Role of Uremic Toxins in Vascular Inflammation Associated with Chronic Kidney Disease DOI Open Access

Rania Chermiti,

Stéphane Burtey, Laetitia Dou

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(23), P. 7149 - 7149

Published: Nov. 26, 2024

Cardiovascular disease (CVD) is a major complication of chronic kidney (CKD), despite improvements in patient care. Vascular inflammation crucial process the pathogenesis CVD and critical factor cardiovascular complications CKD patients. promotes pro-inflammatory environment that impacts vascular wall, leading to endothelial dysfunction, increased oxidative stress, remodeling. The uremic toxins accumulate as function declines are key contributors inflammatory processes. Our review will examine how leads inflammation, paving way CVD. We provide an overview mechanisms induced by toxins, with particular focus on those derived from tryptophan metabolism. These along their receptor, aryl hydrocarbon receptor (AHR), have emerged players linking thrombosis. A deeper understanding underlying CKD, particularly driven could reveal valuable therapeutic targets alleviate burden

Language: Английский

The role of matrix metalloproteinase 9 in fibrosis diseases and its molecular mechanisms DOI Creative Commons
Yuling Wang,

Linke Jiao,

Caoxia Qiang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116116 - 116116

Published: Jan. 5, 2024

Fibrosis is a process of tissue repair that results in the slow creation scar to replace healthy and can affect any or organ. Its primary feature massive deposition extracellular matrix (mainly collagen), eventually leading dysfunction organ failure. The progression fibrotic diseases has put significant strain on global health economy, as result, there an urgent need find some new therapies. Previous studies have identified inflammation, oxidative stress, cytokines, remodeling play crucial role are essential avenues for treating diseases. Among them, metalloproteinases (MMPs) considered main targets treatment since they driver involved ECM degradation, inhibitors (TIMPs) natural endogenous MMPs. Through previous studies, we found MMP-9 target However, it worth noting plays bidirectional regulatory different stages same disease. Previously inhibitors, such pirfenidone nintedanib, suffer from rather pronounced side effects, therefore, investigate drugs. In this review, explore mechanism action signaling pathways tissues organs, hoping provide ideas developing safer more effective biologics.

Language: Английский

Citations

28
Genetic deficiency or pharmacological inhibition of cGAS–STING signalling suppresses kidney inflammation and fibrosis DOI Open Access
Baihai Jiao,

Changlong An,

Hao Du

et al.

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Background and Purpose Chronic kidney disease (CKD) is characterised by inflammation, which can lead to tubular atrophy fibrosis. The molecular mechanisms are not well understood. In this study, we investigated the functional role of cyclic GMP–AMP synthase (cGAS)– stimulator interferon genes (STING) signalling in renal inflammation Experimental Approach Mice with global cGAS deficiency or myeloid cell‐specific STING wild‐type mice treated RU.521, a selective inhibitor, were used examine cGAS–STING fibrosis preclinical model obstructive nephropathy vivo. Bone marrow‐derived macrophages determine whether epithelial cell‐derived DNA activate vitro. Key Results Following injury, was activated kidneys during development exhibited significantly less macrophage proinflammatory activation, myofibroblast formation, total collagen deposition, extracellular matrix (ECM) protein production following injury. Pharmacological inhibition RU.521 reduced suppressed attenuated Mechanistically, double‐stranded released from damaged cells, induces inflammatory responses. Conclusions Implications Our study identifies pathway as critical regulator activation Therefore, may represent novel therapeutic strategy for CKD.

Language: Английский

Citations

3
Role of mitochondria in pathogenesis and therapy of renal fibrosis DOI
Xiaodong Zhao, Yunkuo Li, Jinyu Yu

et al.

Metabolism, Journal Year: 2024, Volume and Issue: 155, P. 155913 - 155913

Published: April 11, 2024

Language: Английский

Citations

15
The role of non-protein-coding RNAs in ischemic acute kidney injury DOI Creative Commons
Fatemeh Sabet Sarvestani, Afsoon Afshari, Negar Azarpira

et al.

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

Published: Feb. 8, 2024

Acute kidney injury (AKI) is a condition characterized by rapid decline in function within span of 48 hours. It influenced various factors including inflammation, oxidative stress, excessive calcium levels cells, activation the renin-angiotensin system, and dysfunction microcirculation. Ischemia-reperfusion (IRI) recognized as major cause AKI; however, precise mechanisms behind this process are not yet fully understood effective treatments still needed. To enhance accuracy diagnosing AKI during its early stages, utilization innovative markers crucial. Numerous studies suggest that certain noncoding RNAs (ncRNAs), such long (lncRNAs), microRNAs (miRNAs), circular (circRNAs), play central role regulating gene expression protein synthesis. These ncRNAs closely associated with development recovery have been detected both tissue bodily fluids. Furthermore, specific may serve diagnostic potential targets for therapeutic interventions AKI. This review aims to summarize functional roles changes observed ischemic AKI, well explore their potential.

Language: Английский

Citations

4
Iron management and exercise training in individuals with chronic kidney disease: lived experiences DOI Creative Commons
Courtney J. Lightfoot, Sharlene A. Greenwood, Elham Asgari

et al.

Clinical Kidney Journal, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 1, 2025

ABSTRACT Background Non-anaemic iron deficiency is highly prevalent in people living with chronic kidney disease (CKD) but underdiagnosed and undertreated, especially earlier stages of CKD. A multicentre trial assessing the effect intravenous supplementation iron-deficiency not anaemic CKD included a qualitative sub-study that aimed to explore patient experience psychosocial impact deficiency, therapeutic intervention (intravenous exercise). Methods Semi-structured interviews were conducted 23 participants blinded treatment. Topics explored experiences symptoms, social leisure activities, quality life, participants’ views receiving intervention. Thematic analysis was used identify report themes. Results Six overarching themes identified: lack awareness deficiency; overwhelming feelings tiredness; feeling limited; balancing emotions; perceptions treatment received; participation on life participation. Trial participation, specifically exercise training, perceived be beneficial, improvements psychological wellbeing experienced. However, there no clear differences between groups, mixed about which received. Conclusions The tiredness individuals profound can result reduced vitality, impaired ability engage activities emotional conflict. Improved communication support management particularly fatigue, for may required, alongside effective interventions, improve symptom life.

Language: Английский

Citations

0
Baicalin: a potential therapeutic agent for acute kidney injury and renal fibrosis DOI Creative Commons
Xiaoming Li, Rui‐Hua Xu, Dan Zhang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

Acute kidney injury (AKI) is a common critical clinical disease that linked to significant morbidity, recurrence, and mortality. It characterized by fast prolonged loss in renal function arising from numerous etiologies pathogenic pathways. Renal fibrosis, defined as the excessive accumulation of collagen proliferation fibroblasts within tissues, contributes structural damage functional decline kidneys, playing pivotal role advancement Chronic Kidney Disease (CKD). Until now, while continuous replacement therapy (CRRT) has been utilized management severe AKI, there remains dearth effective targeted therapies for AKI stemming diverse etiologies. Similarly, identification specific biomarkers pharmacological targets treatment fibrosis challenge. Baicalin, naturally occurring compound classified flavonoid group commonly found Chinese herb Scutellaria baicalensis, shown range characteristics, such antioxidant, anti-inflammatory, antifibrotic, antitumor antiviral effects, evidenced research studies. Research shows Baicalin potential treating diseases like fibrosis. This review aims summarize Baicalin’s progress these areas, including its molecular mechanism, application treatment, absorption, distribution, metabolism, excretion. therapeutic effects are achieved through various pathways, antifibrosis, regulation apoptosis cell proliferation. Besides, we also hope this may give some enlightenment practice.

Language: Английский

Citations

0
The Anti-Neuroinflammatory Effects of Cepharanthine in Uric Acid-Induced Neuroinflammation DOI

Wenyan Guo,

Yi Yang, Guangyuan Liu

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119409 - 119409

Published: Jan. 1, 2025

Language: Английский

Citations

0
Epigenetic regulation of transcription factors involved in NLRP3 inflammasome and NF-kB signaling pathways DOI Creative Commons

John Kaszycki,

Minji Kim

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 19, 2025

The NLRP3 inflammasome and NF-κB signaling pathways play crucial roles in orchestrating inflammation immune defense.​ This review explores the intricate relationship between these epigenetic regulation, a field of growing importance understanding responses. Epigenetic modifications, including DNA methylation, histone non-coding RNAs (ncRNAs), significantly influence activity genes involved pathways, thereby modulating inflammatory provides comprehensive overview current research on how mechanisms interact with regulate pathways. It delves into advanced concepts such as RNA modifications 3D genome organization, their impact regulation. Furthermore, implications findings for developing novel therapeutic strategies targeting regulators diseases are discussed. By synthesizing recent advancements this rapidly evolving field, underscores critical role regulation highlights potential epigenetic-based therapies treating wide range conditions, autoimmune disorders cancer.

Language: Английский

Citations

0
Identification of druggable targets in acute kidney injury by proteome- and transcriptome-wide Mendelian randomization and bioinformatics analysis DOI Creative Commons
Jiachen Liu, Dongfeng Zeng, Yinhuai Wang

et al.

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 27, 2025

Acute kidney injury (AKI) remains a critical condition with limited therapeutic options, predominantly managed by renal replacement therapy. The challenge of developing targeted treatments persists. We integrated genetic data related to druggable proteins and gene expression AKI genome-wide association study (GWAS) findings. Based on multi-omics Mendelian randomization (MR), we identified the potential causal influence 5,883 unique genes AKI. also performed using reverse MR external cohort-based analysis verify robustness this relationship. Expression patterns these targets were examined bulk transcriptome single-cell data. In addition, drug repurposing analyses conducted explore existing medications. constructed molecular interaction network interplay between known drugs. Genetically predicted levels seven twelve associated an increased risk Of these, six (NCF1, TNFRSF1B, APEH, ACADSB, ADD1, FAM3B) prioritized based robust evidence validated in independent cohorts. Reverse showed one-way relationship targets. These are expressed proximal tubular cells, endothelial collecting duct-principal immune cells within both AKI-affected normal tissues. Several promising opportunities identified, such as telmisartan-NCF1, calcitriol-ACADSB, ethinyl estradiol-ACADSB. mapping pathway integration provided further insights, suggesting strategies for combinatorial therapies. This extensive investigation several highlighted repurposing. findings offer valuable insights that could shape future research development treatments.

Language: Английский

Citations

0
The role of N6-methyladenosine (m6A) in kidney diseases DOI Creative Commons

Luling You,

Zhongyu Han, Hao Chen

et al.

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Sept. 28, 2023

Chemical modifications are a specific and efficient way to regulate the function of biological macromolecules. Among them, RNA molecules exhibit variety that play important regulatory roles in various processes. More than 170 have been identified molecules, among which most common internal include N6-methyladenine (m 6 A), n1-methyladenosine 1 5-methylcytosine 5 C), 7-methylguanine nucleotide 7 G). The widely affected modification is m A, whose writers, readers, erasers all effects on localization, splicing, translation, degradation. These functions, turn, affect functionality disease development. modifications, especially unique role renal cell carcinoma disease. In this manuscript, we will focus m6A diseases such as acute kidney injury, chronic disease, lupus nephritis, diabetic cancer.

Language: Английский

Citations

9