Elucidating ascorbate and aldarate metabolism pathway characteristics via integration of untargeted metabolomics and transcriptomics of the kidney of high-fat diet-fed obese mice

PLoS ONE, Год журнала: 2024, Номер 19(4), С. e0300705 - e0300705

Опубликована: Апрель 11, 2024

Obesity is a major independent risk factor for chronic kidney disease and can activate renal oxidative stress injury. Ascorbate aldarate metabolism an important carbohydrate metabolic pathway that protects cells from damage. However the effect of on this still unclear. Therefore, primary objective study was to investigate ascorbate in kidneys high-fat diet-fed obese mice determine effects stress. Male C57BL/6J were fed diet 12 weeks induce obesity. Subsequently, non-targeted metabolomics profiling used identify metabolites tissues mice, followed by RNA sequencing using transcriptomic methods. The integrated analysis transcriptomics revealed alterations these mice. diet-induced obesity resulted notable changes, including thinning glomerular basement membrane, podocyte morphology, increase Metabolomics 649 positive-ion mode, 470 negative-ion mode. Additionally, 659 differentially expressed genes (DEGs) identified which 34 upregulated 625 downregulated. Integrated analyses two DEGs 13 differential pathway. expression levels ugt1a9 ugt2b1 downregulated, level tissue reduced. Thus, injury induced affects regulation emerged as potential marker predicting damage due

Язык: Английский

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Study on the material basis and action mechanisms of sophora davidii (Franch.) skeels flower extract in the treatment of non-small cell lung cancer

Journal of Ethnopharmacology, Год журнала: 2023, Номер 317, С. 116815 - 116815

Опубликована: Июль 1, 2023

Язык: Английский

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Comparing the effects of empagliflozin and liraglutide on lipid metabolism and intestinal microflora in diabetic mice

PeerJ, Год журнала: 2024, Номер 12, С. e17055 - e17055

Опубликована: Март 15, 2024

Recent studies have shown that the imbalance of intestinal flora is related to occurrence and progression diabetic nephropathy (DN) can affect lipid metabolism. Sodium-dependent glucose transporters 2 (SGLT2) inhibitor glucagon-like peptide-1 (GLP-1) receptor agonist are commonly used hypoglycemic drugs excellent renal safety. The purpose this study was compare protective effects empagliflozin liraglutide on kidneys, metabolism, microbiota in mice. We established a mouse model type two diabetes by feeding rats high-fat diet (HFD) followed an intraperitoneal injection STZ. mice were randomly divided into groups: normal control (NC), (DM), treatment (LirT), (EmpT), combined with (Emp&LirT) groups. Blood glucose, lipids, creatinine, uric acid, as well urinary nitrogen albumin levels measured. tissues subjected HE, PAS Masson's staining. These parameters evaluate function histopathological changes Mice feces also collected for 16sRNA sequencing analyze composition flora. All indexes significantly improved after drugs. With respect both decreased serum triglyceride mice, but effect reducing cholesterol better than empagliflozin. However, had reduction low-density lipoproteins (LDL). different At phylum level, reduced ratio Firmicutes Bacteroidota, no seen liraglutide. genus them number Helicobacter increased Lactobacillus. Empagliflozin abundance Muribaculaceae, Muribaculum, Olsenella, Odoribacter, while Ruminococcus. Liraglutide able improve diabetes-related injury. ability reduce LDL compared In addition, their intestine bacterial different.

Язык: Английский

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Network pharmacology, molecular docking, and experimental verification reveal the mechanism of Yi-Shen-Hua-Shi granules treating acute kidney injury

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119320 - 119320

Опубликована: Янв. 1, 2025

Язык: Английский

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Investigating the biological significance of the TCM principle “promoting urination to regulate bowel movements” through the influence of the intestinal microbiota and their metabolites on the renal-intestinal axis

Frontiers in Cellular and Infection Microbiology, Год журнала: 2025, Номер 14

Опубликована: Янв. 10, 2025

Treatment methods in traditional Chinese medicine (TCM) are foundational to their theoretical, methodological, formulaic, and pharmacological systems, significantly contributing syndrome differentiation therapy. The principle of "promoting urination regulate bowel movements" is a common therapeutic approach TCM. core concept the dispersion drainage water dampness, regulating relieve diarrhea," yet its scientific underpinning remains unclear. Modern medical treatment for watery diarrhea primarily focuses on electrolyte replenishment, as diuretics may lead dehydration other side effects. Some reports suggest that this TCM lacks validity. Microecology, an area associated with origins TCM, closely related development, diagnosis, diarrhea. renal-intestinal axis offers molecular biological basis examining pathological mechanisms, advancing targets such "treating intestine address kidney issues" highlighting interactions within "renal-intestinal microbiota-liquid metabolism" framework, thus providing endogenous mechanism support through kidney." An increasing number studies have shown intestinal microbiota metabolites, unique mediators, involved physiological changes body. Therefore, study explores relationship between fluid metabolism from perspective aiming elucidate mechanisms underlying clarify treating via axis. This research provides new insights microbiology.

Язык: Английский

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Integrated metabolomics and mass spectrometry imaging analysis reveal the efficacy and mechanism of Huangkui capsule on type 2 diabetic nephropathy

Phytomedicine, Год журнала: 2025, Номер 138, С. 156397 - 156397

Опубликована: Янв. 16, 2025

Язык: Английский

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Causal relationship between 412 gut microbiota, 1,400 blood metabolites, and diabetic nephropathy: a randomized Mendelian study

Frontiers in Endocrinology, Год журнала: 2025, Номер 15

Опубликована: Янв. 17, 2025

The aim of this study was to investigate the causal relationship between microbiota, diabetic nephropathy, and blood metabolites through a randomized Mendelian study. In study, we used 412 microbiota as exposures, 1,400 intermediaries, nephropathy outcome. We conducted two-way randomization (MR) analysis explore followed by mediation analyses two-step MR identify potential metabolites. There is nephropathy. Specific bacteria metabolites, such Escherichia coli str. K-12 substr. MG1655, Listeria monocytogenes 10403S, g_Adlercreutzia, g_Haemophilus, g_Bacteroides, CFT073, like pyrraline, glycocholenate sulfate, alpha-ketoglutarate, tetradecadienoate (14:2), Cys-gly oxidized, methylsuccinate, various others, were identified. MG1655 positively related alpha-ketoglutarate levels, while levels Sphingomyelin (d18:1/18:1, d18:2/18:0) are negatively related. bacterial involved in fatty acid oxidation associated with kidney disease (DKD) progression, correlated sulfate phosphate linoleyl-tetraenyl-glycerol (18:2 20:4) ratio. Additionally, 10403S N-acetyl-isoputreanine X-12462. Anaerobic fermentation-related N-acetylcarnitine 5-acetylamino-6-formyluracil 5-acetamino-6-amino-3-methyluracil (X-24243). CFT073 X-16580. Interactions Bacillus species d18:1/18:1, d18:2/18:0, 2-aminophenol cholate negative when compared (14:2). g_Adlercreutzia N-delta-acetylornithine, but N-acetylglucosamine N-acetylgalactosamine. g_Haemophilus arachidoylcarnitine X-24531. results heterogeneous multi-efficacious. For first time, provides supportive evidence for bidirectional identifies specific genes disease. suggest that probiotic therapy may play significant role preventing improving quality life survival rates affected patients. Furthermore, additional

Язык: Английский

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The gut–kidney axis is regulated by astragaloside IV to inhibit cyclosporine A-induced nephrotoxicity

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 27, 2025

Introduction Chronic nephrotoxicity caused by CNIs (CICN) manifests clinically as chronic kidney disease (CKD). Astragaloside IV (AS-IV) plays a certain role in the treatment of CKD. This study aimed to verify ameliorative effects AS-IV on CICN and further explore mechanisms underlying modulation “gut–transcriptome–metabolome coexpression network” within context “gut–kidney axis” improve CICN. Methods Five groups 40 mice were studied: normal group (N, olive oil), model (M, CsA, 30 mg kg -−1 d −1 ), low-dose (CsA + AS-IV, 10 high-dose 20 valsartan Val, ). The gut microbiota, renal transcriptome, urine metabolome separately detected construct gut–transcriptome–metabolome network. target species, genes, metabolites evaluated. Results CsA led increased proteinuria deterioration function, accompanied inflammation oxidative stress, whereas improved damage. inhibited intestinal permeability disrupted microbiota structure, increasing abundance Lactobacillus reuteri , Bifidobacterium animalis Ignatzschineria indica Blautia glucerasea. Six pathways related transcription metabolism, including citrate cycle ascorbate aldarate metabolism proximal tubule bicarbonate reclamation glycolysis/gluconeogenesis, ferroptosis, drug metabolism–cytochrome P450 identified. Seven identified 6 pathways, UDP-D-galacturonic acid, 2-phenylethanol glucuronide, dehydroascorbic isopentenyl pyrophosphate, alpha-D-glucose, 3-carboxy-1-hydroxypropylthiamine diphosphate citalopram aldehyde. genes Ugt1a2, Ugt1a9, Ugt1a5, Pck1, Slc7a11, also predicted NONMMUT144584.1, MSTRG.30357.1 ENSMUST00000174821. was highly correlated with function AS-IV. validated. intestinal-derived urinary toxins tissue apoptosis, lipid accumulation, collagen deposition, mitochondrial Conclusion through six energy driven L. alderate tube are important mechanisms.

Язык: Английский

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Serum metabolic profiling of patients with diabetic kidney disease based on gas chromatography-mass spectrometry

Frontiers in Molecular Biosciences, Год журнала: 2025, Номер 12

Опубликована: Март 17, 2025

Given the increasing incidence rate of diabetic kidney disease (DKD), there is an urgent need for methods to diagnose and treat DKD in clinics. Serum samples were collected from 56 patients 32 healthy controls (HCs) at First Affiliated Hospital Ningbo University, metabolic profiles obtained through untargeted metabolomics using gas chromatography mass spectrometry. The data then analyzed principal components analysis, orthogonal partial least-squares discriminant Pearson correlation receiver operating characteristic (ROC) curve. It was found that serum significantly different those HCs. A total 68 potential differential metabolites identified involved arginine biosynthesis, ascorbate aldarate metabolism, galactose among others; a 31 also between early-stage (EDG) late-stage (LDG) patients. Additionally, 30 significant differences observed EDG, LDG, HC groups. Based on analysis abundances clinical markers (estimated glomerular filtration rate, blood urea nitrogen, creatinine, urinary albumin/creatinine ratio) area under ROC curve (AUROC) AUROC values myoinositol gluconic acid be 0.992 0.991, respectively, which can used distinguish These results indicate could possibly as biomarkers DKD.

Язык: Английский

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The gut microbiota and diabetic nephropathy: an observational study review and bidirectional Mendelian randomization study

Trials, Год журнала: 2025, Номер 26(1)

Опубликована: Март 24, 2025

Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering gut-kidney axis; however, specific cause-and-effect connections these processes remain unclear. To compare changes in GM DN patients control subjects, review of observational was performed. The examination focused on phylum, family, genus, species/genus categories. delve deeper into cause–effect relationship, instrumental variables for 211 taxa (9 phyla, 16 classes, 20 orders, 35 families, 131 genera), which were eligible mbQTL (microbial quantitative trait locus) mapping analysis, collected from Genome Wide Association Study (GWAS). A Mendelian randomization investigation then conducted to gauge their impact susceptibility using data European Bioinformatics Institute (EBI) FinnGen consortium. included 1032 451,248 controls, while consortium consisted 3283 210,463 controls. Two-sample (TSMR) utilized determine DN. primary method analysis inverse variance weighted (IVW) approach. Moreover, reverse carried out, findings validated through sensitivity assessments. This examined 11 that satisfied inclusion exclusion criteria. There significant difference abundance 144 By employing MR technique, 13 bacteria pinpointed as having causal (including 3 unknown taxa). Even after Bonferroni correction, protective phylum Proteobacteria genus Dialister (Sequeira et al. Nat Microbiol. 5:304-313, 2020; Liu EBioMedicine. 90:104527, 2023) harmful Akkermansia, family Verrucomicrobiaceae, order Verrucomicrobia class Verrucomicrobiae remained significant. No noticeable heterogeneity or horizontal pleiotropy detected (IVs). However, investigations failed reveal any substantial relationship GM. Differences among healthy controls are explored studies. We verified possible connection certain genetically modified genera DN, thereby emphasizing "gut-kidney" axis new insights GM's role pathogenesis underlying Investigations this association necessary, novel biomarkers development targeted preventive strategies against needed.

Язык: Английский

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