Causal association of plasma circulating metabolites with nephritis: a Mendelian randomization study

Frontiers in Nutrition, Год журнала: 2024, Номер 11

Опубликована: Май 3, 2024

Nephritis is a pivotal catalyst in chronic kidney disease (CKD) progression. Although epidemiological studies have explored the impact of plasma circulating metabolites and drugs on nephritis, few harnessed genetic methodologies to establish causal relationships. Through Mendelian randomization (MR) two substantial cohorts, spanning large sample sizes, we evaluated over 100 263 discern their effects nephritis risk. The primary analytical tool was inverse variance weighted (IVW) analysis. Our bioinformatic scrutiny GSE115857 (IgA nephropathy, 86 samples) GSE72326 (lupus 238 unveiled anomalies lipid metabolism immunological characteristics nephritis. Thorough sensitivity analyses (MR-Egger, MR-PRESSO, leave-one-out analysis) were undertaken verify instrumental variables' (IVs) assumptions. Unique lipoprotein-related molecules established links with diverse subtypes. Notably, docosahexaenoic acid (DHA) emerged as protective factor for acute tubulointerstitial (ATIN) (OR1 = 0.84, [95% CI 0.78-0.90], p1 0.013; OR2 0.89, 0.82-0.97], p2 0.007). Conversely, multivitamin supplementation minus minerals notably increased risk ATIN (OR 31.25, 9.23-105.85], p 0.004). Reduced α-linolenic (ALA) levels due lipid-lowering linked both 4.88, 3.52-6.77], < 0.001) (TIN) 7.52, 2.78-20.30], 0.042). While non-renal drug indivina showed promise TIN treatment, use digoxin, hydroxocobalamin, liothyronine elevated (CTIN). Transcriptome analysis affirmed that anomalous immune infiltration are characteristic IgA nephropathy lupus robustness these reinforced by tests, indicating no signs pleiotropy. Dyslipidemia significantly contributes development. Strategies aimed at reducing low-density lipoprotein or ALA may enhance efficacy existing regimens treatment. Renal functional status should also be judiciously considered regard nonrenal medications.

Язык: Английский

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Phenylsulfate-induced oxidative stress and mitochondrial dysfunction in podocytes are ameliorated by Astragaloside IV activation of the SIRT1/PGC1α /Nrf1 signaling pathway

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 117008 - 117008

Опубликована: Июнь 19, 2024

Astragaloside IV (AS-IV) exhibits diverse biological activities. Despite this, the detailed molecular mechanisms by which AS-IV ameliorates diabetic nephropathy (DN) and shields podocytes from oxidative stress (OS) mitochondrial dysfunction remain poorly understood. In this study, we used biochemical assays, histopathological analysis, Doppler ultrasound, transmission electron microscopy，flow cytometry, fluorescence staining, Western blotting other methods. was administered to db/db mice for in vivo experimentation. Our findings indicated that treatment significantly reduced diabetes-associated markers, proteinuria, kidney damage. It also diminished ROS levels kidney, enhanced expression of endogenous antioxidant enzymes, improved health. Phenyl sulfate (PS), a protein-bound uremic solute enteric origin, has been closely linked with DN represents promising avenue further research. vitro, PS exposure induced OS podocytes, increasing while decreasing enzyme activity (Catalase, Heme Oxygenase-1, Superoxide Dismutase, Glutathione Peroxidase). inhibitors (N-acetyl-L-cysteine, NAC) as positive control group can reduce restore enzymes protein levels. Additionally, markers associated biosynthesis function (SIRT1, PGC1α, Nrf1, TFAM). These adverse effects were partially reversed treatment. However, co-treatment SIRT1 inhibitor EX527 failed these indicators. Overall, our study demonstrates effectively attenuates mitigates PS-induced via SIRT1/PGC1α/Nrf1 pathway.

Язык: Английский

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Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease

Pharmaceuticals, Год журнала: 2024, Номер 17(4), С. 418 - 418

Опубликована: Март 26, 2024

Diabetic kidney disease is a frequent microvascular complication of diabetes and currently the leading cause chronic end-stage worldwide. Although prevalence other complications falling, number diabetic patients with in need replacement therapy rising. In addition, these have extremely high cardiovascular risk. It more than evident that there unmet treatment disease. Finerenone novel nonsteroidal mineralocorticoid receptor antagonist used for treating has predominant anti-fibrotic anti-inflammatory effects exhibits several renal cardiac protective effects. This review article summarizes current knowledge future prospects finerenone

Язык: Английский

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Kidney tea [Orthosiphon aristatus (Blume) Miq.] improves diabetic nephropathy via regulating gut microbiota and ferroptosis

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июнь 19, 2024

Introduction Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Due to its complex pathogenesis, new therapeutic agents are urgently needed. Orthosiphon aristatus (Blume) Miq., commonly known as kidney tea, widely used in DN treatment China. However, mechanisms have not been fully elucidated. Methods We db/db mice model and evaluated efficacy tea by measuring fasting blood glucose (FBG), serum inflammatory cytokines, injury indicators histopathological changes. Furthermore, 16S rDNA gene sequencing, untargeted metabolomics, electron microscope, ELISA, qRT-PCR, Western blotting were performed explore which exerted effects. Results Twelve polyphenols identified from extract ameliorated FBG, inflammation mice. Moreover, reshaped gut microbiota, reduced abundance Muribaculaceae , Lachnoclostridium Prevotellaceae_UCG-001 Corynebacterium Akkermansia enriched Alloprevotella Blautia Lachnospiraceae_NK4A136_group . Kidney altered levels metabolites pathways such ferroptosis, arginine biosynthesis mTOR signaling pathway. Importantly, improved mitochondrial damage, increased SOD activity, decreased MDA 4-HNE tissues Meanwhile, this functional upregulated GPX4 FTH1 expression downregulated ACSL4 NCOA4 expression, indicating that it could inhibit ferroptosis kidneys. Conclusion Our findings imply can attenuate development modulating microbiota presents a novel scientific rationale for clinical application tea.

Язык: Английский

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Causal relationship between gut microbiota and autoimmune thyroiditis: A mendelian study

Heliyon, Год журнала: 2024, Номер 10(3), С. e25652 - e25652

Опубликована: Фев. 1, 2024

BackgroundAutoimmune thyroiditis (AIT), also known as Hashimoto's (HT) or chronic lymphocytic thyroiditis, is a prevalent autoimmune disorder. Despite its high prevalence, the pathogenesis of AIT remains unclear. Previous studies have suggested potential association between gut microbiota and AIT. However, whether this relationship causal coincidental uncertain. To address gap in knowledge, our study aimed to investigate using two-sample Mendelian randomization (MR) method.MethodsSummary-level data comprising 211 taxa (131 genera, 35 families, 20 orders, 16 classes, 9 phyla) were obtained from comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases extracted UK Biobank, FinnGen study, various extensive GWAS studies. A meticulous MR analysis was conducted evaluate genetically predicted these diseases. Sensitivity analyses tests for heterogeneity systematically performed validate reliability findings.ResultsSix species showed significant according IVW method. Among them, following exhibited negative AIT: family Alcaligenaceae, Pasteurellaceae (ID: 3689), Peptococcaceae, genus Lachnospira, Victivallis, order Pasteurellales 3688). No evidence pleiotropy detected.ConclusionThe uncovered at genetic prediction level specific These findings offer novel insights into mechanisms governing development mediated by microbiota. This knowledge could inform design future interventions, potentially involving microbiome-related strategies, associated development.

Язык: Английский

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Association of dietary live microbe intake with diabetic kidney disease in patients with type 2 diabetes mellitus in US adults: a cross-sectional study of NHANES 1999–2018

Acta Diabetologica, Год журнала: 2024, Номер 61(6), С. 705 - 714

Опубликована: Фев. 24, 2024

Abstract Aims Several studies have reported dietary microorganisms’ beneficial effects on human health. We aimed to detect the potential association between live microbe intake and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) through a cross-sectional analysis of National Health Nutrition Examination Survey from 1999 2018. Methods According Sanders classification system microbes, study participants were divided into three groups: low, medium, high groups. In T2DM, DKD was assessed by glomerular filtration rate (< 60 mL/min/1.73 m using Chronic Kidney Disease Epidemiology Collaboration algorithm), proteinuria (urinary albumin creatinine ratio ≥ 30 mg/g), or both. Weighted univariate multivariate logistic regression subgroup analyses conducted investigate independent DKD. Results The included 3836 participants, whom 1467 (38.24%) had for diagnosis. Our demonstrated that group more likely be older, female, non-Hispanic White, higher education levels, lower prevalence smoking, poverty-income ratio, energy intake, haemoglobin (HbA1c) serum risk progression. After adjustment covariates, low DKD, whereas no significant found medium No statistically interaction observed all except HbA1c ( p < 0.05). Conclusions results indicate associated prevalence.

Язык: Английский

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Association between gut microbiota and diabetic nephropathy: a mendelian randomization study

Frontiers in Microbiology, Год журнала: 2024, Номер 15

Опубликована: Март 27, 2024

Background The correlation between diabetic nephropathy (DN) and gut microbiota (GM) has been suggested in numerous animal experiments cross-sectional studies. However, a causal association GM DN not ascertained. Methods This research adopted MR analysis to evaluate the link derived from data acquired through publicly available genome-wide studies (GWAS). study utilized inverse variance weighted (IVW) approach assess DN. Four additional methods including MR-Egger, median, mode, simple mode were employed ensure comprehensive robust results. Cochran’s Q test MR-Egger method conducted identify heterogeneity horizontal pleiotropy, respectively. leave-one-out was stability of Finally, reverse performed Results According IVW analysis, Class Verrucomicrobiae ( p = 0.003), Order Verrucomicrobiales Family Verrucomicrobiaceae Genus Akkermansia Catenibacterium 0.031), Coprococcus 1 0.022), Eubacterium hallii group 0.018), Marvinbryantia 0.023) associated with higher risk On contrary, Actinobacteria 0.037), Group ventriosum 0.030), Ruminococcus gauvreauii 0.048), Lactobacillales 0.045), Phylum Proteobacteria 0.017) lower sensitivity did any substantial pleiotropy or outcomes. We found effects on 11 species analysis. Notably, are mutually causalities. Conclusion identified which may enhance understanding intestinal-renal axis provide novel potential targets for early non-invasive diagnosis treatment

Язык: Английский

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Gut microbiota profiling reflects the renal dysfunction and psychological distress in patients with diabetic kidney disease

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Июль 15, 2024

Background The gut microbiota plays a pivotal role in the development of diabetes and kidney disease. However, it is not clear how intestinal microecological imbalance involved context diabetic disease (DKD), leading cause renal failure. Objectives To elucidate microbial signatures associated with DKD progression towards end-stage (ESRD) explore whether they could reflect dysfunction psychological distress. Methods A cross-sectional study was conducted to 29 non-ESRD patients 19 ESRD compared 20 healthy controls. Differential analysis performed detect distinct alterations diversities taxon abundance without ESRD. Renal estimated by urea, creatinine, glomerular filtration rate. Psychological distress assessed using Self-Rating Anxiety Scale, Depression Hamilton Rating Scale. Results Alpha diversity indexes were reduced patients, particularly those Beta revealed that compositions different individuals whereas similar observed patients. Taxon differential showed when controls, exhibit profiles including abundances butyrate-produced, anti-inflammatory bacteria Faecalibacterium , Lachnospira Roseburia Lachnoclostridium increased pro-inflammatory Collinsella Streptococcus etc. These distinctive genera presented consistent associations dysfunction, as well distress, especially Conclusions who have progressed ESRD, unique characteristics their are both may be significant factor deterioration its eventual

Язык: Английский

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Curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 6, 2025

The aim of this study was to investigate the effect curcumin nanocrystals (Cur-NCs) on ferroptosis in high-glucose (HG)-induced HK-2 cells and streptozotocin (STZ)-induced diabetic nephropathy model (DN) rats. purpose is determine whether Cur NCs can become a promising treatment option for diabetes by reducing ferroptosis. Cur-NCs were prepared using microfluidic technology studied dynamic light scattering transmission electron microscopy. treated with 30 mM HG create renal tubule damage cell model. Then, viability evaluated varying concentrations (0.23, 0.47, 0.94, 1.87, 3.75, 7.5, 15, μg/mL) Cell Counting Kit-8 (CCK-8). Furthermore, vivo experiments carried out roles STZ-induced DN results showed that greatly enhanced levels LDH, MDA, Iron, lipid ROS, apoptosis, NCOA4, TFR-1, while decreasing expression GSH, GPX4, SLC7A11, FTH-1. These effects induced could be attenuated Cur-NCs. also reduced HG-induced decrease viability, as well increase ROS however erastin inhibit their effects. inhibited This demonstrates significantly attenuate recovering implying may therapy DN.

Язык: Английский

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Astragalus Mongholicus Polysaccharides Alleviate Kidney Injury in Rats with Type 2 Diabetes Through Modulation of Oxidation, Inflammation, and Gut Microbiota

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1470 - 1470

Опубликована: Фев. 10, 2025

We aimed to uncover the underlying mechanisms contributing therapeutic efficacy of Astragalus mongholicus Polysaccharides (mAPS) in alleviating diabetic nephropathy (DN). The rat model DN was subjected a high-sugar and high-fat diet (HSHFD) coupled with streptozotocin (STZ) injection. Our findings revealed that mAPS administration decreased fasting blood glucose (FBG), BUN, SCR, UA, MDA levels, while elevating serum GSH, GSH-PX, SOD activities rats (p < 0.05). Furthermore, there notable rise mRNA protein expression renal Nrf-2, GCLC, NQO1, HO-1 post treatment Additionally, supplementation led reduced TLR4, NLRP3, p-NF-κB, TGF-β, Smad4. Concurrently, exerted modulatory effect on gut microbiota, as evidenced by increased abundance Muribaculaceae, Ruminococcus_1, Phascolarctobacterium, Lachnoclostridium-related genera. Spearman correlation analysis illustrated negative association between microbiota (Muribaculaceae, Lachnospiraceae_NK4A136, Clostridiales) levels parameters (BUN, CR, TC, TG). In summary, our data robustly attests potential modulating oxidative stress, inflammation, ultimately resulting improved function rats.

Язык: Английский

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