Identification of ferroptosis-related genes as potential diagnostic biomarkers for diabetic nephropathy based on bioinformatics

Guo, Binbin; Li, Minhui; Wu, Peipei; Chen, Yan

doi:10.3389/fmolb.2023.1183530

Cited by 3 publications

(2 citation statements)

References 44 publications

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“…Importantly, our results showed that kidney tea mainly participated in ferroptosis, arginine biosynthesis and mTOR signaling pathway. Ferroptosis, an iron-dependent form of regulated cell death, is considered to be closely associated with DN pathogenesis ( Guo et al, 2023 ; Kim et al, 2023 ; Tsai et al, 2023 ). Attractively, emodin inhibited ferroptosis by promoting the expression of nuclear factor E2-related factor 2 (NRF2), thereby reducing reactive oxygen species (ROS) production and ameliorating renal injury in DN rats ( Ji et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

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

Zhou,

Niu,

Bian

et al. 2024

Front. Pharmacol.

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

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Section: Discussionmentioning

confidence: 99%

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

Zhou,

Niu,

Bian

et al. 2024

Front. Pharmacol.

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“…Previous network pharmacology studies (71, 72) on traditional Chinese medicine or Chinese herbal medicine for treating DN did not involve in-depth analysis of human samples but used animal samples or simply collected disease targets from GEO datasets. Previous machine learning studies (73)(74)(75) on DN mainly analyzed it from the perspectives of immunity, oxidative stress, programmed cell death, etc., and were mainly used to screen and identify genetic biomarkers, while this study used the target as a link and started from the perspective of drug intervention in disease to explore the multi-faceted mechanisms of TMJT in treating DN, and verified the results by dataset analysis, molecular docking, MR analysis, and other methods. Therefore, compared with other studies, this study is more comprehensive and has more guiding significance for clinical medication.…”

Section: The Strengths and Limitations Of This Studymentioning

confidence: 99%

Exploring the potential mechanisms of Tongmai Jiangtang capsules in treating diabetic nephropathy through multi-dimensional data

Liu,

Cui,

Zhang

et al. 2023

Front. Endocrinol.

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BackgroundDiabetic nephropathy (DN) is a prevalent and debilitating disease that represents the leading cause of chronic kidney disease which imposes public health challenges Tongmai Jiangtang capsule (TMJT) is commonly used for the treatment of DN, albeit its underlying mechanisms of action are still elusive.MethodsThis study retrieved databases to identify the components and collect the targets of TMJT and DN. Target networks were constructed to screen the core components and targets. Samples from the GEO database were utilized to perform analyses of targets and immune cells and obtain significantly differentially expressed core genes (SDECGs). We also selected a machine learning model to screen the feature genes and construct a nomogram. Furthermore, molecular docking, another GEO dataset, and Mendelian randomization (MR) were utilized for preliminary validation. We subsequently clustered the samples based on SDECG expression and consensus clustering and performed analyses between the clusters. Finally, we scored the SDECG score and analyzed the differences between clusters.ResultsThis study identified 13 SDECGs between DN and normal groups which positively regulated immune cells. We also identified five feature genes (CD40LG, EP300, IL1B, GAPDH, and EGF) which were used to construct a nomogram. MR analysis indicated a causal link between elevated IL1B levels and an increased risk of DN. Clustering analysis divided DN samples into four groups, among which, C1 and CI were mainly highly expressed and most immune cells were up-regulated. C2 and CII were the opposite. Finally, we found significant differences in SDECG scores between C1 and C2, CI and CII, respectively.ConclusionTMJT may alleviate DN via core components (e.g. Denudatin B, hancinol, hirudinoidine A) targeting SDECGs (e.g. SRC, EGF, GAPDH), with the involvement of feature genes and modulation of immune and inflammation-related pathways. These findings have potential implications for clinical practice and future investigations.

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Apoptosis and NETotic cell death affect diabetic nephropathy independently: An study integrative study encompassing bioinformatics, machine learning, and experimental validation

Cai,

Zeng,

Luo

et al. 2024

Genomics

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Identification of ferroptosis-related genes as potential diagnostic biomarkers for diabetic nephropathy based on bioinformatics

Cited by 3 publications

References 44 publications

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

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

Exploring the potential mechanisms of Tongmai Jiangtang capsules in treating diabetic nephropathy through multi-dimensional data

Apoptosis and NETotic cell death affect diabetic nephropathy independently: An study integrative study encompassing bioinformatics, machine learning, and experimental validation

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