Glycerophospholipid Metabolism Research Articles

Ginseng-derived GABAFG ameliorates type 2 diabetes mellitus by modulating autophagy-lysosome pathway and gut microbiota.

Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic metabolic disease caused by insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of Panax ginseng C.A. Meyer) can be used to treat T2DM, the underlying mechanism is unclear. To assess the role and mechanism of, γ-aminobutyric acid-fructosyl-glucose (GABAFG), a maillard reaction product of ginseng, in T2DM treatment. The metabolism of GABAFG in serum and tissues was analyzed via ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UHPLC-QE-MS). The molecular mechanisms of GABAFG in pancreatic β-cells (in vivo and in vitro) were investigated via Western blotting, qPCR and immunofluorescence. In addition, the results were validated via high-throughput sequencing and serum metabolomics. GABAFG alleviated the elevation of blood glucose and blood lipids in HFD/STZ-induced T2DM mice. Also, GABAFG reduced the insulin resistance-associated IRS-1 signaling axis in pancreatic β-cells in vitro. Mechanistically, GABAFG targeted the nuclear translocation of TFEB inhibited apoptosis of pancreatic β-cells by enhancing autophagolysosome function. In addition, GABAFG remodeled the gut microbiota. Specifically, GABAFG increased Akkermansia, decreased Romboutsia abundance, and decreased serum glycerophospholipid metabolism, thus alleviating T2DM-induced dyslipidemia. This is the first study to assess the pharmacological effects of ginseng-derived GABAFG in T2DM. Therefore, this study provides a new theoretical basis for understanding ginseng effect in metabolic diseases.

Carbendazim led to neurological abnormalities by interfering metabolic profiles in zebrafish brain after short-term exposure

Carbendazim is an agricultural fungicide and a widely present ecotoxic pollutant, but its damaging effects on the nervous system are not fully understood. Here, we assessed effects of short-term exposure to carbendazim on zebrafish brains. It has been revealed firstly that carbendazim can accumulate in the brain after a 7-day exposure, with the maximum concentration of 68.22 ± 9.84 μg/kg, which caused tissue vacuolization and neuronal damage, then led to a decline in motor behavioral abilities, especially a significant reduction in the distance moved. These changes may be attributed to metabolism abnormalities. Based on metabolomics and lipidomics, substantial alterations were observed in 264 lipids and 135 metabolites, with notable enrichment in 5 metabolic pathways, including glycerophospholipid metabolism, glycerolipid metabolism, and sphingolipid metabolism. To investigate system-level variations, weighted correlation network analysis was utilized to screen for 4 biomarkers strongly associated with carbendazim exposure: citric acid, guanosine-5′-monophosphate, sphingosine, and monoacylglycerol. The alterations of these markers confirmed damages of carbendazim to zebrafish nervous system, further elucidating that metabolic disorders caused by carbendazim in brains led to tissue damage and subsequent changes in motor behavior. This study provides scientific evidence for neurotoxicities of carbendazim and offers new insights into ecological risks.

Complexation of starch and konjac glucomannan during screw extrusion exhibits obesity-reducing effects by modulating the intestinal microbiome and its metabolites.

Dietary interventions have been shown to improve gut health by altering the gut flora, preventing obesity, and mitigating inflammatory disorders. This study investigated the benefits of a rice starch-konjac glucomannan (ERS-KGM) complex, produced via screw extrusion, for gut health and obesity prevention. Analyzed through in vitro starch digestion, scanning electron microscopy, and structural analysis, the ERS-KGM complex exhibited a notable increase in resistant starch content due to its well-ordered structure. When administered to mice on a high-fat diet for 8 weeks, the ERS-KGM complex significantly reduced body weight, white adipose tissue mass, adipocyte size, and food intake while increasing water consumption. It also improved glucose metabolism, insulin sensitivity, and lipid profiles by lowering serum triglycerides and total glycerol content. Enhanced metabolic biomarkers and enzyme activities were observed, specifically involving glycerophospholipid metabolism. It decreased the activities of aldehyde dehydrogenase, lactate dehydrogenase, and amino acid transaminase while increasing antioxidant enzymes like glutathione peroxidase and superoxide dismutase. Additionally, it elevated glycogen and positively altered gut microbiota by enriching Firmicutes, Desulfobacterota, and Bifidobacterium. This change enhanced the ability to degrade specific compounds and elevated the concentrations of short-chain fatty acids in feces. These findings suggest that the ERS-KGM complex could serve as a dietary supplement for obesity prevention.

Network pharmacology and metabolomics elucidate the underlying effects and mechanisms of maackiain against endometrial cancer

Endometrial carcinoma (EC), a prevalent gynecological cancer, is characterized by rising incidence and mortality rates, highlighting the need for novel treatments to improve patient outcomes. Maackiain (MA) is a natural compound isolated from common herbal medicines, that has been reported to have MA's anti-cancer effects. However, the underlying roles and mechanisms concerning EC remain unclear. This study focused on deeply exploring the potential roles and mechanisms of MA against EC by network pharmacology, experimentally validated, metabolomics, and molecular docking. A total of 86 potential targets of MA against EC were identified by network pharmacology. In vitro experiments further confirmed network pharmacology' predictions. In addition to suppressing EC cell proliferation, MA also paused the cell cycle at the G2/M phase in a dose-dependent manner. This effect is accompanied by increased p21 and phospho-p53 expression, as well as reduced expression of CDK1 and CCNB1. Furthermore, cell metabolomics analysis revealed that 285 metabolites were changed before and after MA administration, which majorly affects glycerophospholipid metabolism, nucleotide metabolism, choline metabolism in cancer, and purine metabolism. Combination network pharmacology, metabolomics, and molecular docking, PLA2G10, PDE4D, and PDE5A were found to be potential targets for therapeutic intervention. These findings underline that MA has anti-EC potential by modulating multiple targets including PLA2G10, PDE4D, and PDE5A, inhibiting EC cell proliferation, inducing G2/M phase arrest, and causing metabolic shifts. This study provides theoretical support for advanced experimental research on its clinical applications.

Pharmacokinetic and Metabolomic Studies with BBT-059 in Nonhuman Primates Exposed to Total-Body Gamma Radiation.

BBT-059 is a long-acting PEGylated interleukin-11 analog that has been shown to have hematopoiesis-promoting and anti-apoptotic attributes, and is being studied as a radiation countermeasure for the hematopoietic acute radiation syndrome (H-ARS). This potential countermeasure has been demonstrated to enhance survival in irradiated mice. To investigate the toxicity and safety profile of this agent, 14 nonhuman primates (NHPs, rhesus macaques) were administered two different doses of BBT-059 subcutaneously 24 h after 4 Gy total-body irradiation and were monitored for the next 60 days postirradiation. Blood samples were investigated for the pharmacokinetics and pharmacodynamics of this agent and its effects on complete blood counts, cytokines, vital signs, and for metabolomic studies. No adverse effects were observed in either treatment group. Radiation-induced metabolomic dysregulation was observed in both treatment groups, and BBT-059 afforded some short-term radiomitigation. A few pathways were commonly dysregulated by radiation exposure including the steroid hormone biosynthesis pathway, fatty acid activation, and glycerophospholipid metabolism. Notably, radiation-induced dysregulation to the linoleate metabolism pathway was significantly mitigated by either dose of BBT-059. In brief, this study suggests that BBT-059 has a good safety profile in irradiated NHPs and that its development as a medical countermeasure for U.S. Food and Drug Administration approval for human use should be continued.

Serum lipid profiling reveals characteristic lipid signatures associated with stroke in patients with leukoaraiosis

Many lipid biomarkers of stroke have been identified, but the lipid metabolism in elderly patients with leukoaraiosis remains poorly understood. This study aims to explore lipid metabolic processes in stroke among leukoaraiosis patients, which could provide valuable insights for guiding future antithrombotic therapy. In a cohort of 215 individuals undergoing MRI, 13 stroke patients were matched with controls, and 48 stroke patients with leukoaraiosis were matched with 40 leukoaraiosis patients. Serum lipidomics was profiled using UPLC-TOF, and OPLS-DA was applied for metabolite identification. Partial Least Squares Path Model (PLS-PM) assessed pathway weights of novel metabolites in stroke risk, while linear regression explored correlations with clinical outcomes. Lipid profiling identified 168 distinct compounds. From these, 25 lipid molecules were associated with glycerolipid, glycerophospholipid, and sphingolipid metabolism. PLS-PM identified 12 key metabolites, including DG 36:4 (OR = 6.40) as a significant risk factor. Metabolites such as PE 38:5 and FA 16:1;O showed significant correlations with stroke in leukoaraiosis, particularly when the Fazekas score was ≥ 4. Twelve metabolites were identified as key factors in stroke incidence among leukoaraiosis patients. Lipid disturbances in glycerolipids and glycerophospholipids provide valuable insights for further studies on the progression from leukoaraiosis to stroke.

Effects of Saprolegnia parasitica on pathological damage and metabolism of Epithelioma papulosum cyprini cell.

Saprolegniasis is a common fungal disease in aquaculture. It will form white flocculent hyphae on the skin of fish, and the hyphae may grow inward and penetrate into muscle tissue, which will reduce the immunity of the body and eventually lead to death. However, there are still some gaps in the mechanism of the fish body surface against the invasion of Saprolegnia. This study explored the defense mechanism of Epithelioma papulosum cyprini cell (EPC) in the process of Saprolegnia parasitica infection from the perspective of pathogenic bacteria and host cells, so as to provide a theoretical basis for further exploring the mechanism of host resistance to S. parasitica invasion. The EPC cell was used as the research object. The EPC cells were treated with 1×106 CFU/mL of S. parasitica for 0, 6, 12, 24, 48 and 72 h. Cell viability and cell membrane damage were detected, and the non-specific immune enzyme activity in the cells was detected. Based on the above research, the apoptosis genes and antioxidant genes in the cells were detected to analyze the effect of S. parasitica on the metabolism of the EPC cells. The results showed that with the prolongation of the co-culture time of S. parasitica and cells, the cell viability gradually decreased and the cell membrane integrity was destroyed, but at the same time, the activity of non-specific immune enzymes increased to resist the infection of S. parasitica. In addition, the detection of EPC apoptosis gene casp3a and CTSD showed that the relative content of casp3a gene increased significantly at 24 h and reached the maximum value of the culture time (P<0.05). The content of CTSD gene increased significantly at 12 h and reached the maximum value (P<0.05). The results of antioxidant immune genes serpinh1a and gpx1a were opposite to the structure of apoptotic genes. The content of serpinh1a and gpx1a genes decreased significantly at 12 h (P<0.05), but with the prolongation of culture time, the content increased significantly at 24 h and 48 h (P<0.05). After stimulation of EPC cells by S. parasitica, the differential metabolites were mainly concentrated in Lipids, Compounds with biological roles and Phytochemical compounds. The KEGG pathway mainly focused on ABC transporters, Glycerophospholipid metabolism, Cysteine and methionine metabolism, Glycine, serine and threonine metabolism, Purine metabolism. In general, S. parasitica can affect cell activity, destroy the cell membrane of EPC cells, and cause apoptosis. However, EPC cells can also resist the invasion of S. parasitica by regulating their own non-specific immunity and their own metabolites, thereby protecting the body from the infection of S. parasitica.

ENPP2 promotes progression and lipid accumulation via AMPK/SREBP1/FAS pathway in chronic lymphocytic leukemia

BackgroundDisorders of lipid metabolism are critical factors in the progression of chronic lymphocytic leukemia (CLL). However, the characteristics of lipid metabolism and related regulatory mechanisms of CLL remain unclear.MethodsHence, we identified altered metabolites and aberrant lipid metabolism pathways in patients with CLL by ultra-high-performance liquid chromatography-mass spectrometry-based non-targeted lipidomics. A combination of transcriptomics and lipidomics was used to mine relevant target molecule and downstream signaling pathway. In vitro cellular assays, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, fluorescent staining, RNA sequencing, and coimmunoprecipitation were used to monitor the molecular levels as well as to explore the underlying mechanisms.ResultsSignificant differences in the content of 52 lipid species were identified in CLL samples and healthy controls. Functional analysis revealed that alterations in glycerolipid metabolism, glycerophospholipid metabolism, sphingolipid metabolism, and metabolic pathways had the greatest impact on CLL. On the basis of the area under the curve value, a combination of three metabolites (phosphatidylcholine O-24:2_18:2, phosphatidylcholine O-35:3, and lysophosphatidylcholine 34:3) potentially served as a biomarker for the diagnosis of CLL. Furthermore, utilizing integrated lipidomic, transcriptomic, and molecular studies, we reveal that ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) plays a crucial role in regulating oncogenic lipogenesis. ENPP2 expression was significantly elevated in patients with CLL compared with normal cells and was validated in an independent cohort. Moreover, ENPP2 knockdown and targeted inhibitor PF-8380 treatment exerted an antitumor effect by regulating cell viability, proliferation, apoptosis, cell cycle, and enhanced the drug sensitivity to ibrutinib. Mechanistically, ENPP2 inhibited AMP-activated protein kinase (AMPK) phosphorylation and promoted lipogenesis through the sterol regulatory element-binding transcription factor 1 (SREBP-1)/fatty acid synthase (FAS) signaling pathway to promote lipogenesis.ConclusionsTaken together, our findings unravel the lipid metabolism characteristics of CLL. Moreover, we demonstrate a previously unidentified role and mechanism of ENPP2 in regulation of lipid metabolism, providing a novel therapeutic target for CLL treatment.

Lc—ms-based untargeted metabolomics reveals potential mechanisms of histologic chronic inflammation promoting prostate hyperplasia

Background Chronic prostatitis may be a risk factor for developing proliferative changes in the prostate, although the underlying mechanisms are not entirely comprehended. Materials and methods Fifty individual prostate tissues were examined in this study, consisting of 25 patients diagnosed with prostatic hyperplasia combined with histologic chronic inflammation and 25 patients diagnosed with prostatic hyperplasia alone. We employed UPLC-Q-TOF-MS-based untargeted metabolomics using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to identify differential metabolites that can reveal the mechanisms that underlie the promotion of prostate hyperplasia by histologic chronic inflammation. Selected differential endogenous metabolites were analyzed using bioinformatics and subjected to metabolic pathway studies. Results Nineteen differential metabolites, consisting of nine up-regulated and ten down-regulated, were identified between the two groups of patients. These groups included individuals with combined histologic chronic inflammation and those with prostatic hyperplasia alone. Glycerolipids, glycerophospholipids, and sphingolipids were primarily the components present. Metabolic pathway enrichment was conducted on the identified differentially expressed metabolites. Topological pathway analysis revealed the differential metabolites’ predominant involvement in sphingolipid, ether lipid, and glycerophospholipid metabolism. The metabolites involved in sphingolipid metabolism were Sphingosine, Cer (d18:1/24:1), and Phytosphingosine. The metabolites involved in ether lipid metabolism were Glycerophosphocholine and LysoPC (O-18:0/0:0). The metabolites involved in glycerophospholipid metabolism were LysoPC (P-18:0/0:0) and Glycerophosphocholine. with Impact &gt; 0. 1 and FDR &lt; 0. 05, the most important metabolic pathway was sphingolipid metabolism. Conclusions In conclusion, our findings suggest that patients with prostate hyperplasia and combined histologic chronic inflammation possess distinctive metabolic profiles. These differential metabolites appear to play a significant role in the pathogenesis of histologic chronic inflammation-induced prostate hyperplasia, primarily through the regulation of sphingolipids and glycerophospholipids metabolic pathways. The mechanism by which histologic chronic inflammation promotes prostate hyperplasia was elucidated through the analysis of small molecule metabolites. These findings support the notion that chronic prostatitis may contribute to an increased risk of prostate hyperplasia.

Analysis of Immunosuppression and Antioxidant Damage in Diploid and Triploid Crucian Carp (Carassius auratus) Induced by Saline-Alkaline Environmental Stress: From Metabolomic Insight.

Objectives: The salinization of the water environment worldwide is increasing, which has brought great challenges to the sustainability of fish farming of aquatic animals. Methods: Three NaHCO3 concentration groups (0 mmol/L, 20 mmol/L, and 60 mmol/L) were set up in this study to investigate growth and metabolic differences between diploid and triploid crucian carp under saline-alkaline stresses. Purpose: This study utilized UPLC-QTOF/MS metabolomics to analyze significant metabolites and metabolic pathways in the serum of diploid and triploid crucian carp, exposing them to different NaHCO3 concentrations in saline-alkaline habitats, elucidating the mechanism of their metabolic differences. Results: Results revealed that in the CA20 group, diploid and triploid crucian carp shared 69 differential metabolites, primarily enriched in pathways such as sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. In the CA60 group, 46 differentially metabolites (DMs) were identified, mainly enriched in pathways such as linoleic acid metabolism, unsaturated fatty acid biosynthesis and sphingolipid metabolism. Conclusions: The analysis indicated that under different carbonate-saline-alkaline concentrations, diploid and triploid crucian carp primarily enriched in metabolic pathways such as glycerophospholipid metabolism, sphingolipid metabolism, and unsaturated fatty acid biosynthesis. With increasing carbonate-alkaline concentrations, hemolytic phospholipids associated with cell apoptosis were significantly upregulated and sphingolipid metabolism related to inflammation was more significantly enriched in triploid crucian carp, indicating that triploid crucian carp exhibited significant sensitivity to high carbonate-saline-alkaline stress and poorer carbonate-saline-alkaline tolerance. The results of this study provided a scientific theoretical basis for the later cultivation and aquaculture research of saline-alkaline-tolerant fish species.

Foliar Application of Zinc Oxide Nanoparticles Alleviates Phenanthrene and Cadmium-Induced Phytotoxicity in Lettuce: Regulation of Plant-Rhizosphere-Microbial Long Distance.

Foliar application of beneficial nanoparticles exhibits potential in mitigating combined stresses from heavy metals and polycyclic aromatic hydrocarbons (PAHs) in crops, necessitating a comprehensive understanding of plant-rhizosphere-microbial processes to promote sustainable nanotechnology in agriculture. Herein, we investigated the mitigating mechanisms of foliar application of zinc oxide nanoparticles (nZnO) on lettuce growth under phenanthrene (Phe) and cadmium (Cd) costress. Compared to Phe + Cd treatment, low (L-nZnO) and high (H-nZnO) concentration of nZnO increased fresh biomass (27.2% and 8.42%) and root length (20.4% and 39.6%) and decreased MDA (35.0% and 40.0%) and H2O2 (29.0% and 15.6%) levels. L-nZnO and H-nZnO decreased Cd in roots (26.8% and 41.8%) and enhanced Zn in roots (19.9% and 107%), stems (221% and 2510%), and leaves (233% and 1500%), suggesting the long-distance migration of Zn from leaves to roots and subsequently regulating the metabolic pathways and microbial communities. Metabolomics revealed that nZnO modulated leaf glycerophospholipid metabolism and amino acid pathways and promoted rhizosphere soil carbon and phosphorus metabolism. Additionally, nZnO enriched the plant-growth-promoting, extreme, and stress-resistant bacteria in roots and leaves and heavy-metal-resistant and PAH-degrading bacteria in rhizosphere soil. These findings underscore the promising nanostrategy of nZnO to benefit plant growth in soil cocontaminated with heavy metals and PAHs.

Serum metabolic alterations in chickens upon infectious bursal disease virus infection

BackgroundInfectious bursal disease virus (IBDV) is a highly contagious immunosuppressive virus of chickens. Chickens acquire infection by the oral route under natural conditions. Although the histological and pathological changes after IBDV infection are well described, the alterations in serum metabolome have not been reported. In this study, SPF chickens were infected with attenuated IBDV (atIBDV) strain LM and very virulent IBDV (vvIBDV) strain LX, respectively. On the seventh day after oral infection, serum samples of experimental chickens were identified using ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS). The serum metabolic profiles were analyzed by multivariate statistical methods. KEGG enrichment analysis was performed to evaluate the dysregulated biological pathways.ResultsWe identified 368 significantly altered metabolites in response to both atIBDV and vvIBDV infection. The metabolic disorder of amino acid and lipid was associated with IBDV infection, especially tryptophan, glycerophospholipid, lysine, and tyrosine metabolism. The differential metabolites enriched in the four metabolic pathways were PC(20:4(5Z,8Z,11Z,14Z)/18:0), PE(16:0/18:2(9Z,12Z)), PE(16:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PE(18:0/20:4(5Z,8Z,11Z,14Z)), PE(18:0/20:4(8Z,11Z,14Z,17Z)), PE(18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PE(20:3(8Z,11Z,14Z)/16:0), PE(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:0), PE-NMe(20:5(5Z,8Z,11Z,14Z,17Z)/18:0), PS(20:3(5Z,8Z,11Z)/18:2(9Z,12Z)), 2-aminobenzoic acid, 4-(2-aminophenyl)-2,4-dioxobutanoic acid, N-acetylserotonin, 5-hydroxyindoleacetate, indole-3-acetaldehyde, indole-3-acetate, p-coumaric acid, L-tyrosine, homovanillin, and S-glutaryldihydrolipoamide.ConclusionThe atIBDV and vvIBDV infection causes metabolic changes in chicken serum. The differential metabolites and dysregulated metabolic pathways reflect the host response to the IBDV infection.

Wolfberry Honey and Its Extract Alleviate Dextran Sodium Sulfate-Induced Ulcerative Colitis by Improving Intestinal Barrier Function and Reducing Oxidative Stress and Inflammation.

Inflammatory bowel disease (IBD) is a chronic condition characterized by gut inflammation causing persistent diarrhea and abdominal pain. Despite the nutritional benefits of wolfberry honey (from Lycium barbarum L.), its potential to alleviate IBD remains underexplored. This study evaluated the protective effects of wolfberry honey and its extract (wolfberry honey extract [WHE]) against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) using in vivo and in vitro models. Mice pretreated with wolfberry honey showed significant symptom improvement in DSS-induced UC, linked to reduced expression of proinflammatory markers (Il-1β, Il-6, Tnf-α, and Mcp-1) and increased antioxidant genes (Nrf2, Sod2). Increased Occludin levels indicated improved intestinal barrier function. In vitro, WHE protected DSS-treated Caco-2 cells by lowering reactive oxygen species (ROS), stabilizing mitochondrial membrane potential, and inhibiting TLR4/NF-κB signaling. It enhanced the expression of antioxidant genes and tight junction proteins (ZO-1, Occludin, and Claudin-1). Metabolomic analysis revealed that WHE modulated glycerophospholipid metabolism, increasing phosphatidylcholine and choline levels and decreasing lysophosphatidylcholine levels. These results highlight the potential of wolfberry honey and its extract as nutraceuticals for managing UC through their effects on inflammation, oxidative stress, and intestinal barrier function. Further research is warranted to elucidate their mechanisms of action and assess their long-term therapeutic benefits in IBD management.

From Tea to Functional Foods: Exploring Caryopteris mongolica Bunge for Anti-Rheumatoid Arthritis and Unraveling Its Potential Mechanisms.

Caryopteris mongolica Bunge (CM) shows promising potential for managing rheumatoid arthritis (RA) and digestive disorders, attributed to its rich content of bioactive compounds such as polyphenols and flavonoids. Despite its common use in herbal tea, the specific mechanisms underlying CM's anti-inflammatory and joint-protective effects remain unclear, limiting its development as a functional food. This study investigated the effects of aqueous CM extract on RA in collagen-induced arthritis (CIA) rats and explored the underlying mechanisms. Forty-eight female Sprague-Dawley rats were randomly assigned to six groups (n = 8): normal control, CIA model, methotrexate (MTX), and CM high-, middle-, and low-dose groups. Anti-inflammatory and joint-protective effects were evaluated using biochemical and histological analyses. To elucidate the mechanisms, we applied metabolomics, network pharmacology, and transcriptomics approaches. The results demonstrated that CM extract effectively suppressed synovial inflammation in CIA rats, reducing joint degradation. CM's anti-inflammatory effects were mediated through the TNF signaling pathway, modulating glycerophospholipid and amino acid metabolism, including reduced levels of tryptophan, LysoPC, and asparagine. Molecular docking identified scutellarin and apigenin as key bioactive compounds. Additionally, immunofluorescence analysis revealed CM's therapeutic effects via TNF signaling inhibition and suppression of M1 macrophage polarization. These findings highlight the therapeutic potential of CM for RA and support its development as a functional food or pharmaceutical product.

Weizmannia coagulans BC99 alleviates hyperuricemia and oxidative stress via DAF-16/SKN-1 activation in Caenorhabditis elegan.

Hyperuricemia (HUA) refers to the presence of excess uric acid (UA) in the blood, which increases the risk of chronic kidney disease and gout. Probiotics have the potential to alleviate HUA. This study established a hyperuricemia model using Caenorhabditis elegans (C. elegans), and studied the anti-hyperuricemia activity and potential mechanisms of Weizmannella coagulans BC99 (W. coagulans) at different concentrations (107 CFU/mL BC99, 108 CFU/mL BC99). Subsequently, we utilized UPLC-Q-TOF/MS to investigate the impact of BC99 on endogenous metabolites in C. elegans and identified pathways and biomarkers through differential metabolomics analysis. The results of this study showed that BC99 treatment significantly reduced the expression of P151.2 and T22F3.3 (p < 0.05), reduced the levels of UA and xanthine oxidase (XOD) in nematodes (p < 0.05), while extending their lifespan and movement ability (p < 0.05). Mechanistically, BC99 activates the transcription factors DAF-16 and SKN-1, thereby inducing the expression of stress response genes, enhancing the activity of antioxidant enzymes and tolerance to heat stress in the body, and reducing the production of ROS (p < 0.001). This effect was most significant in the H-BC99 group. Furthermore, non-targeted metabolomics indicated that BC99 predominantly regulated pathways associated with amino acid metabolism (Carnosine), glycerophospholipid metabolism, and purine metabolism. These results underscore BC99 as an effective and economical adjunct therapeutic agent for hyperuricemia, providing a scientific basis for further development and application.

Metabolomics profiles of the liquid co-culture of Sanghuangporus vaninii and Pleurotus sapidus

IntroductionFungal secondary metabolites (SMs) have broad application prospects in the food and medicine industries. Co-culturing strategies that simulate natural symbiotic relationships among microorganisms are used to discover and enhance the production of new SMs. We aimed to use the abundant resources of large edible and medicinal fungi to enhance the yield of desired metabolites through co-culture and potentially produce metabolites that cannot be generated in pure cultures.MethodsWe assessed the biomass and intracellular polysaccharide (IPS) content of liquid co-cultures of Sanghuangporus vaninii and Pleurotus sapidus. Subsequently, the effect of the liquid co-culture on fungal intracellular metabolites was studied using UPLC-QTOF.ResultsCo-culturing of S. vaninii with P. sapidus resulted in significantly increased biomass and IPS content; however, P. sapidus had a significant inhibitory effect on the growth of S. vaninii. Metabolomic data further indicated that amino acid, nucleotide, and glycerophospholipid metabolisms were the primary metabolic pathways affected by symbiosis.DiscussionThis study provides insights into fungal interactions and cellular metabolic mechanisms, contributing to the understanding and enhancement of the fungal fermentation potential.

Multi-Omics Analysis of the Molecular Mechanisms by Which Extract of Artemisia selengensis Turcz. Ameliorates DBP-Induced Liver Injury.

Artemisia selengensis Turcz. is a perennial herb belonging to the genus Artemisia in the family Asteraceae. Known for its nutrient richness, distinct flavor, and medicinal properties, Artemisia selengensis Turcz. has garnered attention. However, its efficacy, particularly in alleviating hepatic injury, remains underexplored. This study aims to assess the therapeutic potential of the 50% ethanol extract of Artemisia selengensis Turcz. (ASTE) in a mouse model of dibutyl phthalate (DBP)-induced liver injury. Through multi-omics analysis, including transcriptomics, metabolomics, and intestinal flora examination, we explored the pathways and key targets of ASTE in treating liver injury. Network pharmacology further identified the crucial components of ASTE for liver injury treatment. Our findings indicate that ASTE affects intestinal flora such as Adlercreutzia through flavonoids, particularly naringin and epicatechin. Additionally, key genes in the PPAR pathway, such as fatty acid-binding protein 3 (Fabp3), fatty acid-binding protein 5 (Fabp5), 3-hydroxyacyl-CoA dehydrogenase (Ehhadh), and phospholipid transfer protein (Pltp), influence glycerophospholipid metabolism, contributing to liver injury amelioration. This study sheds light on the molecular mechanisms underlying ASTE's hepatoprotective effects, laying the groundwork for its potential application as a functional food.

Lipidomics in Obesity: Unveiling Metabolic Pathways Contributing to Hyperlipidemia

Obesity, a global public health challenge, is intricately linked to hyperlipidemia, which significantly increases the risk of metabolic syndrome, cardiovascular diseases, and type 2 diabetes. Lipidomics, the comprehensive study of lipid profiles within biological systems, has emerged as a powerful tool for unraveling the complex lipid metabolic alterations that occur in obesity. This review provides a detailed analysis of lipidomics and its application in understanding the dysregulated metabolic pathways contributing to hyperlipidemia in obesity. We examine key lipid species, including fatty acids, triglycerides, phospholipids, sphingolipids, and cholesterol, and their roles in adipose tissue dynamics, insulin resistance, and inflammation. Furthermore, the review highlights the involvement of critical lipid metabolic pathways such as de novo lipogenesis, fatty acid oxidation, glycerophospholipid metabolism, and sphingolipid signaling in obesity-induced hyperlipidemia. Emerging lipidomic technologies and their potential to uncover novel biomarkers and therapeutic targets for managing dyslipidemia in obese individuals are also discussed. By integrating lipidomics into obesity research, we can gain a more nuanced understanding of the lipid-related molecular mechanisms driving hyperlipidemia and develop more targeted, personalized therapeutic strategies. Keywords: Lipidomics, Obesity, Hyperlipidemia, Metabolic Pathways, Fatty Acid Metabolism, De Novo Lipogenesis, Sphingolipids, Biomarkers, Cardiovascular Risk, Dyslipidemia

The difference in salinity tolerance between cultured and wild sea cucumber Apostichopus japonicus Selenka based on survival, enzyme activity and transcriptome analyses

Salinity is a critical environmental factor affecting the growth, survival, distribution, and physiological processes of the sea cucumber, Apostichopus japonicus (Selenka). In this study, we examined the survival rates, enzymatic activities, and transcriptomes of one cultured and two wild populations of the sea cucumber, A. japonicus Selenka to compare their tolerance across a range of salinities. Significant differences in survival rates were observed among the three populations when exposed to salinity levels of 45, 40, 23, 20, and 17 psu. As salinity decreased, the activities of catalase, Na+-K+-ATPase, amylase and superoxide dismutase in cultured sea cucumbers peaked at 23 psu, and declined at 20 psu. In contrast, the activities of these enzymes in wild sea cucumbers decreased at 23 psu. At 40 psu, the four enzymatic activities significantly decreased in cultured sea cucumbers but continued to increase significantly in wild populations (P &lt; 0.05). Transcriptomic analysis based on Gene Ontology (GO) function revealed the terms “cellular process,” “membrane” and “binding” were most enriched in the biological process, cellular component, and molecular function categories, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified “Glycerophospholipid metabolism” and “Starch and sucrose metabolism” among the top 10 most enriched pathways. The findings of this study provide new insights into the salinity tolerance adaptation of cultured sea cucumbers.

Astragaloside IV alleviates diabetic nephropathy by modulating the kidney-gut axis AMPK/PI3K/AKT pathway

Diabetic nephropathy (DN) is a severe complication of diabetes characterized by altered metabolic pathways. Astragaloside IV, a bioactive compound derived from Astragalus membranaceus, has shown potential therapeutic effects in various diseases. This study aims to investigate the protective effects of Astragaloside IV on DN through histomorphological, metabolomic, molecular biological, and gut flora-renal axis approaches. Serum metabolomics analyses were conducted to identify changes in metabolic pathways, focusing on glycerophospholipid metabolism and bile acid metabolism. Additionally, the activation of the AMPK/PI3K/AKT signaling pathway in kidney were examined. The impact of Astragaloside IV on the gut flora-renal axis was assessed by analyzing the relative abundance of specific gut microbiota and their correlations with metabolic parameters. Serum metabolomics analyses revealed significant alterations in glycerophospholipid and bile acid metabolism pathways. Astragaloside IV treatment activated the AMPK/PI3K/AKT signaling pathway, regulate glycolipid metabolism and mitochondrial damage to improve kidney injury. Moreover, Astragaloside IV modulated the relative abundance of gut microbiota, notably increasing Muribaculaceae and Alloprevotella. The relative abundance of Bacteroidota was positively correlated with high-density lipoprotein (HDL) levels and negatively correlated with fasting blood glucose (FBG) and low-density lipoprotein (LDL) levels. Astragaloside IV exerts protective effects against DN by improving the intestinal microenvironment and activating the AMPK/PI3K/AKT signaling pathway in kidney. These findings highlight the therapeutic potential of Astragaloside IV and suggest the efficacy of gut-liver axis mediated therapies for the treatment of DN.