Unveiling FOS as a Potential Diagnostic Biomarker and Emetine as a Prospective Therapeutic Agent for Diabetic Nephropathy DOI Creative Commons
Jiaqiong Lin, Xiaoyong Li, Yan Lin

и другие.

Journal of Inflammation Research, Год журнала: 2023, Номер Volume 16, С. 6139 - 6153

Опубликована: Дек. 1, 2023

Diabetic nephropathy (DN) is one of the primary causes end-stage renal disease, yet effective therapeutic targets remain elusive. This study aims to identify novel diagnostic biomarkers and potential candidates for DN.Differentially expressed genes (DEGs) in GSE96804 GSE142025 were identified functional enrichment analysis was performed. Diagnostic selected using machine learning algorithms evaluated by Receiver Operating Characteristic analysis. c-Fos expression validated an established DN mouse model. Immune infiltration levels assessed with Single-Sample Gene Set Enrichment Analysis. Co-expression revealed regulatory relationships involving FOS. cMAP predicted candidates. Transcriptome sequencing experiments RAW264.7 cells performed investigate molecular mechanisms emetine.In both datasets, we 44 upregulated 74 downregulated DEGs involved focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathway. FOS emerged as a robust marker decreased patients mouse. FOS, implicating MAPK pathway, regulation cell proliferation apoptotic pathways. dysregulation observed patients. Notably, emetine candidate. experimental validation demonstrated suppressed M1 macrophage polarization inhibiting activation NF-κB well reducing Il-18 Ccl5.In conclusion, our promising biomarker candidate DN. These findings enhance understanding pathogenesis present prospects strategies.

Язык: Английский

The roles of gut microbiota and its metabolites in diabetic nephropathy DOI Creative Commons
Hui Zhao,

Cheng-E Yang,

Tian Liu

и другие.

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Июль 27, 2023

Diabetic nephropathy (DN) is a severe microvascular complication of diabetes, which increases the risk renal failure and causes high global disease burden. Due to lack sustainable treatment, DN has become primary cause end-stage worldwide. Gut microbiota its metabolites exert critical regulatory functions in maintaining host health are associated with many pathogenesis aging-related chronic diseases. Currently, theory gut–kidney axis opened novel angle understand relationship between gut multiple kidney In recent years, accumulating evidence revealed that their play an essential role pathophysiologic processes through axis. this review, we summarize current investigations microbial involvement progression DN, further discuss potential microbiota-targeted therapeutic approaches for DN.

Язык: Английский

Процитировано

29

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

Junju Zou,

Hui Zhou

и другие.

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

Процитировано

11

Renal protective effects and mechanisms of Astragalus membranaceus for diabetic kidney disease in animal models: An updated systematic review and meta-analysis DOI Creative Commons
Meifang Liu,

Yuan Ming Di,

Brian H. May

и другие.

Phytomedicine, Год журнала: 2024, Номер 129, С. 155646 - 155646

Опубликована: Апрель 27, 2024

Astragalus membranaceus (AM) shows potential therapeutic benefits for managing diabetic kidney disease (DKD), a leading cause of failure with no cure. However, its comprehensive effects on renal outcomes and plausible mechanisms remain unclear. This systematic review meta‐analysis aimed to synthesize the AM in DKD animal models. Seven electronic databases were searched studies until September 2023. Risk bias was assessed based SYRCLE's Bias tool. Standardized mean difference (SMD) or (MD) estimated serum creatinine (SCr), blood urea nitrogen (BUN), albuminuria, histological changes, oxidative stress, inflammation, fibrosis glucolipids. Effects pooled using random‐effects Heterogeneity presented as I2. Subgroup analysis investigated treatment- animal-related factors outcomes. Publication funnel plots Egger's test. Sensitivity performed assess results' robustness. RevMan 5.3 Stata MP 15 software used statistical analysis. Forty involving 1,543 animals identified treatment significantly decreased SCr (MD = –19.12 μmol/L, 95% CI: –25.02 –13.23), BUN –6.72 mmol/L, –9.32 –4.12), urinary albumin excretion rate (SMD –2.74, –3.57, –1.90), changes –2.25, –3.19 –1.32). improved anti-oxidative stress expression 1.69, 0.97 2.41), inflammation biomarkers –3.58, –5.21 –1.95). also markers (i.e. TGF-β1, CTGF, collagen IV, Wnt4 β-catenin) increased anti-fibrosis marker BMP-7. Blood glucose, lipids size compared DM control group. could improve alleviate injury through multiple signaling pathways. indicates may be an option consider development future therapeutics.

Язык: Английский

Процитировано

9

Prognostic effect of neutrophil percentage-to-albumin ratio (NPAR) on all-cause and cardiovascular mortality in diabetic kidney disease (DKD): NHANES 1999–2018 DOI Creative Commons
Juntao Tan, Jinglong Du, Jiaxiu Liu

и другие.

Diabetology & Metabolic Syndrome, Год журнала: 2025, Номер 17(1)

Опубликована: Март 28, 2025

This study aimed to evaluate the associations between neutrophil percentage-to-albumin ratio (NPAR) and both all-cause cardiovascular mortality in diabetic kidney disease (DKD) patients. The data for this were sourced from National Health Nutrition Examination Survey (NHANES) 1999–2018. Weighted logistic regression, Cox proportional hazards model, Fine-Gray competing risk model used assess association NPAR DKD A total of 2,699 participants enrolled study. regression analysis revealed that elevated levels associated with a higher all (HR: 2.17, 95%CI: 1.83–2.58). Meanwhile, significant difference was observed males 1.83, 1.42–2.38) but not females. Finally, adjusted identified as an independent predictor (SHR: 1.86 1.28–2.72) In nationally representative sample US, detected increased mortality. addition, gender differences relationship also observed.

Язык: Английский

Процитировано

1

MicroRNA-204-5p Ameliorates Renal Injury via Regulating Keap1/Nrf2 Pathway in Diabetic Kidney Disease DOI Creative Commons

Jiajia Dong,

Mengyu Liu,

Yawei Bian

и другие.

Diabetes Metabolic Syndrome and Obesity, Год журнала: 2024, Номер Volume 17, С. 75 - 92

Опубликована: Янв. 1, 2024

Background: Diabetic kidney disease (DKD) is characterized by renal fibrosis, and the pathogenesis of fibrosis still not definitely confirmed. MiR-204-5p plays an important role in regulation autophagy oxidative stress. In this study, we aimed to investigate miR-204-5p on damage diabetic kidneys underlying mechanisms involved. Methods: vivo, AAV-Ksp-miR-204-5p mimics were injected into mice via tail vein. vitro, high glucose-induced HK-2 cells treated with inhibitor, mimics, ATG5 siRNA, tertiary butyl hydroquinone (TBHQ), ML385, or 3-Methyladenine (3-MA). FISH qRT-PCR used detect expression. The expressions protein mRNA detected Western blotting, immunofluorescence, immunohistochemistry qRT-PCR. concentration fibronectin culture medium was ELISA. Results: expression significantly inhibited than that control group. Delivering increased expression, improved function, stress, restored db/db mice. HG treatment cells. effectively reduced collagen I dysfunction, Nrf2 whereas these alterations abrogated inhibitor 3-methyladenine (3-MA, 5 mM) siRNA transfection HG-induced addition, aggravated decreased while abolished activator TBHQ. Furthermore, binding Keap1 confirmed luciferase reporter assay negatively regulated resulting activation pathway. Conclusion: MicroRNA-204-5p protects against progression restoring regulating Keap1/Nrf2 Keywords: disease, miR-204-5p, Keap1, Nrf2,

Язык: Английский

Процитировано

6

The therapeutic effects of marine sulfated polysaccharides on diabetic nephropathy DOI
Lijuan Wu, Xiaonan Zhang, Jun Zhao

и другие.

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 261, С. 129269 - 129269

Опубликована: Янв. 9, 2024

Язык: Английский

Процитировано

6

Dang-Gui-Bu-Xue decoction against diabetic nephropathy via modulating the carbonyl compounds metabolic profile and AGEs/RAGE pathway DOI
Zhi‐Tong Zhang, Yali Qi, Pan Chen

и другие.

Phytomedicine, Год журнала: 2024, Номер 135, С. 156104 - 156104

Опубликована: Сен. 29, 2024

Язык: Английский

Процитировано

6

Association of systemic immune-inflammation index with diabetic kidney disease in patients with type 2 diabetes: a cross-sectional study in Chinese population DOI Creative Commons
Pijun Yan,

Yuxia Yang,

Xing Zhang

и другие.

Frontiers in Endocrinology, Год журнала: 2024, Номер 14

Опубликована: Янв. 4, 2024

Systemic immune-inflammation index (SII), a novel inflammatory marker, has been reported to be associated with diabetic kidney disease (DKD) in the U.S., however, such close relationship DKD other countries, including China, not never determined. We aimed explore association between SII and Chinese population. A total of 1922 hospitalized patients type 2 diabetes mellitus (T2DM) included this cross-sectional study were divided into three groups based on estimated glomerular filtration rate (eGFR) urinary albumin-to-creatinine ratio (ACR): non-DKD group, stages 1-2 Alb DKD-non-Alb+DKD stage 3 group. The possible was investigated by correlation multivariate logistic regression analysis, receiver-operating characteristic (ROC) curves analysis. Moving from group level gradually increased (P for trend <0.01). Partial analysis revealed that positively ACR prevalence DKD, negatively eGFR (all P<0.01). Multivariate showed remained independently significantly presence after adjustment all confounding factors [(odds (OR), 2.735; 95% confidence interval (CI), 1.840-4.063; P < 0.01)]. Moreover, compared subjects lowest quartile (Q1), fully adjusted OR 1.060 (95% CI 0.773-1.455) Q2, 1.167 0.995-1.368) Q3, 1.266 1.129-1.420) highest (Q4) Similar results observed or DKD-non- Alb+DKD among quartiles. Last, ROC best cutoff values predict 1- 2, DKD-non-Alb+ 609.85 (sensitivity: 48.3%; specificity: 72.8%), 601.71 43.9%; 72.3%), 589.27 61.1%; 71.1%), respectively. Higher is an risk severity might promising biomarker its distinct phenotypes

Язык: Английский

Процитировано

5

Osthole ameliorates early diabetic kidney damage by suppressing oxidative stress, inflammation and inhibiting TGF-β1/Smads signaling pathway DOI
Qiangsheng Li, Yifei Wang, Yan Jia

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 133, С. 112131 - 112131

Опубликована: Апрель 25, 2024

Язык: Английский

Процитировано

5

PDK4-mediated Nrf2 inactivation contributes to oxidative stress and diabetic kidney injury DOI
Shasha Tian, Xiaopeng Yang, Yao Lin

и другие.

Cellular Signalling, Год журнала: 2024, Номер 121, С. 111282 - 111282

Опубликована: Июль 5, 2024

Язык: Английский

Процитировано

5