PubMed

Anim Nutr. 2024 Aug 31;19:192-214. doi: 10.1016/j.aninu.2024.08.002. eCollection 2024 Dec.ABSTRACTWith the increasing incorporation of plant-based ingredients into the grouper diet, the issue of aflatoxin B1 (AFB1) contamination in the diet has become a significant concern. In this study, the negative effects of AFB1 on the growth and liver health of hybrid groupers (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂) were investigated in the context of growth, liver histology, serum biochemical indices, and integrated transcriptomic and metabolomic data. A total of 540 healthy hybrid groupers, initially weighing 11.59 ± 0.03 g, were randomly divided into six groups (three replicates of 30 fish each): the control group was fed a basal diet, and the experimental groups were supplemented with 7 (AF7), 30 (AF30), 111 (AF111), 445 (AF445) and 2230 μg/kg AFB1 (AF2230) in the basal diet respectively, for 56 days. Groups control, AF445, and AF2230 were selected for subsequent histological, muscle fatty acid, and transcriptomic and metabolomic analyses based on the results of hybrid grouper growth and serum biochemical indices. Compared to the control group, both whole-body crude lipid and muscle crude lipid contents showed significant decreases in the AF2230 group (P < 0.05), while only muscle crude lipid content showed a significant decrease in the AF445 group (P = 0.001). Liver damage was seen in the histology of the liver of AF445 and AF2230 groups. Muscle fatty acid results showed that the addition of 445 and 2230 μg/kg AFB1 to the diets increased saturated fatty acids and monounsaturated fatty acids and decreased polyunsaturated fatty acids and highly unsaturated fatty acids in muscle (P < 0.05). Transcriptome analyses revealed multiple metabolic pathways associated with AFB1 metabolism, and metabolomics analyses further confirmed changes in the activity of these pathways. The results of the combined transcriptomic and metabolomic analyses indicated that AFB1 causes liver injury mainly by affecting liver retinol metabolism, metabolism of xenobiotics by cytochromes P450, drug metabolism-cytochromes P450 and biosynthesis of unsaturated fatty acids. In conclusion, dietary AFB1 levels above 445 μg/kg resulted in growth inhibition, liver injury, liver AFB1 accumulation, and reduced muscle polyunsaturated fatty acid content in groupers, thereby affecting muscle quality. This study provides novel insights into the detrimental effects of AFB1 on aquatic species and contributes to the scientific basis for the health and sustainability of aquaculture practices.PMID:39640554 | PMC:PMC11617246 | DOI:10.1016/j.aninu.2024.08.002

Anim Nutr. 2024 Jul 17;19:386-400. doi: 10.1016/j.aninu.2024.04.025. eCollection 2024 Dec.ABSTRACTDelivery and weaning are major stressful events in sows and piglets, adversely affecting production and growth performance and causing economic losses to swine farms. Probiotics as safe antibiotic alternatives have great potential for use across all stages of livestock farming. Here, 18 pregnant sows from clinical farms randomly were divided into two groups: one fed a basal diet (CON group) and the other fed a basal diet plus a probiotic mixture CBB-mix (containing 1×1012 CFU/g of Lactobacillus johnsonii [CJ21], 1×109 CFU/g of Bacillus subtilis [BS15], and 1×109 CFU/g of Bacillus licheniformis [BL21]), for 20 days before delivery. The effects of maternal CBB-mix supplementation on sow colostrum metabolome and offspring piglets' clinical performance, immune status, and gut microbiota were investigated. Additionally, 177 piglets were randomly divided into 4 groups, including CC group (piglets and sows fed a basal diet, n = 40 from 5 litters), CP group (piglets fed the basal diet plus CBB-mix and sows fed the basal diet, n = 38 from 4 litters), PC group (piglets fed the basal diet and sows fed the basal diet plus CBB-mix, n = 50 from 4 litters), and PP group (both piglets and sows fed the basal diet plus CBB-mix, n = 49 from 5 litters). Among that, CP and PP groups were added CBB-mix in the creep feed from 11 days of age for 18 days to study the direct effects of CBB-mix on the growth performance of piglets. Maternal CBB-mix supplementation improved sow production performance, including litter size at birth and litter weight at birth (P < 0.05). Piglets born from CBB-mix-fed sows exhibited increased litter size at weaning and reduced diarrhea incidence from 1 to 10 days of age (P < 0.05). Additionally, systemic immune status and antioxidant capabilities were improved in both sows and piglets. Maternal CBB-mix supplementation reconstituted the gut microbiota structure and increased the Sobs index and Shannon index of fecal microbiota in both sows and piglets (P < 0.05). The relative abundance of Firmicutes and Clostridium_sensu_stricro_1 in sow feces was decreased after feeding CBB-mix (P < 0.05). In piglets, 10-day-old feces had relatively more Lactobacillus but less Escherichia-Shigella than 1-day-old feces (P < 0.05), indicating that maternal feeding CBB-mix alone affects the gut microbiota community of offspring piglets via the gut-breast axis. Piglets born from CBB-mix-fed sows had continuously decreased the relative abundance of fecal Escherichia-Shigella at 28 days of age (P < 0.05). Consistently, the metabolite profile in sow milk was also changed by CBB-mix. Colostrum metabolome showed that CBB-mix significantly regulated tryptophan metabolism and primary bile acid biosynthesis. Our data demonstrated that maternal CBB-mix supplementation effectively improved the production performance of sows and their offsprings' growth performance. Through the gut-breast axis (interaction between gut microbiota and mammary glands), feeding CBB-mix to sows impacted the gut microbiota of their offspring. This study provides strategy and evidence for maternal probiotic supplementation to improve immune status and gut microbiota homeostasis in response to delivery and weaning.PMID:39640549 | PMC:PMC11617873 | DOI:10.1016/j.aninu.2024.04.025

Anim Nutr. 2024 Aug 18;19:355-369. doi: 10.1016/j.aninu.2024.04.023. eCollection 2024 Dec.ABSTRACTProbiotics have beneficial effects on improving egg quality, but there is little research about the effect of probiotics on metabolite composition, and the mechanisms are not yet fully understood. The aim of this study was to investigate the potential mechanisms by which compound Bacillus improves egg quality and metabolite composition. A total of 20,000 Jingfen No. 6 laying hens at 381 d old were randomly divided into two treatments: control group with a basal diet, and the basal diet with 5 × 108 CFU/kg compound Bacillus supplementation (Ba) group. The trial lasted eight weeks. The results showed that compound Bacillus improved the gloss and strength of eggshells and reduced the ratio of sand-shell eggs by 23.8%. Specifically, the effective layer of eggshell was thicker and its calcite column was closely connected. Compound Bacillus increased the contents of beneficial fatty acids in the egg yolk, and lipids and lipid-like molecules in the albumen (P < 0.01), while decreased the contents of total cholesterol, triglycerides, and benzene ring compounds in the egg yolk and organic oxygen compounds in the albumen (P < 0.01). In addition, the compound Bacillus increased the calcium absorption in the duodenum by up-regulating the expression of transporters and serum hormone synergism (P < 0.05), and promoted metabolic balance of calcium and phosphorus. Simultaneously, uterine transcriptome showed that the expression of ChaC glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1), glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1 (C1GALT1), phosphatidylinositol-4-phosphate 5-kinase type 1 beta (PIP5K1B), methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), brain enriched myelin associated protein 1 (BCAS1), and squalene epoxidase (SQLE) genes were increased (P < 0.01), indicating that nutrient metabolism activity was enhanced. The expression of the BCAS1, C1GALT1, KLF transcription factor 13 (KLF13), and leucine rich repeat neuronal 1 (LRRN1) was increased (P < 0.01), indicating that the cell proliferation was enhanced, which slowed uterus aging. In conclusion, compound Bacillus improved the eggshell strength and metabolite composition in the egg by promoting metabolic balance of calcium and phosphorus, cell proliferation, and nutrient metabolism in the uterus.PMID:39640545 | PMC:PMC11617893 | DOI:10.1016/j.aninu.2024.04.023

Front Pharmacol. 2024 Nov 21;15:1489834. doi: 10.3389/fphar.2024.1489834. eCollection 2024.ABSTRACTINTRODUCTION: Diabetic cognitive impairment(DCI) presents as a central nervous complication of diabetes especially among aging population. Melatonin (MEL) is known for its antioxidant and anti-inflammation effects in neuroprotective aspects. Recent evidence has demonstrated that the gut microbiome plays a key role in DCI by modulating cognitive function through the gut-brain crosstalk. MEL has been shown to modulate gut microbiota composition in diabetic model. However, the underlying mechanism through which the gut microbiome contributes to DCI remains unclear. This study aims to investigate the effect and mechanism of MEL in attenuating DCI in relation to regulating the gut microbiome and metabolomics.METHODS: Cognitive and memory function were assessed by the Morris water maze test, histopathological assessment of brain tissues, and immunoblotting of neuroinflammation and apoptosis. The levels of serum tumor necrosis factor-α (TNF-α) and Interleukin-18 (IL-18) were measured by enzyme-linked immunoassays to reflect the circulatory inflammation level.16S rRNA microbiome sequencing analysis was performed on control mice(db-m group), diabetic mice(db-db group) and MEL-treated diabetic mice(db-dbMEL group). Gut metabolites changes were characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS).RESULTS: Our study confirmed that MEL alleviated diabetes-induced cognition and memory dysfunction. MEL protected against neuroinflammation and apoptosis in hippocampus of db-db mice. MEL corrected the increased abundance of Bacteroides and Dorea and the reduced abundance of Prevotella in db-db mice. The vast majority of differential metabolites among the three groups were lipids and lipid-like molecules. MEL significantly restored the reduced levels of pyruvate and lactic acid.DISCUSSION: Our results supported the use of MEL as a promising therapeutic agent for DCI, in which the underlying mechanism may be associated with gut microbiome and metabolomics regulation.PMID:39640487 | PMC:PMC11619431 | DOI:10.3389/fphar.2024.1489834

Front Pharmacol. 2024 Nov 20;15:1467132. doi: 10.3389/fphar.2024.1467132. eCollection 2024.ABSTRACTBACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has grown to become the dominant form of heart failure worldwide. However, no unequivocally effective treatment for HFpEF has been identified in clinical trials. In this study, we report that Astragaloside IV (AS-IV) can be used to treat HFpEF.METHODS: Mice were fed on a high-fat diet and given 0.5 g/L L-NAME (in drinking water) for 10 weeks to establish the HFpEF model. After 10th weeks, the HFpEF mice were given 10 mg/kg empagliflozin, 10 mg/kg AS-IV, or 20 mg/kg AS-IV for 4 weeks. The echocardiography, blood pressure, hemodynamics, heart failure biomarkers, collagen deposition and fibrosis, histopathology, and inflammation in HFpEF mice were evaluated. Metabolic profiling based on NMR measurements was also performed. Myocardial glucose and fatty acid metabolism were evaluated.RESULTS: AS-IV improves cardiac function and myocardial remodeling in HFpEF mice. AS-IV attenuates systemic inflammatory infiltration and myocardial inflammation levels in HFpEF mice by decreasing the expression of plasma inflammatory markers GDF15, CRP, IL1RL1, and MCP-1, NLRP3, IL-1β, Caspase-1, and IL-6 in the myocardium of HFpEF mice. Metabolomic analysis suggested that AS-IV improved cardiac glucose and fatty acid metabolism in HFpEF mice. Further studies showed that AS-IV significantly improved Complex I activity, increased ATP production, and elevated plasma NAD + levels; AS-IV also significantly improved pyruvate dehydrogenase activity and decreased pyruvate and lactate accumulation, thereby improving glucose metabolism in the hearts of HFpEF mice.CONCLUSION: These results provide novel evidence that Astragaloside IV alleviates inflammation and improves myocardial metabolism in HFpEF mice.PMID:39640484 | PMC:PMC11618538 | DOI:10.3389/fphar.2024.1467132

Drug Des Devel Ther. 2024 Nov 30;18:5485-5500. doi: 10.2147/DDDT.S491970. eCollection 2024.ABSTRACTBACKGROUND: Acute myocardial infarction (AMI) is a significant clinical challenge. Semaglutide has therapeutic potential in cardiovascular disease management, but its specific impact and mechanisms in AMI are not fully understood.METHODS: Twenty-four male Sprague-Dawley rats were divided into three groups: control (Control), infarction-only (MI), and semaglutide-treated (SEMA). Weight, blood glucose, and lipid profiles were analyzed. Cardiac function was evaluated via echocardiography. Histopathological assessment and immunohistochemical analysis were performed. Untargeted metabolomic analysis using LC-MS/MS was utilized.RESULTS: Semaglutide treatment was associated with a reduction in body weight, blood glucose, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), as well as an enhancement in the left ventricular ejection fraction (Control vs MI vs SEMA, 69.13±4.30 vs 30.16±3.17 vs 39.81±6.13, P < 0.05). It also had a lower collagen volume fraction (3.05 vs 34.05 vs 17.73, P < 0.05) and ameliorated the accumulation of glycogen in the myocardium. Metabolomic profiling revealed differentially expressed metabolites between the control/MI and MI/SEMA groups, predominantly within benzenoid, lipid, and organic acid categories. Pathway enrichment analysis highlighted amino sugar and nucleotide sugar metabolism, chlorocyclohexane and chlorobenzene degradation, and phenylalanine, tyrosine, and tryptophan biosynthesis. Random forest analysis identified key metabolites, including downregulated Docusate sodium, 1-(2-Thienyl)-1-heptanone, and Adenylyl-molybdopterin, alongside upregulated Methylenediphosphonic acid, Choline sulfate, and Lactosamine.CONCLUSION: Semaglutide significantly ameliorated myocardial fibrosis and metabolic dysregulation in rats post-myocardial infarction. Its mechanism involves modulating glucose metabolism, lipid metabolism, and organic acid metabolism. Targeted metabolites, including Docusate sodium, 1-(2-Thienyl)-1-heptanone, Adenylyl-molybdopterin, Methylenediphosphonic acid, Choline sulfate, and Lactosamine, are implicated in the metabolic reprogramming induced by semaglutide.PMID:39640291 | PMC:PMC11618856 | DOI:10.2147/DDDT.S491970

Synth Syst Biotechnol. 2024 Nov 8;10(1):262-270. doi: 10.1016/j.synbio.2024.11.002. eCollection 2025.ABSTRACTNatural products (NPs) afforded by living-beings, especially by microscopic species, represent invaluable and indispensable reservoirs for drug leads in clinical practice. With the rapid advancement in sequencing technology and bioinformatics, the ever-increasing number of microbial biosynthetic gene clusters (BGCs) were decrypted, while a great deal of BGCs remain cryptic or inactive under standard laboratory culture conditions. Addressing this dilemma requires innovative tactics to awaken quiescence of BGCs by releasing the potential of microbial secondary metabolism for mining novel NPs. In this study, a universal strategy was proposed to induce the expression of silent BGCs by leveraging the dynamic interactions among coexisting microbial neighbors within a microbiota. This approach involves the deconstruction/reconstruction of binary interactions among the coexisting neighbors to create a pipeline for BGCs arousing. Coupled with the acquisition of 2760 microbial individuals from the Apocynum venetum (Luobuma, LBM) phyllosphere in a successive dilution procedure, 44 culturable isolates were screened using binary interaction, in which 12.6 % pairs demonstrated potent mutual interacting effects. Furthermore, after selecting the four most promising isolates, a full-scale metabolic inspection was conducted, in which 25.3 % of the interacting pairs showcased significant metabolomic variations with de-cryptic activities. Notably, with the aid of visualization of IMS technology, one of the physiologically functional entities, the bactericidal agent resistomycin, was elucidated from the core interacting pair between the co-culture of the Streptomyces sp. LBM_605 and the Rhodococcus sp. LBM_791. This study highlights the intrinsic interactions among coexisting microorganisms within a phyllosphere microbiota as novel avenues for exploring and harnessing NPs.PMID:39640290 | PMC:PMC11617933 | DOI:10.1016/j.synbio.2024.11.002

Microb Cell Fact. 2024 Dec 5;23(1):328. doi: 10.1186/s12934-024-02567-y.ABSTRACTBACKGROUND: In the search for new antimicrobial secondary metabolites of fungi, optimizing culture conditions remains a critical challenge, as standard laboratory approaches often result in low yields. While non-selective methods, such as modifying culture media, have been effective in expanding the chemical diversity of fungal metabolites, they have not yet established a direct link to key process parameters crucial for further optimization. This study investigates the capacity of Diaporthe caliensis as a biofactory for biologically active secondary metabolites, employing tailored culture media to explore the relationship between chemical diversity and critical process variables.RESULTS: The metabolomic profiles, antibacterial activities, and production yields of the extracts were analyzed to progressively adjust the culture conditions. This study was conducted in five steps, evaluating carbon and nitrogen source concentration, nitrogen source type, salt supplementation, and pH adjustment. Altering the rice starch concentration affected biomass yield per unit of oxygen consumed, while modifications to the nitrogen source concentration influenced both the bioactivity and chemical space by Diaporthe caliensis. Despite changes at the metabolome level, the extracts consistently exhibited potent antibacterial activities, influenced by the nitrogen source, added salts and pH adjustments. For instance, when using corn steep liquor and rice starch, supplemented with micronutrients, different metabolites were produced depending on whether buffer or water was used, though both conditions showed similar antibacterial activities (IC50 ≈ 0.10 mg mL- 1 against Staphylococcus aureus and ≈ 0.14 mg mL- 1 against Escherichia coli). In the treatment where buffer was used to stabilize pH change, there was an increase in the production of phomol-like compounds which are associated with known antibiotic properties. In contrast, in the treatments using water, the drop in pH stimulated the production of previously unidentified metabolites with potential antimicrobial activity.CONCLUSIONS: This study proposes a strategic methodology for the tailored formulation of culture media aiming to promote the biosynthesis of diverse secondary metabolites. This approach revealed the critical role of nutrient limitation and pH regulation in stimulating the production of polyketide-lactone derivatives, including the antibiotic phomol. Ultimately, the systematic, custom-designed culture conditions developed in this work offer a promising strategy for expanding the chemical diversity of Diaporthe caliensis, while providing valuable insights into the key parameters needed for optimizing this fungal biofactory.PMID:39639292 | DOI:10.1186/s12934-024-02567-y

Sci Rep. 2024 Dec 5;14(1):30344. doi: 10.1038/s41598-024-82260-7.ABSTRACTAbnormal feeding behaviors and inadequate nutrient intake of children with autism spectrum disorder (ASD) have been reported. This study aimed to examine the plasma vitamin status of boys with autism spectrum disorder (ASD) and to analyze the association between vitamin status and symptoms of ASD. A total of 45 boys with ASD (age = 3.25 ± 0.68 years) and 45 typically developing (TD) boys (age = 3.33 ± 0.66 years) were enrolled. The developmental levels were evaluated using the Gesell Developmental Schedules (GDS), the severity of ASD was evaluated using the Childhood Autism Rating Scale (CARS). The plasma vitamin levels were determined using metabolomics method. The Vitamin B1, nicotinamide, pyridoxamine dihydrochloride and Vitamin E were found to be significantly higher in the boys with ASD compared with those without ASD. In addition, no significant differences in vitamin metabolic pathways were found between the ASD group and the TD group.The nicotinamide and pyridoxamine dihydrochloride concentration were found to be negatively correlated with GDS score. In comparison with TD boys, the plasma vitamin concentration of ASD boys was not insufficient. Further studies are required to investigate whether it is necessary to use vitamin nutritional supplements in children with ASD.PMID:39639123 | DOI:10.1038/s41598-024-82260-7

Fish Physiol Biochem. 2025 Feb;51(1):1-18. doi: 10.1007/s10695-024-01417-3. Epub 2024 Dec 6.ABSTRACTCreatine is a feed additive with physiological pleiotropic properties and also an energy homeostasis protector in vertebrates and is successfully used in terrestrial livestock and aquaculture. Here, two feeding trials were performed to investigate dietary creatine on endogenous creatine metabolism and physiological reprogramming in largemouth bass. The results showed that the endogenous creatine metabolism genes AGAT, GAMT, and SLC6A8 of largemouth bass are highly conserved with the amino acid sequences of other teleosts and are clustered separately from mammals. Among the 16 major tissues in largemouth bass, both creatine synthesis genes (agat, gamt) and transporter gene slc6a8 are most highly expressed in muscle. Muscle has a high threshold but sensitive creatine negative feedback to regulate endogenous creatine metabolism. Dietary creatine intake significantly inhibits endogenous creatine synthesis and transport in muscle in a dose-dependent manner, and this inhibitory effect recovers with a decrease in dietary creatine content. In addition, physiological creatine saturation required prolonged exogenous creatine intake, and it would be shortened by high doses of creatine, which provides guidance for maximizing economic benefits in aquaculture. Metabolome and transcriptome showed that dietary creatine significantly affected the metabolism of the creatine precursor substance-arginine. Exogenous creatine intake spared arginine that would otherwise be used for creatine synthesis, increased arginine levels, and caused reprogramming of arginine metabolism. Overall, these results demonstrate that the addition of creatine to largemouth bass diets is safe and recoverable, and the benefits of creatine intake in largemouth bass are not limited to enhancing the function of creatine itself but also include a reduction in the metabolic burden of essential amino acids to better growth performance.PMID:39638990 | DOI:10.1007/s10695-024-01417-3

Cell Res. 2024 Dec 6. doi: 10.1038/s41422-024-01053-9. Online ahead of print.NO ABSTRACTPMID:39638924 | DOI:10.1038/s41422-024-01053-9

Sci Rep. 2024 Dec 5;14(1):30357. doi: 10.1038/s41598-024-81946-2.ABSTRACTSpodoptera litura (S. litura) is a polyphagous pest of the family Lepidoptera, which causes damage and yields losses to many crops. The long-term use of chemical pesticides for control not only seriously threatens environmental health, but also causes S. litura to develop drug resistance. Therefore, there is an urgent need to develop environmentally safe and friendly biogenic pesticides. However, the mechanism of action of the secondary metabolite (surfactin) of Bacillus Vélezensis (B. vélezensis) on lepidopteran pests (S. litura) has not been reported yet. We found that several metabolites and genes in S. litura were affected by surfactin exposure. The expressions of the metabolites (protoporphyrinogen (PPO), gluconolactone (GDL), and L-cysteate) were significantly down-regulated while glutamate and hydroxychloroquine were significantly up-regulated. The expression levels of genes related to drug metabolism and detoxification, include the glutathione s-transferase (GST) gene family and acetaldehyde dehydrogenase (ALDH), and apoptosis-inhibiting genes (seven in absentia homolog 1(SIAH1)) were significantly decreased. In addition, pathological changes occurred in intestinal wall cells, Malpighian tubule cells, and nerve cells of S. litura under surfactin stress. Conclusively, our results suggest that surfactin induces an increase in reactive oxygen species (ROS) and damages S. litura cells. Furthermore, based on the integrated analysis of transcriptomic and metabolomic data, it is hypothesized that surfactin may also trigger neurotoxicity and cardiotoxicity in S. litura while hindering the insect's detoxification processes. This study lays a foundation for further exploration of surfactin as a potential biopesticide.PMID:39638883 | DOI:10.1038/s41598-024-81946-2

Sci Rep. 2024 Dec 5;14(1):30379. doi: 10.1038/s41598-024-81611-8.ABSTRACTHypertension-induced myocardial remodelling encompasses both structural and functional changes in cardiac muscle tissue, such as myocardial hypertrophy, fibrosis, and inflammation. These alterations not only impair the systolic and diastolic functions of the heart but also elevate the risk of cardiovascular events and heart failure. One of the primary contributors to hypertensive cardiomyopathy (HTN-CM) is the over-activation of the renin-angiotensin-aldosterone system (RAAS), which subsequently induces myocardial remodeling. Although conventional therapeutic strategies aim to suppress RAAS and slow the progression of heart failure, the primary challenge in treating HTN-CM remains the lack of sensitive and specific biomarkers for early detection of myocardial remodelling. Combined multi-omics analyses, complemented by experimental validation, offer a systematic understanding of the landscape of gene/protein/metabolite expression in HTN-CM, revealing the underlying mechanisms of angiotensin II (Ang II)-induced myocardial remodeling in HTN-CM. Transcriptomic analysis revealed that differentially expressed genes (DEGs) are implicated in sphingolipid metabolic processes and are associated with collagen synthesis and inflammatory responses, collectively contributing to myocardial remodeling in HTN-CM. Proteomic analysis demonstrated that differentially expressed proteins (DEPs) are also involved in inflammatory and fibrotic processes, with associations to sphingolipid signaling pathways, particularly manifested through elevated expression of IL6, COL4A1, FGG, FGB, CREBBP and SPHK2 proteins. Metabolomic profiling further elucidated the increased expression of bioactive sphingolipid metabolites S1P and Sa1P in the myocardium of HTN-CM. Integrative multi-omics analysis revealed that HTN-CM is primarily influenced by the sphingolipid signaling pathway, with additional associations to the HIF-1α and FoxO signaling pathways. Correlation analysis has highlighted strong associations between sphingolipids and genes/proteins related to fibrosis and inflammation, as well as their connection to the HIF-1α and FoxO signalling pathways. Furthermore, certain key indicators were validated through ELISA and Western blot analyses in both plasma and myocardial tissue. In conclusion, the findings of this study suggest that excessive Ang II may induce abnormalities in sphingolipid metabolism, resulting in increased levels of S1P in both circulating and myocardial tissues. This elevation in S1P is implicated in myocardial inflammatory and fibrotic alterations, highlighting its pivotal role in myocardial remodeling. The specific mechanism underlying the sphingolipid signaling pathway in myocardial remodeling may involve downstream biological processes, including oxidative stress and excessive mitochondrial autophagy, mediated by HIF-1α and FoxO.PMID:39638825 | DOI:10.1038/s41598-024-81611-8

Chem Biodivers. 2024 Dec 5:e202401484. doi: 10.1002/cbdv.202401484. Online ahead of print.ABSTRACTRecent episodes of viral pandemics have led to a quest for new drugs to act on emerging targets. Most challenging viruses are only mutants of already known viruses. Here comes the role of metabolomics in investigating natural secondary metabolites as sustainable antiviral drug candidates. Resins are natural plant products having the advantage of being concentrated and consisting of precious terpenoids, phenolics and flavonoids, known for their anti-pathogen activity. This study aimed at investigation of the major phytoconstituents in the Eucalyptus maculata (EM) resin using high resolution LC-MS/MS and investigating its antiviral potential. In vitro screening of the standardized EM antiviral activity was performed. High resolution LC-MS/MS analysis was done for the extract followed by investigation of the possible active metabolites through molecular docking techniques against two viral protein targets; herpes simplex virus glycoprotein D (HSV gD) and BTLA/HVEM complex. The evaluation in negative and positive modes identified 29 substances and revealed the prevalence of coumaryl and galloyl derivatives, in addition to kaempferol and aromadendrin derivatives. Antiviral in-vitro screening led to the conclusion of the promising effect of the resin against HSV which was further confirmed through molecular docking. EM resin represents a future sustainable drug discovery.PMID:39638765 | DOI:10.1002/cbdv.202401484

J Agric Food Chem. 2024 Dec 5. doi: 10.1021/acs.jafc.4c07892. Online ahead of print.ABSTRACTOxidative derivatives of triacylglycerols (ox-TGs), aldehydes, and 3-monochloropropane-1,2-diol esters (3-MCPDE) were simultaneously evaluated in a 90-day subchronic study, focusing on biological indicators, biochemical indicators, and serum metabolomics as the first part of integrated toxicity and interactions. After 90 days of feeding Kunming mice, coexposure to combined toxicants significantly inhibited the trend of liver weight gain, reduced the levels of total bilirubin (TBIL) and direct bilirubin (DBIL), and decreased uric acid (UA) compared to individual toxicant exposure. A total of 21 and 31 biomarkers in female and male mice were identified, respectively. Co-exposure to combined toxicants might mitigate the changes in cytidine, CDP, dUMP, and dUDP involved in purine and pyrimidine metabolism caused by a single exposure, but exacerbate the changes in l-tryptophan, 5-hydroxy-l-tryptophan, and 5-hydroxyindoleacetic acid, which are involved in tryptophan metabolism. These results provided new insights into a comprehensive toxicity and interaction evaluation model of multiple combined toxicants in food.PMID:39638751 | DOI:10.1021/acs.jafc.4c07892

Crit Care Nurs Q. 2025 Jan-Mar 01;48(1):8-14. doi: 10.1097/CNQ.0000000000000540. Epub 2024 Dec 2.ABSTRACTSepsis remains a major concern in health care globally. Despite decades of research, incidence is on the rise, and mortality remains high. Costs are staggering. Additionally, the outdated sepsis bundle established based on SIRS, remains the standard by which providers are held accountable. It is now accepted that organ dysfunction in sepsis is secondary to cellular metabolic dysregulation. Technology for metabolic monitoring should be explored for improved, early recognition of sepsis. We sought to investigate the underlying metabolic profile of patients with sepsis, to determine the value of continuous metabolic monitoring technology. The investigators partnered with industry, to trial noninvasive monitoring of the cellular metabolite carbon dioxide, under a prospective, observational design. During the 6-month trial, the investigators collected data from the electronic medical record of patients using the technology, to determine the specific metabolic differences between patients with and without sepsis. The investigators found serum carbon dioxide (paCO2) was significantly lower in patients with sepsis, and, low paCO2 had a significant inverse relationship to serum lactate. This finding supports the notion that paCO2 is low in sepsis secondary to metabolic dysregulation and not hyperventilation, which had historically explained low paCO2 under the SIRS model. Metabolic monitoring is available, easy to apply and manage, and contributes valuable information in the detection of sepsis. Further research should be done to understand trends in serum CO2 and its relationship to the development of sepsis. This study also provides important further support for the emerging understanding of the dysregulated host response in sepsis.PMID:39638331 | DOI:10.1097/CNQ.0000000000000540

Toxicol Appl Pharmacol. 2024 Dec 3:117187. doi: 10.1016/j.taap.2024.117187. Online ahead of print.ABSTRACTCadmium (Cd) is a toxic heavy metal that has been extensively implicated in disordered folliculogenesis, but the mechanisms underlying the ovarian toxicity of Cd remain to be explored fully. Granulosa cells are key players in ovarian follicular development and are the primary cells affected by Cd exposure-induced damage and dysfunction. In this study, we investigated how various levels of exposure of Cd (3 and 10 μM) to human granulosa cells (KGN cells) impacted the metabolism of the KGN cells utilizing a non-targeted metabolomics methodology. In vitro cell experiments revealed that Cd exposure dose-dependently diminished the viability of KGN cells. Metabolomics analysis revealed the presence of 296 (182 elevated and 114 reduced) and 397 (244 elevated and 153 reduced) differentially expressed metabolites after exposure to 3 and 10 μM, respectively. Cd exposure was found to significantly enrich nucleotide metabolism, sphingolipid metabolism, and ABC transporters in both groups. Although amino acid metabolic pathways exhibited significant enrichment across all groups, only glutathione, cysteine, and methionine metabolism were notably enriched in KGN cells exposed to 3 μM Cd, while glutathione and tryptophan metabolism were significantly enriched in the 10 μM Cd exposure cohort. The outcomes of this study provide mechanistic clues for elucidating Cd's cytotoxic impact on granulosa cells, and deepen our understanding of the ovarian toxicity of Cd.PMID:39638002 | DOI:10.1016/j.taap.2024.117187

Int J Cardiol. 2024 Dec 3:132881. doi: 10.1016/j.ijcard.2024.132881. Online ahead of print.NO ABSTRACTPMID:39637995 | DOI:10.1016/j.ijcard.2024.132881

Biomol Ther (Seoul). 2024 Dec 5. doi: 10.4062/biomolther.2024.086. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) exhibits an altered metabolic profile compared to normal pancreatic tissue. However, studies on actual pancreatic tissues are limited. Untargeted metabolomics analysis was conducted on 54 pairs of tumor and matched normal tissues. Taurine levels were validated via immunohistochemistry (IHC) on separate PDAC and normal tissues. Bioinformatics analysis of transcriptomics and proteomics data evaluated genes associated with taurine metabolism. Identified taurine-associated gene was validated through gene modulation. Clinical implications were evaluated using patient data. Metabolomics analysis showed a 2.51-fold increase in taurine in PDAC compared to normal tissues (n=54). IHC confirmed this in independent samples (n=99 PDAC, 19 normal). Bioinformatics identified 2-aminoethanethiol dioxygenase (ADO) as a key gene modulating taurine metabolism. IHC on a tissue microarray (39 PDAC, 10 normal) confirmed elevated ADO in PDAC. The ADOTaurine axis correlated with PDAC recurrence and disease-free survival. ADO knockdown reduced cancer cell proliferation and tumor growth in a mouse xenograft model. The MEK-related signaling pathway is suggested to be modulated by ADO-Taurine metabolism. Our multi-omics investigation revealed elevated taurine synthesis mediated by ADO upregulation in PDAC. The ADOTaurine axis may serve as a biomarker for PDAC prognosis and a therapeutic target.PMID:39637922 | DOI:10.4062/biomolther.2024.086

J Hazard Mater. 2024 Nov 27;484:136640. doi: 10.1016/j.jhazmat.2024.136640. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are widely distributed in the aquatic environment. While increasing studies have investigated the effects of specific PFAS exposure on microalgae, the impact of environmentally relevant PFAS concentrations, particularly during extreme weather events like heatwaves, remains unclear. For Microcystis aeruginosa, a cyanobacteria causing harmful algal blooms, PFAS exposure promoted growth and photosynthesis by accelerating the TCA cycle, intensifying carbon/nitrogen and nucleotide metabolism, and enhancing antioxidant expression. Moreover, although heatwave exposure alone adversely affected algal growth, co-exposure to PFAS and heatwaves paradoxically enhanced algal growth. This co-exposure also enhanced the expression of photosynthetic pigments and metabolites involved in alanine, aspartate and glutamate metabolism, as well as arginine and proline metabolism (compared to PFAS exposure alone). Nevertheless, co-exposure intensified oxidative stress, leading to differential expression of antioxidants, which may consequently affect the synthesis of membrane lipids. In addition, PFAS adsorption and uptake are primarily influenced by the varying strengths of PFAS molecules in binding with proteins and notably boosted by heatwaves. This study highlights the role of diverse PFAS in microalgae blooms and the influence of heatwave events on pollutant responses, providing scientific foundations for aquatic ecosystem protection against climate and pollution challenges.PMID:39637790 | DOI:10.1016/j.jhazmat.2024.136640