Dynamic changes of inflammatory markers in the early stages of chronic kidney disease in patients with type 1 diabetes mellitus DOI Creative Commons
М. В. Осиков, Л. А. Эфрос,

L.Y. Zhuravleva

et al.

Bulletin of Russian State Medical University, Journal Year: 2024, Volume and Issue: 2024(6)

Published: Dec. 1, 2024

Diabetes mellitus (DM) is one of the major factors contributing to development and aggravation chronic kidney disease (CKD). The accurate convenient markers for early detection, estimation progression, adequate control CKD therapy in individuals with DM are limited glomerular filtration rate (GFR) albuminuria. Given role inflammation pathogenesis CKD, study aimed assess indicators correlation those GFR patients type 1 (T1D) stage CKD. involved healthy (n = 14), T1D showing no signs 30), as well 60), 2 38), 3 31). was calculated using formula СКD-ЕРI (eGFR); serum levels IL1β TNFα, C-reactive protein (CRP), ceruloplasmin (CP) were determined by enzyme immunoassay; neutrophil-to-lymphocyte index leukocyte intoxication (LII) calculated. It has been found that concentrations IL1β, CRP, CP elevated; LII increased. acute phase response severity progresses reaches its maximum 3b when concentration increased 2.4-fold (р 0.042), TNFα 34% 0.005), CRP 33-fold < 0.000), 73% 0.008), 8.4-fold 5-fold 0.013). integral function indicator, eGFR, decreases increasing above indicators. Thus, CP, LII, can be considered affordable informative inflammation, which increase progression T1D.

Language: Английский

Renoprotective mechanisms of celastrol in high glucose-mediated HK-2 cell injury through inhibition of the PI3K/Akt/NF-κB signalling pathway DOI

Xiaojuan Wang,

Mohamad Hafizi Abu Bakar, Mohd Asyraf Kassim

et al.

Biochemistry and Biophysics Reports, Journal Year: 2025, Volume and Issue: 41, P. 101928 - 101928

Published: Jan. 28, 2025

Language: Английский

Citations

3
Identification of key antifibrotic targets FPR1, TAS2R5, and LRP2BP of valsartan in diabetic nephropathy: A transcriptomics-driven study integrating machine learning, molecular docking, and dynamics simulations DOI

Zewen Wang,

Anlei Yuan,

Chaoqun Liu

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 297, P. 139842 - 139842

Published: Jan. 13, 2025

Language: Английский

Citations

1
Single-cell atlas reveals multi-faced responses of losartan on tubular mitochondria in diabetic kidney disease DOI Creative Commons
Zhen Zhu, Guangxin Luan, Song Wu

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 21, 2025

Mitochondria are crucial to the function of renal tubular cells, and their dynamic perturbation in many aspects is an important mechanism diabetic kidney disease (DKD). Single-nucleus RNA sequencing (snRNA-seq) technology a high-throughput analysis technique for at level single cell nucleus. Here, our DKD mouse single-cell conveys more comprehensive mitochondrial profile, which helps us further understand therapeutic response this unique organelle family drugs. After high fat diet (HFD), mice were intraperitoneally injected with streptozotocin (STZ) induce DKD, then divided into three subsets: CON (healthy) subset, (vehicle) LST (losartan; 25 mg/kg/day) subset. Divide HK-2 LG (low glucose; 5 mM) HG (high 30 + 1 µ M) subsets. snRNA-seq was performed on tissues subset mice. To reveal effects losartan gene pathway changes mitochondria, Gene Ontology (GO) enrichment GSEA/GSVA scoring analyze specific proximal (PT) mitochondria treatment, including key events homeostasis such as morphology, dynamics, mitophagy, autophagic flux, respiratory chain, apoptosis, ROS generation. Preliminary validation through vitro vivo experiments, observation morphology dynamics using probes Mitotracker Red, evaluation effect electron microscopy, laser confocal immunofluorescence, Western blotting. Detection flux cells by transfecting Ad-mCherry-GFP-LC3B dual fluorescence labeled adenovirus. Various fluorescent energy detector used detect ROS, respiration mitochondrion. Through atlas kidneys, it found that treatment significantly increased percentage PT cells. differentially expressed genes showed autophagy mitochondrion pathway. Further GSEA GSVA revealed mitophagy other events, production, membrane potential, adenosine triphosphate (ATP) synthesis, involved protective thereby improving homeostasis. Consistent results also obtained cellular experiments. In addition, we highlighted subpopulation phenotype data, preliminarily validated co-localization expression Pink1 Gclc specimens patients treated losartan. Our research suggests scRNA-seq can reflect multifaceted landscape after drug these findings may provide new targets therapy level.

Language: Английский

Citations

1
Lgals3 Promotes Calcium Oxalate Crystal Formation and Kidney Injury Through Histone Lactylation‐Mediated FGFR4 Activation DOI Creative Commons
Zehua Ye,

Yushi Sun,

Songyuan Yang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract The incidence of kidney stones is increasing worldwide. However, the underlying mechanism process stone formation and damage caused are not well understood. Here, it observed that Lgals3, a β‐galactoside‐binding protein, significantly increased in tissues with calcium oxalate (CaOx) stones, both vivo vitro models. Lgals3 expression positively correlated deposition CaOx crystals. Knockout markedly reduces crystal renal fibrosis vivo. Furthermore, deficiency decrease glycolytic rate lactate production during inhibited histone lactylation H3K18la. Mechanistic studies shows directly interacted key glycolysis protein pyruvate kinase M2 (PKM2) promoted its by modulating E3 ligase Trim21, preventing ubiquitination PKM2. H3K18 injury vitro. inhibites transcription, activation, FGFR4 through inhibition These findings suggest may play role interacting PKM2 promoting H3K18la‐mediated gene transcription activation.

Language: Английский

Citations

1
Inhibition of Drp1-mediated mitochondrial fission by P110 ameliorates renal injury in diabetic nephropathy DOI
Ruchi Yue,

Ziyu Yan,

Hongchu Zha

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 152, P. 114342 - 114342

Published: March 3, 2025

Language: Английский

Citations

1
Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases DOI Creative Commons

Aditya Dipakrao Hajare,

Neha Dagar, Anil Bhanudas Gaikwad

et al.

Molecular Biomedicine, Journal Year: 2025, Volume and Issue: 6(1)

Published: March 22, 2025

Abstract Klotho, initially introduced as an anti-aging protein, is expressed in the brain, pancreas, and most prominently kidney. The two forms of Klotho (membrane-bound soluble form) have diverse pharmacological functions such anti-inflammatory, anti-oxidative, anti-fibrotic, tumour-suppressive etc. membrane-bound form plays a pivotal role maintaining kidney homeostasis by regulating fibroblast growth factor 23 (FGF 23) signalling, vitamin D metabolism phosphate balance. deficiency has been linked with significantly reduced protection against various pathological phenotypes, including diabetic disease (DKD), which major cause chronic leading to end-stage disease. Owing pleiotropic actions klotho, it shown beneficial effects DKD tackling complex pathophysiology reducing inflammation, oxidative stress, well fibrosis. Moreover, protective effect klotho extends beyond other conditions, cardiovascular diseases, alzheimer's disease, cancer, inflammatory bowel liver Therefore, this review summarizes relationship between expression diseases special emphasis on DKD, distinct mechanisms potential exogenous supplementation therapeutic strategy. Future research into could unravel novel treatment avenues for diseases.

Language: Английский

Citations

1
Mitochondrial regulation in the tumor microenvironment: targeting mitochondria for immunotherapy DOI Creative Commons
Minseo Ahn,

Akhtar Ali,

Jae Ho Seo

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 11, 2024

Mitochondrial regulation plays a crucial role in cancer immunity the tumor microenvironment (TME). Infiltrating immune cells, including T natural killer (NK) and macrophages, undergo mitochondrial metabolic reprogramming to survive harsh conditions of TME enhance their antitumor activity. On other hand, immunosuppressive cells like myeloid-derived suppressor (MDSCs), regulatory (Tregs), mast tumor-associated macrophages (TAMs) rely on maintain function as well. Additionally, facilitates evasion even hijacks mitochondria from function. Recent studies suggest that targeting can synergistically reduce progression, especially when combined with traditional therapies checkpoint inhibitors. Many mitochondrial-targeting drugs are currently clinical trials have potential efficacy immunotherapy. This mini review highlights critical provides lists

Language: Английский

Citations

5
Higher Circulating Neutrophil Counts Is Associated with Increased Risk of All-Cause Mortality and Cardiovascular Disease in Patients with Diabetic Kidney Disease DOI Creative Commons

Ruiyan Xie,

David Bishai, David Tak Wai Lui

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1907 - 1907

Published: Aug. 20, 2024

Accumulating evidence has suggested the pathogenic roles of chronic inflammation and neutrophils in diabetic kidney disease (DKD). This study investigated relationship between neutrophils, all-cause, cardiovascular (CVD) mortality type 2 diabetes mellitus (T2DM) patients with DKD.

Language: Английский

Citations

4
Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism DOI Creative Commons
Phoom Narongkiatikhun, Ye Ji Choi,

Hailey Hampson

et al.

Kidney International Reports, Journal Year: 2024, Volume and Issue: 9(12), P. 3386 - 3402

Published: Oct. 4, 2024

Language: Английский

Citations

4
Protective effects of Notoginsenoside R2 on reducing lipid accumulation and mitochondrial dysfunction in diabetic nephropathy through regulation of c-Src DOI Creative Commons

Xieyi Guo,

Liu Yang,

Xiao-Ning An

et al.

Chinese Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 15, 2025

Abstract Background The treatment options to delay the progression of diabetic nephropathy (DN), a key contributor chronic kidney disease (CKD), are urgently needed. Previous studies reported that traditional Chinese medicine Panax notoginseng (PNG) exerted beneficial effects on DN. However, renoprotective Notoginsenoside R2 (NR2), an active component PNG, DN have not been investigated. This study aimed assess therapeutic potential NR2 in and explore its underlying mechanisms. Methods In vivo models were developed using db/db mice, while vitro utilized HK-2 cells exposed high glucose palmitic acid (HGPA). Online databases Cytoscape software employed predict targets NR2. expression associated proteins was measured immunohistochemistry western blot. Lipid accumulation, oxidative stress levels, mitochondrial function cell apoptosis also assessed. Small interfering RNA used experiments examine effect c-Src. Results ameliorated albuminuria, renal pathology mice. activation c-Src suppressed mice HGPA. inhibited JNK/STAT1 phosphorylation CD36 overexpression. lipid stress, dysfunction vitro. By inhibiting c-Src, HGPA experienced less deposition damage, indicating correlated with inhibition Conclusion delayed partly through suppression protective might be related reduction accumulation. Graphical

Language: Английский

Citations

0