E18, E27 and E34. DEGs expression profiles included 8 trend maps, among which trend 1 was opposite to and trend 6 was consistent with breast muscle development trend of Jiaji ducks. Through joint analysis between trend 1 of DEGs and trend 1 of differential metabolites (DEMs), protein digestion and absorption pathway stood out. The decrease of COL8A2 gene expression will lead to the decrease of arginine content, which will inhibit the development of breast muscle in embryonic Jiaji duck. Similarly, joint analysis between trend 6 of DEGs and trend 6 of DEMs indicated the increase of GAMT gene expression will cause the increase of proline content, and then promote the development of breast muscle of Jiaji duck in embryonic period. These results will be helpful for further understanding the mechanism of muscle yields of Jiaji ducks.PMID:38824564 | DOI:10.1186/s12864-024-10452-6

Cell Biosci. 2024 Jun 1;14(1):69. doi: 10.1186/s13578-024-01248-y.ABSTRACTHepatocellular carcinoma (HCC) incidence is continuously increasing worldwide, due to the rise of metabolic dysfunction-associated steatohepatitis (MASH) cases. Cholesterol is an essential driver of the metabolic dysregulations that promote HCC progression. Liver X Receptor (LXR) is a nuclear receptor best known for the regulation of lipid and cholesterol homeostasis, with a prominent function in the liver and in the intestine. Here, we aimed to explore whether modifications in intestinal lipid metabolism may contribute to the onset of HCC, particularly taking into account cholesterol metabolism and LXRs. To study the progression of MASH to HCC, we induced metabolic HCC in wild-type male mice and mice carrying an intestinal chronic activation of LXRα. Also, we analysed human hepatic transcriptome datasets. The increased consumption of fat and carbohydrates drives the intestinal activation of LXRα and accelerates the onset of the hepatic tumours. Chronic intestinal-specific activation of LXRα enhances HCC progression only in the presence of a high cholesterol intake. In HCC, despite the increased hepatic cholesterol content, LXR is not active, thus driving liver cancer development. Intriguingly, in line with these results in the mouse model, LXR transcriptome is also downregulated in human hepatocarcinoma and its expression level in liver tumours directly correlates with a decreased survival rate in patients. Overall, our findings establish the relevance of the intestine in influencing the susceptibility to MASH-HCC and point to intestinal LXRα activation as a driver of metabolic liver cancer in the presence of dietary cholesterol.PMID:38824560 | DOI:10.1186/s13578-024-01248-y

J Transl Med. 2024 Jun 1;22(1):528. doi: 10.1186/s12967-024-05350-0.ABSTRACTGiven the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 μmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.PMID:38824544 | DOI:10.1186/s12967-024-05350-0

Sci Rep. 2024 Jun 1;14(1):12598. doi: 10.1038/s41598-024-63280-9.ABSTRACTTo tackle the difficulty of extracting features from one-dimensional spectral signals using traditional spectral analysis, a metabolomics analysis method is proposed to locate two-dimensional correlated spectral feature bands and combine it with deep learning classification for wine origin traceability. Metabolomics analysis was performed on 180 wine samples from 6 different wine regions using UPLC-Q-TOF-MS. Indole, Sulfacetamide, and caffeine were selected as the main differential components. By analyzing the molecular structure of these components and referring to the main functional groups on the infrared spectrum, characteristic band regions with wavelengths in the range of 1000-1400 nm and 1500-1800 nm were selected. Draw two-dimensional correlation spectra (2D-COS) separately, generate synchronous correlation spectra and asynchronous correlation spectra, establish convolutional neural network (CNN) classification models, and achieve the purpose of wine origin traceability. The experimental results demonstrate that combining two segments of two-dimensional characteristic spectra determined by metabolomics screening with convolutional neural networks yields optimal classification results. This validates the effectiveness of using metabolomics screening to determine spectral feature regions in tracing wine origin. This approach effectively removes irrelevant variables while retaining crucial chemical information, enhancing spectral resolution. This integrated approach strengthens the classification model's understanding of samples, significantly increasing accuracy.PMID:38824219 | DOI:10.1038/s41598-024-63280-9

Cell Death Dis. 2024 Jun 1;15(6):387. doi: 10.1038/s41419-024-06774-8.ABSTRACTObesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms have not been sufficiently elucidated. Mitochondria modulate the viability, plasticity, proliferative capacity, and differentiation potential of MSCs. We hypothesized that alterations in the 5-hydroxymethylcytosine (5hmC) profile of mitochondria-related genes may mediate obesity-driven dysfunction of human adipose-derived MSCs. MSCs were harvested from abdominal subcutaneous fat of obese and age/sex-matched non-obese subjects (n = 5 each). The 5hmC profile and expression of nuclear-encoded mitochondrial genes were examined by hydroxymethylated DNA immunoprecipitation sequencing (h MeDIP-seq) and mRNA-seq, respectively. MSC mitochondrial structure (electron microscopy) and function, metabolomics, proliferation, and neurogenic differentiation were evaluated in vitro, before and after epigenetic modulation. hMeDIP-seq identified 99 peaks of hyper-hydroxymethylation and 150 peaks of hypo-hydroxymethylation in nuclear-encoded mitochondrial genes from Obese- versus Non-obese-MSCs. Integrated hMeDIP-seq/mRNA-seq analysis identified a select group of overlapping (altered levels of both 5hmC and mRNA) nuclear-encoded mitochondrial genes involved in ATP production, redox activity, cell proliferation, migration, fatty acid metabolism, and neuronal development. Furthermore, Obese-MSCs exhibited decreased mitochondrial matrix density, membrane potential, and levels of fatty acid metabolites, increased superoxide production, and impaired neuronal differentiation, which improved with epigenetic modulation. Obesity elicits epigenetic changes in mitochondria-related genes in human adipose-derived MSCs, accompanied by structural and functional changes in their mitochondria and impaired fatty acid metabolism and neurogenic differentiation capacity. These observations may assist in developing novel therapies to preserve the potential of MSCs for tissue repair and regeneration in obese individuals.PMID:38824145 | DOI:10.1038/s41419-024-06774-8

Food Res Int. 2024 Jul;188:114476. doi: 10.1016/j.foodres.2024.114476. Epub 2024 May 9.ABSTRACTKimchi cabbage, the key ingredient in kimchi, is cultivated year-round to meet high production demands. This study aimed to examine the effects of seasonal harvesting (spring, summer, fall, and winter) on the microbial and metabolic profiles of kimchi during 30 days of fermentation. Lactic acid bacteria distribution is notably influenced by seasonal variations, with Latilactobacillus dominant in fall-harvested kimchi group and Weissella prevailing in spring, summer, and winter. The microbial communities of spring and fall group exhibited similar profiles before fermentation, whereas the microbial communities and metabolic profiles of spring and summer group were similar after 30 days of fermentation. Seasonal disparities in metabolite concentrations, including glutamic acid, serine, and cytosine, persist throughout fermentation. This study provides a comprehensive understanding of the substantial impact of seasonal harvesting of kimchi cabbage on the microbial and metabolic characteristics of kimchi, providing valuable insights into producing kimchi with diverse qualities.PMID:38823866 | DOI:10.1016/j.foodres.2024.114476

Food Res Int. 2024 Jul;188:114439. doi: 10.1016/j.foodres.2024.114439. Epub 2024 May 6.ABSTRACTTropane alkaloids (TAs) are secondary metabolites from weeds that can contaminate cereals and vegetables during harvest. Due to their toxicity, the Regulation (EC) 2023/915 sets maximum levels for atropine and scopolamine in cereal-based foods for infants containing millet, sorghum, buckwheat or their derived products. The aim of this study was to evaluate the effect of pH and temperature on the stability of TAs, as possible parameters in thermal processing to mitigate this chemical hazard in cereal-based infant food. The effect of pH (4 and 7) and temperature (80 °C and 100 °C) was assessed in buffer solutions. Also, treatment at 180 °C was performed in spiked and naturally incurred millet flour to assess the effect of high temperature, simulating cooking or drying, on the stability of TAs in the cereal matrix. The fate of 24 TAs was assessed by UHPLC-MS/MS. TAs showed high thermostability, although it was variable depending on the specific compound, pH, temperature and treatment time. In buffer solutions, higher degradation was found at 100 °C and pH 7. In spiked millet flour at 180 °C for 10 min, scopolamine and atropine contents decreased by 25 % and 22 %, similarly to other TAs which also showed a slow thermal degradation. Atropine, scopolamine, anisodamine, norscopolamine, scopine and scopoline were found in naturally contaminated millet flour. Interestingly, naturally incurred atropine was more thermostable than when spiked, showing a protective effect of the cereal matrix on TAs degradation. The present results highlight the need for an accurate monitorization of TAs in raw materials, as this chemical hazard may remain in infant cereal-based food even after intense thermal processing.PMID:38823829 | DOI:10.1016/j.foodres.2024.114439

Food Res Int. 2024 Jul;188:114309. doi: 10.1016/j.foodres.2024.114309. Epub 2024 Apr 25.ABSTRACTPrevious studies have demonstrated that Ligilactobacillus salivarius CCFM 1266 exhibits anti-inflammatory properties and the capability to synthesize niacin. This study aimed to investigate the fermentative abilities of L. salivarius CCFM 1266 in fermented milk. Metabonomic analysis revealed that fermentation by L. salivarius CCFM 1266 altered volatile flavor compounds and metabolite profiles, including heptanal, nonanal, and increased niacin production. Genomic investigations confirmed that L. salivarius CCFM 1266 possess essential genes for the metabolism of fructose and mannose, affirming its proficiency in utilizing fructooligosaccharides and mannan oligosaccharides. The addition of fructooligosaccharides and mannan oligosaccharides during the fermentation process significantly facilitated the proliferation of L. salivarius CCFM 1266 in fermented milk, with growth exceeding 107 colony-forming units (CFU)/mL. This intervention not only augmented the microbial density but also modified the metabolite composition of fermented milk, resulting in an elevated presence of advantageous flavor compounds such as nonanal, 2,3-pentanedione, and 3-methyl-2-butanone. However, its influence on improving the texture of fermented milk was observed to be minimal. Co-fermentation of L. salivarius CCFM 1266 with commercial fermentation starters indicated that L. salivarius CCFM 1266 was compatible, similarly altering metabolite composition and increasing niacin content in fermented milk. In summary, the findings suggest that L. salivarius CCFM 1266 holds substantial promise as an adjunctive fermentation starter, capable of enhancing the nutritional diversity of fermented milk products.PMID:38823823 | DOI:10.1016/j.foodres.2024.114309

J Biol Chem. 2024 May 30:107426. doi: 10.1016/j.jbc.2024.107426. Online ahead of print.ABSTRACTSkeletal muscle is heterogeneous tissue, composed of fast-twitch fibers primarily relying on glycolysis and slow-twitch fibers primarily relying on oxidative phosphorylation (OXPHOS). The relative expression and balance of glycolysis and oxidative phosphorylation in skeletal muscle are crucial for muscle growth and skeletal muscle metabolism. Here, we employed multi-omics approaches including transcriptomics, proteomics, phosphoproteomics, and metabolomics to unravel the role of circMYLK4, a differentially expressed circRNA in fast and slow-twitch muscle fibers, in muscle fiber metabolism. We discovered that circMYLK4 inhibits glycolysis and promotes mitochondrial oxidative phosphorylation. Mechanistically, circMYLK4 interacts with the voltage-gated calcium channel auxiliary subunit CACNA2D2, leading to the inhibition of Ca2+ release from the sarcoplasmic reticulum. The decrease in cytoplasmic Ca2+ concentration inhibits the expression of key enzymes, PHKB and PHKG1, involved in glycogen breakdown, thereby suppressing glycolysis. On the other hand, the increased fatty acid β-oxidation enhances the tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation. In general, circMYLK4 plays an indispensable role in maintaining the metabolic homeostasis of skeletal muscle.PMID:38823637 | DOI:10.1016/j.jbc.2024.107426

Biochimie. 2024 May 30:S0300-9084(24)00124-X. doi: 10.1016/j.biochi.2024.05.022. Online ahead of print.ABSTRACTListeria monocytogenes is a human opportunistic foodborne pathogen that produces life-threatening infections with a high mortality rate. The control of Listeria in the food production environment and effective clinical management of human listeriosis are challenging due to the emergence of antibiotic resistance. Hence we evaluate the in vitro anti-Listeria activity of two synthetic cruzioseptins reproducing their natural sequences CZS-9, and CZS-12, and one engineered sequence based on CZS-1, named [K4K15]CZS-1. The assessment of the in vitro potential of cruzioseptins, highlighted the promising antibacterial effect of [K4K15]CZS-1 in very low concentrations (0.91 μM) and its thermal stability at high-temperature conditions, is compatible with the food industry. Microscopic and metabolomic analyses suggest cruzioseptin induces anti-Listeria bioactivity through membrane disruption and changes in the intracellular metabolome. We also report that [K4K15]CZS-1 is resistant to peptidases/proteases emphasizing a key advantage for their use as a food preservative. However, there is a need for further structural and functional optimisations for the potential clinical application as an antibiotic. In conclusion, [K4K15]CZS-1 stand out as membrane-active peptides with the ability to induce shifts in the bacteria metabolome and inspire the development of strategies for the prevention of L. monocytogenes emergence and dissemination.PMID:38823620 | DOI:10.1016/j.biochi.2024.05.022

Chem Biol Interact. 2024 May 30:111089. doi: 10.1016/j.cbi.2024.111089. Online ahead of print.ABSTRACTRadio-resistant triple negative breast cancer (TNBC) is resistant to conventional drugs and radiation therapy. ortho-topolin riboside (oTR) has been evaluated for its anticancer activity in several types of cancer cells. However, its anti-proliferative activity in radio-resistant TNBC cells has not yet been reported. Therefore, we investigated the anti-proliferative activity of oTR in radio-resistant TNBC cells, and performed metabolome, lipidome, transcriptome, and proteome profiling to reveal the mechanisms of the anticancer activity of oTR. oTR showed cytotoxicity against radio-resistant TNBC cells with an inhibitory concentration (IC50) value of 7.78 μM. Significantly decreased (p value < 0.05) basal and compensatory glycolysis were observed in the oTR-treated group than untreated group. Mitochondrial spare respiratory capacity, which is relevant to cell fitness and flexibility, was significantly decreased (p value < 0.05) in the oTR-treated group. The major metabolic pathways significantly altered by oTR according to metabolome, transcriptome, and proteome profiles were the glycerolipid/glycerophospholipid pathway (log2(FC) of MGLL = -0.13, log2(FC) of acylglycerol lipase = -1.35, log2(FC) of glycerol = -0.81), glycolysis (log2(FC) of EGLN1 = 0.16, log2(FC) of EGLN1 = 0.62, log2(FC) of glucose = -0.76, log2(FC) of lactate = -0.81), and kynurenine pathway (log2(FC) of KYNU = 0.29, log2(FC) of kynureninase = 0.55, log2(FC) of alanine = 0.72). Additionally, proline metabolism (log2(FC) of PYCR1 = -0.17, log2(FC) of proline = -0.73) was significantly altered in the metabolomic and transcriptomic profiles. The MAPK signaling pathway (log2(FC) of CCN1 = -0.15, log2(FC) of CCN family member 1 = -1.02) and Rap 1 signaling pathway (log2(FC) of PARD6B = -0.28, log2(FC) of PAR6B = -3.13) were also significantly altered in transcriptomic and proteomic profiles. The findings of this study revealed that oTR has anticancer activity in radio-resistant TNBC cells by affecting various metabolic pathways, suggesting the potential of oTR as a novel anticancer agent for radio-resistant TNBC patients.PMID:38823535 | DOI:10.1016/j.cbi.2024.111089

Protist. 2024 May 23;175(4):126044. doi: 10.1016/j.protis.2024.126044. Online ahead of print.ABSTRACTOver the past decade, the autotrophic and heterotrophic protist Euglena gracilis (E. gracilis) has gained popularity across the studies of environmental science, biosynthesis experiments, and nutritional substitutes. The unique physiology and versatile metabolism of E. gracilis have been a recent topic of interest to many researchers who continue to understand the complexity and possibilities of using E. gracilis biomolecule production. In this review, we present a comprehensive representation of recent literature outlining the various uses of biomolecules derived from E. gracilis across the fields of natural product biosynthesis, as a nutritional substitute, and as bioremediation tools. In addition, we highlight effective strategies for altering metabolite production using abiotic stressors and growth conditions. To better understand metabolite biosynthesis and its role in E. gracilis, integrated studies involving genomics, metabolomics, and proteomics should be considered. Together, we show how the ongoing advancements in E. gracilis related research continue to broaden applications in the biosynthetic sector and highlight future works that would strengthen our understanding of overall Euglena metabolism.PMID:38823247 | DOI:10.1016/j.protis.2024.126044

Food Chem. 2024 May 22;454:139798. doi: 10.1016/j.foodchem.2024.139798. Online ahead of print.ABSTRACTIngestion of fermented foods impacts human immune function, yet the bioactive food components underlying these effects are not understood. Here, we interrogated whether fermented food bioactivity relates to microbial metabolites derived from aromatic amino acids, termed aryl-lactates. Using targeted metabolomics, we established the presence of aryl-lactates in commercially available fermented foods. After pinpointing fermented food-associated lactic acid bacteria that produce high levels of aryl-lactates, we identified fermentation conditions to increase aryl-lactate production in food matrices up to 5 × 103 fold vs. standard fermentation conditions. Using ex vivo reporter assays, we found that food matrix conditions optimized for aryl-lactate production exhibited enhanced agonist activity for the human aryl-hydrocarbon receptor (AhR) as compared to standard fermentation conditions and commercial products. Reduced microbial-induced AhR activity has emerged as a hallmark of many chronic inflammatory diseases, thus we envision strategies to enhance AhR bioactivity of fermented foods to be leveraged to improve human health.PMID:38823201 | DOI:10.1016/j.foodchem.2024.139798

Int Immunopharmacol. 2024 May 31;136:112370. doi: 10.1016/j.intimp.2024.112370. Online ahead of print.ABSTRACTReperfusion after myocardial ischemia would aggravate myocardial structural and functional damage, known as myocardial ischemia-reperfusion (MI/R) injury. Cinnamamide derivatives have been reported to exert cardioprotective effects, and we have previously reported that compound 7 played a role in cardioprotection against MI/R via anti-inflammatory effect. However, exact mechanism underlying such beneficial action of compound 7 is still unclear. The protective effect of compound 7 was determined in H9c2 cells under H2O2 stimulation with or without nigerin (NLRP3 activator). Electrocardiogram, echocardiography, myocardial infarction size, histopathology and serum biochemical assay were performed in MI/R rats. Metabolomics in vivo and mRNA or protein levels of NLRP3, ASC, cleaved caspase-1 and its downstream IL-18 and IL-1β were detected both in vitro and in vivo. Compound 7 significantly ameliorate H2O2-induced cardiomyocyte damage, which was supported by in vivo data determined by improved left ventricular systolic function and histopathological changes, reduced myocardial infarction area and cellular apoptosis in heart tissue. Cardiac differential metabolites demonstrated that compound 7 indeed altered the cardiac reprogramming of inflammation-related metabolites, which was evidenced by down-regulated cardiac inflammation by compound 7. Additionally, compound 7 alleviated myocardial injury by inhibiting the NLRP3 pathway rather than other members of the inflammasome both in vitro and in vivo, which was further evidenced by CETSA assay. Whereas, nigerin blocked the inhibitory activity of compound 7 against NLRP3. Cinnamamide derivative compound 7 ameliorated MI/R injury by inhibiting inflammation via NLRP3.PMID:38823174 | DOI:10.1016/j.intimp.2024.112370

Food Chem. 2024 May 27;455:139857. doi: 10.1016/j.foodchem.2024.139857. Online ahead of print.ABSTRACTMelatonin acts as a potential regulator of cadmium (Cd) tolerance in rice. However, its practical value in rice production remains unclear. To validate the hypothesis that melatonin affects Cd accumulation and rice quality, a series of experiments were conducted. The results showed that exogenous melatonin application was associated with reduced Cd accumulation (23-43%) in brown rice. Fourier transform infrared spectroscopy (FTIR) analysis showed that exogenous melatonin affected the rice protein secondary structure and starch short-range structure. Metabolomics based on LC-MS/MS revealed that exogenous melatonin altered the brown rice metabolic profile, decreased fatty acid metabolite content, but increased amino acid metabolite, citric acid, melatonin biosynthetic metabolite, and plant hormone contents. These findings indicate that exogenous melatonin can effectively reduced Cd accumulation and improve rice quality through metabolic network regulation, serving as an effective treatment for rice cultivated in Cd-contaminated soil.PMID:38823141 | DOI:10.1016/j.foodchem.2024.139857

Plant Physiol Biochem. 2024 May 22;212:108770. doi: 10.1016/j.plaphy.2024.108770. Online ahead of print.ABSTRACTCadmium (Cd) and lead (Pb) are among the most toxic heavy metals affecting human health and crop yield. Suaeda maritima (L.) Dumort is an obligate halophyte that is well adapted to saline soil. The inbuilt salinity tolerance mechanisms of halophytes help them to survive in heavy metal-contaminated rhizospheric soil. In the present study, growth and ionomic responses, reactive oxygen species (ROS) accumulation, modulations of phytochelatins, antioxidative defense, and metabolomic responses were studied in S. maritima imposed to Cd and Pb stresses with an aim to elucidate Cd and Pb tolerance mechanisms and phytoremediation potential of this halophyte. Our results showed a reduction of biomass in S. maritima, which may serve as an energy conservation strategy for survival under heavy metal stress. The increased accumulation of ROS with concomitant higher expression of various antioxidative enzymes suggests the efficient scavenging of ROS. The metabolite profiling revealed significant up-regulation of sugars, sugar alcohols, amino acids, polyphenols, and organic acids under Cd and Pb stresses suggesting their possible role in osmotic balance, ionic homeostasis, ROS scavenging, and signal transduction for stress tolerance. In S. maritima, the translocation factors (Tf) are <1 in both Cd and Pb treatments, which indicates that this halophyte has high phytostabilization potential for Cd and Pb in roots and through restricted translocation of heavy metal ions to the aboveground part. The findings of this study offer comprehensive information on Cd and Pb tolerance mechanisms in S. maritima and suggest that this halophyte can detoxify the HMs through physiological, ionic, antioxidative, and metabolic regulations.PMID:38823092 | DOI:10.1016/j.plaphy.2024.108770

J Anim Sci Biotechnol. 2024 Jun 1;15(1):71. doi: 10.1186/s40104-024-01034-3.ABSTRACTBACKGROUND: The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce, particularly regarding dietary interventions. Therefore, our study undertook a comprehensive analysis, incorporating both metabolomics and transcriptomics, to explore the effects of a grain-based diet on the functionality of the hypothalamus, as well as on blood and milk in dairy cows.RESULTS: The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E2 (PGE2) level as a prominent response to the grain-based diet introduction. Furthermore, the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet. Conversely, the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE2, including phospholipase A2 (PLA2G4E, PLA2G2A, and PLA2G12B), cyclooxygenase-2 (COX2), and prostaglandin E synthase (PTGES). Additionally, the plasma metabolome analysis indicated a substantial decrease in the level of PGE2, along with a decline in adrenal steroid hormones (tetrahydrocortisol and pregnenolone) following the grain-based diet introduction. Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE2 level. Importantly, PGE2 was identified as a critical metabolic marker in the hypothalamus, blood, and milk in response to grain intervention. Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus, blood, and milk following the grain-based diet.CONCLUSIONS: Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet.PMID:38822422 | DOI:10.1186/s40104-024-01034-3