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Frontiers in Endocrinology 2022
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans
PubMed: 36120444
DOI: 10.3389/fendo.2022.1011665 -
Frontiers in Bioscience (Scholar... May 2022Chronic kidney disease is generally progressive and currently has no reliable treatment to reverse a decline in kidney function or to slow the progression of the... (Review)
Review
Chronic kidney disease is generally progressive and currently has no reliable treatment to reverse a decline in kidney function or to slow the progression of the disease. Diabetic nephropathy is one of the leading causes of end-stage kidney failure. Kidney damage in diabetic nephropathy is largely attributed to the increased oxidative stress, affecting its metabolic activity, metabolic pathways, and hemodynamic pathways. In diabetic patients, hyperglycemia causes an increase in the production of reactive oxygen species that further increase oxidative stress. These reactive oxygen species are created through a variety of pathways, providing the opportunity for treatment using anti-oxidative defense mechanisms to prevent vascular injury. This review will give an overview of oxidative stress, along with the current treatments and limitations of diabetic nephropathy. We will also discuss the potential of antioxidative therapies, with an emphasis on the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
Topics: Antioxidants; Diabetes Mellitus; Diabetic Nephropathies; Humans; Hyperglycemia; Kidney; Oxidative Stress; Reactive Oxygen Species
PubMed: 35730439
DOI: 10.31083/j.fbs1402014 -
Frontiers in Endocrinology 2023Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is the most significant microvascular complication of diabetes and poses a severe public health... (Review)
Review
Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is the most significant microvascular complication of diabetes and poses a severe public health concern due to a lack of effective clinical treatments. Autophagy is a lysosomal process that degrades damaged proteins and organelles to preserve cellular homeostasis. Emerging studies have shown that disorder in autophagy results in the accumulation of damaged proteins and organelles in diabetic renal cells and promotes the development of DN. Autophagy is regulated by nutrient-sensing pathways including AMPK, mTOR, and Sirt1, and several intracellular stress signaling pathways such as oxidative stress and endoplasmic reticulum stress. An abnormal nutritional status and excess cellular stresses caused by diabetes-related metabolic disorders disturb the autophagic flux, leading to cellular dysfunction and DN. Here, we summarized the role of autophagy in DN focusing on signaling pathways to modulate autophagy and therapeutic interferences of autophagy in DN.
Topics: Humans; Diabetic Nephropathies; Kidney; Signal Transduction; Epithelial Cells; Autophagy; Diabetes Mellitus
PubMed: 37020591
DOI: 10.3389/fendo.2023.1139444 -
Frontiers in Endocrinology 2023Diabetic nephropathy (DN) is a prevalent and debilitating disease that represents the leading cause of chronic kidney disease which imposes public health challenges...
BACKGROUND
Diabetic 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.
METHODS
This 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.
RESULTS
This study identified 13 SDECGs between DN and normal groups which positively regulated immune cells. We also identified five feature genes (, , , , and ) 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.
CONCLUSION
TMJT 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.
Topics: Humans; Diabetic Nephropathies; Epidermal Growth Factor; Molecular Docking Simulation; Cluster Analysis; Databases, Factual; Diabetes Mellitus
PubMed: 38027201
DOI: 10.3389/fendo.2023.1172226 -
Gene Dec 2023Age-related macular degeneration (AMD) currently stands as the leading cause of irreversible vision loss in the present era. The primary objective of this study was to...
PURPOSE
Age-related macular degeneration (AMD) currently stands as the leading cause of irreversible vision loss in the present era. The primary objective of this study was to investigate the causal relationships between diabetic nephropathy (DN), its associated risk factors, and AMD among participants of European descent.
METHODS
Genetic variants associated with DN and its risk factors, encompassing glycemic traits, lipidemic traits, systolic/diastolic blood pressure, obesity, and urate, were obtained from previously published genome-wide association studies. Summary-level statistics for AMD were acquired from the FinnGen database. Univariable and multivariable Mendelian randomization (MR) were employed to conduct this investigation.
RESULTS
Our MR analyses indicated that per 1-standard deviation (SD) increase of DN heightened the risk of overall AMD (p = 1.03 × 10, OR = 1.24). And these findings remained consistent when examining both dry AMD (p = 2.27 × 10, OR = 1.17) and wet AMD (p = 5.15 × 10, OR = 1.33). Additionally, there was a causal association between high-density lipoprotein-cholesterol (HDL-C) levels and an increased risk of AMD (p = 2.69 × 10, OR = 1.23), while triglycerides were found to mitigate the risk (p = 0.02, OR = 0.83). Notably, no significant associations were observed between other risk factors of DN and AMD.
CONCLUSIONS
These findings suggest that the impact of DN on the development of AMD may be more substantial than previously believed. Furthermore, elevated HDL-C levels appear to heighten the risk of AMD, whereas triglycerides may provide a protective effect.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Diabetic Nephropathies; Cholesterol, HDL; Risk Factors; Triglycerides; Macular Degeneration; Polymorphism, Single Nucleotide; Diabetes Mellitus
PubMed: 37689221
DOI: 10.1016/j.gene.2023.147787 -
Chemistry & Biodiversity Oct 2022Diabetes is linked with various microvascular and macrovascular complications. Nephropathy, neuropathy and retinopathy are important microvascular complications of... (Review)
Review
Diabetes is linked with various microvascular and macrovascular complications. Nephropathy, neuropathy and retinopathy are important microvascular complications of diabetes. Different types of secondary metabolites including glycosides have been studied for their effects in diabetic complications. Various glycosides such as flavanoid glycosides and saponin glycosides are reported for their beneficial effects in diabetic nephropathy, neuropathy, retinopathy and cardiomyopathy by action on various pathways involved in the progression of these complications. Coumarin glycosides and cryanogenic glycosides have been studied for their effective role in diabetic nephropathy. Phenolic glycosides and anthraquinone glycosides also have beneficial role in diabetic neuropathy. The present review focuses on various classes of glycosides and their role in the prevention and treatment of vascular complications of diabetes.
Topics: Humans; Diabetic Nephropathies; Glycosides; Diabetes Complications; Cardiovascular Diseases; Retinal Diseases; Coumarins; Anthraquinones; Saponins; Diabetes Mellitus, Type 2
PubMed: 36181446
DOI: 10.1002/cbdv.202200067 -
Frontiers in Endocrinology 2023Diabetes nephropathy (DN) is a growing public health concern worldwide. Renal dysfunction impairment in DN is intimately linked to ER stress and its related signaling...
BACKGROUNDS
Diabetes nephropathy (DN) is a growing public health concern worldwide. Renal dysfunction impairment in DN is intimately linked to ER stress and its related signaling pathways. Nonetheless, the underlying mechanism and biomarkers for this function of ER stress in the DN remain unknown.
METHODS
Microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database, and ER stress-related genes (ERSRGs) were downloaded from the MSigDB and GeneCards database. We identified hub ERSRGs for DN progression by intersecting ERSRGs with differentially expressed genes and significant genes in WGCNA, followed by a functional analysis. After analyzing hub ERSRGs with three machine learning techniques and taking the intersection, we did external validation as well as developed a DN diagnostic model based on the characteristic genes. Immune infiltration was performed using CIBERSORT. Moreover, patients with DN were then categorized using a consensus clustering approach. Eventually, the candidate ERSRGs-specific small-molecule compounds were defined by CMap.
RESULTS
Several biological pathways driving pathological injury of DN and disordered levels of immune infiltration were revealed in the DN microarray datasets and strongly related to deregulated ERSRGs by bioinformatics multi-chip integration. Moreover, CDKN1B, EGR1, FKBP5, GDF15, and MARCKS were identified as ER stress signature genes associated with DN by machine learning algorithms, demonstrating their potential as DN biomarkers.
CONCLUSIONS
Our research sheds fresh light on the function of ER stress in DN pathophysiology and the development of early diagnostic and ER stress-related treatment targets in patients with DN.
Topics: Humans; Receptors, Estrogen; Diabetic Nephropathies; Biomarkers; Computational Biology; Endoplasmic Reticulum Stress; Machine Learning; Diabetes Mellitus
PubMed: 37745718
DOI: 10.3389/fendo.2023.1206154 -
Frontiers in Endocrinology 2024Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship...
CONTEXT
Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship between the severity of DR and the pathological severity of diabetic glomerulopathy remains unclear.
OBJECTIVE
To investigate the relationship between severity of diabetic retinopathy (DR) and histological changes and clinical indicators of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM).
METHODS
Patients with T2DM (n=272) who underwent a renal biopsy were eligible. Severity of DR was classified as non-diabetic retinopathy, non-proliferative retinopathy, and proliferative retinopathy (PDR). Relationship between DN and DR and the diagnostic efficacy of DR for DN were explored.
RESULTS
DN had a higher prevalence of DR (86.4%) and DR was more severe. The sensitivity and specificity of DR in DN were 86.4% and 78.8%, while PDR was 26.4% and 98.5%, respectively. In DN patients, the severity of glomerular lesions (p=0.001) and prevalence of KW nodules (p<0.001) significantly increased with increasing severity of DR. The presence of KW nodules, lower hemoglobin levels, and younger age were independent risk factors associated with more severe DR in patients with DN.
CONCLUSION
DR was a good predictor of DN. In DN patients, the severity of DR was associated with glomerular injury, and presence of KW nodules, lower hemoglobin levels and younger age were independent risk factors associated with more severe DR.
TRIAL REGISTRATION
ClinicalTrails.gov, NCT03865914.
Topics: Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Risk Factors; Hemoglobins
PubMed: 38344659
DOI: 10.3389/fendo.2024.1292412 -
Frontiers in Endocrinology 2023Diabetic nephropathy (DN) is a serious microvascular consequence of diabetes mellitus (DM), posing an encumbrance to public health worldwide. Control over the onset and... (Review)
Review
Diabetic nephropathy (DN) is a serious microvascular consequence of diabetes mellitus (DM), posing an encumbrance to public health worldwide. Control over the onset and progress of DN depend heavily on early detection and effective treatment. DN is a major contributor to end-stage renal disease, and a complete cure is yet to be achieved with currently available options. Though some therapeutic molecules have exhibited promise in treating DN complications, their poor solubility profile, low bioavailability, poor permeation, high therapeutic dose and associated toxicity, and low patient compliance apprehend their clinical usefulness. Recent research has indicated nano-systems as potential theranostic platforms displaying futuristic promise in the diagnosis and treatment of DN. Early and accurate diagnosis, site-specific delivery and retention by virtue of ligand conjugation, and improved pharmacokinetic profile are amongst the major advantages of nano-platforms, defining their superiority. Thus, the emergence of nanoparticles has offered fresh approaches to the possible diagnostic and therapeutic strategies regarding DN. The present review corroborates an updated overview of different types of nanocarriers regarding potential approaches for the diagnosis and therapy of DN.
Topics: Humans; Diabetic Nephropathies; Nanomedicine; Kidney Failure, Chronic; Glomerular Filtration Rate; Precision Medicine; Diabetes Mellitus
PubMed: 38027185
DOI: 10.3389/fendo.2023.1236686 -
Frontiers in Endocrinology 2023
Topics: Humans; Diabetic Nephropathies; Kidney Failure, Chronic; Diabetes Mellitus, Type 2
PubMed: 36742398
DOI: 10.3389/fendo.2023.1142285