Ischemia–Reperfusion Injury in Kidney Transplantation: Mechanisms and Potential Therapeutic Targets DOI Open Access
Francesco Lasorsa,

Monica Rutigliano,

Martina Milella

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4332 - 4332

Published: April 14, 2024

Kidney transplantation offers a longer life expectancy and better quality of than dialysis to patients with end-stage kidney disease. Ischemia–reperfusion injury (IRI) is thought be cornerstone in delayed or reduced graft function increases the risk rejection by triggering immunogenicity organ. IRI an unavoidable event that happens when blood supply temporarily then restored result several biological pathways, such as transcriptional reprogramming, apoptosis necrosis, innate adaptive immune responses, endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) β-oxidation for energy production since more ATP molecules are yielded per substrate molecule glucose oxidation. Upon ischemia–reperfusion damage, system activates achieve tissue clearance repair. Several cells, cytokines, enzymes, receptors, ligands known take part these events. The complement cascade might start even before organ procurement deceased donors. However, additional experimental clinical data required understand pathogenic events place during this complex process.

Language: Английский

Ferroptosis in Parkinson's disease: Molecular mechanisms and therapeutic potential DOI

Xv-shen Ding,

Li Gao, Han Zheng

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102077 - 102077

Published: Sept. 24, 2023

Language: Английский

Citations

82
Mitochondrial quality control in human health and disease DOI Creative Commons
Bohao Liu,

Chen-Zhen Xu,

Yi Liu

et al.

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: May 29, 2024

Abstract Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable vital life processes such cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key like biogenesis, dynamics, mitophagy, which have garnered increasing attention from researchers unveil specific molecular mechanisms. this review, we present comprehensive summary of primary mechanisms functions regulators involved major components MQC. Furthermore, critical regulated by MQC its diverse roles progression systemic diseases been described detail. We discuss agonists antagonists targeting MQC, aiming explore potential therapeutic research prospects enhancing stabilize function.

Language: Английский

Citations

41
Mitochondrial metabolism and targeted treatment strategies in ischemic-induced acute kidney injury DOI Creative Commons
Yongming Chen, Zixian Li, Hongyong Zhang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 10, 2024

Ischemia-reperfusion injury (IRI) is a common cause of acute kidney (AKI). The susceptible to IRI under several clinical conditions, including hypotension, sepsis, and surgical procedures, such as partial nephrectomy transplantation. Extensive research has been conducted on the mechanism intervention strategies renal in past decades; however, complex pathophysiology IRI-induced AKI (IRI-AKI) not fully understood, there remains lack effective treatments for AKI. Renal involves processes, reactive oxygen species (ROS) production, inflammation, apoptosis. Mitochondria, centers energy metabolism, are increasingly recognized substantial contributors early phases IRI. Multiple mitochondrial lesions have observed tubular epithelial cells (TECs) IRI-AKI mice, damaged or dysfunctional mitochondria toxic because they produce ROS release cell death factors, resulting TEC In this review, we summarize recent advances pathology ischemic highlight promising therapeutic approaches targeting dysfunction prevent treat human

Language: Английский

Citations

26
Cardiovascular disease: Mitochondrial dynamics and mitophagy crosstalk mechanisms with novel programmed cell death and macrophage polarisation DOI Creative Commons
Dandan Liu,

Hewei Qin,

Yang Gao

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107258 - 107258

Published: June 21, 2024

Several cardiovascular illnesses are associated with aberrant activation of cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage polarisation as hallmarks contributing to vascular damage abnormal cardiac function. Meanwhile, these three novel forms dysfunction closely related mitochondrial homeostasis. Mitochondria the main organelles that supply energy maintain Mitochondrial stability is maintained through a series regulatory pathways, such fission, fusion mitophagy. Studies have shown (e.g., impaired dynamics mitophagy) promotes ROS production, leading oxidative stress, which induces M1 phenotypic polarisation. Therefore, an in-depth knowledge dynamic regulation mitochondria during necessary understand disease development. This paper systematically summarises impact changes in mitophagy on regulating dysfunctions promote understanding pathogenesis diseases provide corresponding theoretical references for treating diseases.

Language: Английский

Citations

23
Electroacupuncture attenuates ferroptosis by promoting Nrf2 nuclear translocation and activating Nrf2/SLC7A11/GPX4 pathway in ischemic stroke DOI Creative Commons

Xichen Yang,

Ying Jin,

Rong Ning

et al.

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

Published: Jan. 4, 2025

Abstract Objective Electroacupuncture has been shown to play a neuroprotective role following ischemic stroke, but the underlying mechanism remains poorly understood. Ferroptosis key in injury process. In present study, we wanted explore whether electroacupuncture could inhibit ferroptosis by promoting nuclear factor erythroid-2-related 2 (Nrf2) translocation. Methods The stroke model was established middle cerebral artery occlusion/reperfusion (MCAO/R) adult rats. These rats have randomly divided into EA + MCAO/R group, Brusatol group (the inhibitor of Nrf2), and DMSO Sham group. received intervention 24 h after modeling for 7 consecutive days. behavioral function evaluated Neurologic severity score (NSS), Garcia score, Foot-fault Test, Rotarod Test. infarct volume detected TTC staining, neuronal damage observed Nissl staining. levels Fe 2+ , reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) were measured ELISA. immunofluorescence Western blotting used detect expression Total Nrf2, p-Nrf2, Nuclear Cytoplasmic essential proteins, including glutathione peroxidase 4 (GPX4), solute carrier family member 11 (SLC7A11) ferritin heavy chain 1 (FTH1). mitochondria transmission electron microscopy (TEM). Results improved neurological deficits MCAO/R, decreased brain volume, alleviated damage, inhibited ROS, MDA accumulation, increased SOD levels, GPX4, SLC7A11 FTH1, rescued injured mitochondria. Especially, found that up-regulated promoted phosphorylation Nrf2 translocation, However, reversed effect electroacupuncture. Conclusion can alleviate I/R injury-induced It is expected these data will provide novel insights mechanisms protecting against potential targets stroke. Graphical

Language: Английский

Citations

3
Isovitexin targets SIRT3 to prevent steroid-induced osteonecrosis of the femoral head by modulating mitophagy-mediated ferroptosis DOI Creative Commons

Yinuo Fan,

Zhiwen Chen, Haixing Wang

et al.

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 26, 2025

Abstract The death of osteoblasts induced by glucocorticoid (GC)-mediated oxidative stress plays a crucial role in the development steroid-induced osteonecrosis femoral head (SIONFH). Improving bone formation driven has shown promising outcomes prognosis SIONFH. Isovitexin demonstrated antioxidant properties, but its therapeutic effects on GC-induced and SIONFH remain unexplored. In this study, we analyzed clinical samples obtained from patients using proteomic bioinformatic approaches. We found an imbalance mitochondrial homeostasis ferroptosis-induced impairment osteogenic capacity Subsequently, investigated cause-and-effect relationship between mitochondria ferroptosis, as well regulatory mitophagy maintaining controlling ferroptosis. then identified critical involvement SIRT3 modulating Furthermore, molecular docking co-immunoprecipitation confirmed strong interaction BNIP3. Strikingly, restoring expression significantly inhibited pathological mediated BNIP3/NIX pathway. Additionally, discovered that Isovitexin, promoting expression, effectively regulated mitophagy, preserved osteoblasts, suppressed restored capacity, leading to remarkable improvements These findings reveal mechanisms highlight potential targeting strategy suppress mitophagy-mediated ferroptosis against

Language: Английский

Citations

3
Metal‐Based Nanozymes with Multienzyme‐Like Activities as Therapeutic Candidates: Applications, Mechanisms, and Optimization Strategy DOI
Dan Li, Danni Dai,

Gege Xiong

et al.

Small, Journal Year: 2022, Volume and Issue: 19(7)

Published: Dec. 13, 2022

Most nanozymes in development for medical applications only exhibit single-enzyme-like activity, and are thus limited by insufficient catalytic activity dysfunctionality complex pathological microenvironments. To overcome the impediments of substrate availabilities concentrations, some metal-based may mimic two or more activities natural enzymes to catalyze cascade reactions multiple substrates simultaneously, thereby amplifying catalysis. Metal-based with multienzyme-like (MNMs) adapt dissimilar conditions exert different enzyme-like effects. These can synergize realize "self-provision substrate," which upstream catalysts produce downstream limitation microenvironment. Consequently, MNMs potent antitumor, antibacterial, anti-inflammatory effects preclinical models. This review summarizes cellular underlying mechanisms MNMs. Their potential utility optimization strategy from perspective clinical requirements also discussed, aim provide a theoretical reference design, development, therapeutic application their

Language: Английский

Citations

58
Broadening horizons: the multifaceted functions of ferroptosis in kidney diseases DOI Creative Commons
Qi Feng, Yang Yang, Kaidi Ren

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(12), P. 3726 - 3743

Published: Jan. 1, 2023

Ferroptosis is an iron-dependent programmed cell death pattern that characterized by iron overload, reactive oxygen species (ROS) accumulation and lipid peroxidation. Growing viewpoints support the imbalance of homeostasis disturbance metabolism contribute to tissue or organ injury in various kidney diseases triggering ferroptosis. At present, key regulators complicated network mechanisms associated with ferroptosis have been deeply studied; however, its role initiation progression has not fully revealed. Herein, we aim discuss features, ferroptosis, explore emerging roles organelles gather pharmacological progress, systematically summarize most recent discoveries about crosstalk between diseases, including renal carcinoma (RCC), acute (AKI), diabetic disease (DKD), autosomal dominant polycystic (ADPKD), fibrosis, lupus nephritis (LN) IgA nephropathy. We further conclude potential therapeutic strategies targeting for prevention treatment hope this work will provide insight study pathogenesis kidney-related diseases.

Language: Английский

Citations

37
Multi‐Functional Carbon Dots for Visualizing and Modulating ROS‐Induced Mitophagy in Living Cells DOI
Hao Li,

Jiaqing Guo,

Aikun Liu

et al.

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(17)

Published: Jan. 29, 2023

Abstract Reactive oxygen species (ROS)‐induced mitophagy is associated with a variety of diseases. Therefore, visualizing and modulating the process ROS‐induced essential for understanding role in cellular homeostasis, physiological processes, pathogenesis. Herein, using fluorescence lifetime imaging microscopy (FLIM), first time complete dynamic PINK1/Parkin pathway‐mediated described. Induced by photo‐controlled release ROS, nitrogen‐doped multi‐functional carbon nanozymes (ENZ‐NCDs) used as probe to visualize quantitatively study mitophagy. The successful preparation ENZ‐NCDs provides potentially powerful tool new strategy real‐time monitoring future quantification mitochondrial damage caused ROS mitophagy‐related

Language: Английский

Citations

34
4-Octyl itaconate attenuates LPS-induced acute kidney injury by activating Nrf2 and inhibiting STAT3 signaling DOI Creative Commons

Lujun Xu,

Juan Cai, Chenrui Li

et al.

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: April 24, 2023

Abstract Background Septic acute kidney injury (S-AKI) is the leading form of failure among hospitalized patients, and inflammatory response involved in this process. 4-octyl itaconate (4-OI) a multi-target derivative with potent anti-inflammatory action. However, it remains elusive whether how 4-OI contributes to regulation S-AKI. Methods We employed lipopolysaccharide (LPS)-induced AKI murine model explored potential renoprotective effect vivo . In vitro experiments, BUMPT cells, renal tubular cell line, were conducted examine effects on inflammation, oxidative stress, mitophagy. Moreover, STAT3 plasmid was transfected cells investigate role signaling 4-OI-administrated state. Results demonstrate that protects against S-AKI through suppressing inflammation stress enhancing significantly reduced levels Scr, BUN, Ngal as well LPS-induced mice. restrained by reducing macrophage infiltration expression IL-1β NLRP3 septic kidney. also ROS levels, cleaved caspase-3 boosted antioxidants such HO-1, NQO1 addition, treatment promoted Mechanistically, activated Nrf2 suppressed phosphorylated vitro. Molecular docking revealed binding affinity towards STAT3. ML385, specific inhibitor, partially repressed anti-oxidative restricted mitophagy induced Transfected provoked Conclusion These data suggest ameliorates overactivation pathway, inactivation Our study identifies promising pharmacologic for

Language: Английский

Citations

34