Regulated cell death pathways in kidney disease

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 19(5), P. 281 - 299

Published: March 23, 2023

Language: Английский

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Typhaneoside-Tetrahedral Framework Nucleic Acids System: Mitochondrial Recovery and Antioxidation for Acute Kidney Injury treatment

ACS Nano, Journal Year: 2023, Volume and Issue: 17(9), P. 8767 - 8781

Published: April 14, 2023

Acute kidney injury (AKI) is not only a worldwide problem with cruel hospital mortality rate but also an independent risk factor for chronic disease and promoting its progression. Despite supportive therapeutic measures, there no effective treatment AKI. This study employs tetrahedral framework nucleic acid (tFNA) as vehicle combines typhaneoside (Typ) to develop the tFNA-Typ complex (TTC) treating With precise targeting ability on mitochondria renal tubule, increased antiapoptotic antioxidative effect, promoted function restoration, TTC represents promising nanomedicine AKI treatment. Overall, this has developed dual-targeted nanoparticle enhanced effects could have critical clinical applications in future.

Language: Английский

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Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance

Advanced Science, Journal Year: 2023, Volume and Issue: 10(26)

Published: July 12, 2023

In recent years, the incidence of gastrointestinal cancers is increasing, particularly in younger population. Effective treatment crucial for improving patients' survival outcomes. Programmed cell death, regulated by various genes, plays a fundamental role growth and development organisms. It also critical maintaining tissue organ homeostasis takes part multiple pathological processes. addition to apoptosis, there are other types programmed such as ferroptosis, necroptosis, pyroptosis, which can induce severe inflammatory responses. Notably, besides pyroptosis contribute occurrence cancers. This review aims provide comprehensive summary on biological roles molecular mechanisms well their regulators hope open up new paths tumor targeted therapy near future.

Language: Английский

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Mediators of necroptosis: from cell death to metabolic regulation

EMBO Molecular Medicine, Journal Year: 2024, Volume and Issue: 16(2), P. 219 - 237

Published: Jan. 9, 2024

Abstract Necroptosis, a programmed cell death mechanism distinct from apoptosis, has garnered attention for its role in various pathological conditions. While initially recognized involvement death, recent research revealed that key necroptotic mediators, including receptor-interacting protein kinases (RIPKs) and mixed lineage kinase domain-like (MLKL), possess additional functions go beyond inducing demise. These encompass influencing critical aspects of metabolic regulation, such as energy metabolism, glucose homeostasis, lipid metabolism. Dysregulated necroptosis been implicated diseases, obesity, diabetes, dysfunction-associated steatotic liver disease (MASLD) alcohol-associated (ALD), contributing to chronic inflammation tissue damage. This review provides insight into the multifaceted necroptosis, encompassing both these extra-necroptotic functions, context diseases. Understanding this intricate interplay is crucial developing targeted therapeutic strategies diseases currently lack effective treatments.

Language: Английский

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The emerging role of regulated cell death in ischemia and reperfusion-induced acute kidney injury: current evidence and future perspectives

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

Published: May 4, 2024

Abstract Renal ischemia‒reperfusion injury (IRI) is one of the main causes acute kidney (AKI), which a potentially life-threatening condition with high mortality rate. IRI complex process involving multiple underlying mechanisms and pathways cell dysfunction. Additionally, various types death have been linked to IRI, including necroptosis, apoptosis, pyroptosis, ferroptosis. These processes operate differently varying degrees in different patients, but each plays role pathological conditions AKI. Advances understanding pathophysiology will lead development new therapeutic approaches that hold promise for improving outcomes patients This review provides an overview recent research on molecular IRI-AKI, focus regulated (RCD) forms such as Overall, targeting RCD shows potential approach treating IRI-AKI.

Language: Английский

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Metformin potentiates nephrotoxicity by promoting NETosis in response to renal ferroptosis

Cell Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Oct. 17, 2023

Given the rapidly aging population, aging-related diseases are becoming an excessive burden on global healthcare system. Metformin has been shown to be beneficial many age-related disorders, as well increase lifespan in preclinical animal models. During process, kidney function progressively declines. Currently, whether and how metformin protects remains unclear. In this study, among longevity drugs, including metformin, nicotinamide, resveratrol, rapamycin, senolytics, we unexpectedly found that even at low doses, exacerbated experimentally-induced acute injury (AKI) increased mortality mice. By single-cell transcriptomics analysis, death of renal parenchymal cells together with expansion neutrophils occurs upon treatment after AKI. We identified programmed cell by ferroptosis blocking ferroptosis, or depleting against metformin-induced nephrotoxicity. Mechanistically, induction AKI, initiates migration site via surface receptor CXCR4-bound metformin-iron-NGAL complex, which results NETosis aggravated Finally, demonstrated reducing iron showed protective effects injury, supports notion plays important role metformin-triggered Taken together, these findings delineate a novel mechanism underlying metformin-aggravated nephropathy highlight mechanistic relationship between iron, resulting

Language: Английский

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Cell death pathways: molecular mechanisms and therapeutic targets for cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(9)

Published: Sept. 1, 2024

Abstract Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell can provide novel therapeutic strategies battling cancer. This review explores several key mechanisms apoptosis, necroptosis, autophagic death, ferroptosis, pyroptosis. The research gap addressed involves a thorough analysis how these be precisely targeted therapy, considering tumor heterogeneity adaptation. It delves into genetic epigenetic factors signaling cascades like phosphatidylinositol 3‐kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) mitogen‐activated protein kinase/extracellular signal‐regulated (MAPK/ERK) pathways, which are critical death. Additionally, interaction microenvironment with cells, particularly influence hypoxia, nutrient deprivation, immune cellular interactions, explored. Emphasizing strategies, this highlights emerging modulators inducers such as B lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, innovative approaches to induce ferroptosis provides insights therapy's future direction, focusing on multifaceted circumvent drug resistance. examination evolving underlines considerable clinical potential continuous necessity in‐depth exploration within scientific domain.

Language: Английский

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Noncoding RNAs in sepsis-associated acute liver injury: Roles, mechanisms, and therapeutic applications

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107596 - 107596

Published: Jan. 10, 2025

Sepsis is a life-threatening syndrome characterized by organ dysfunction caused dysregulated host response to infection. Sepsis-associated acute liver injury (SA-ALI) frequent and serious complication of sepsis that considerably impacts both short-term long-term survival outcomes. In intensive care units (ICUs), the mortality rate patients with SA-ALI remains high, mostly due absence effective early diagnostic markers suitable therapeutic strategies. Recent studies have demonstrated importance non-coding RNAs (ncRNAs) in development progression SA-ALI. This review focuses on critical roles ncRNAs, including microRNAs (miRNAs), long (lncRNAs), circular (circRNAs), regulating "cytokine storms", oxidative stress, mitochondrial dysfunction, programmed cell death SA-ALI, summarizes current state limitations existing lncRNAs circRNAs By integrating advancements high-throughput sequencing technologies, this provides novel insights into dual potential ncRNAs as biomarkers targets, offers new ideas for diagnosis treatment research highlights challenges clinical translation.

Language: Английский

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Emerging role of PANoptosis in kidney diseases: molecular mechanisms and therapeutic opportunities

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

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Carbon Dot Nanozymes with Ferrous Ion‐Chelating and Antioxidative Activity Inhibiting Ferroptosis to Alleviate Renal Ischemia‐Reperfusion Injury

Small, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Renal ischemia-reperfusion (I/R) significantly contributes to acute kidney injury (AKI), causing substantial oxidative stress and metabolic disruptions. Ferroptosis, a Fe2+-dependent form of regulated cell death characterized by lipid peroxide accumulation, is the predominant cause renal I/R (RIRI). Here, carbon dot (C-dot) nanozymes that inhibit ferroptosis regulating Fe2⁺ levels scavenging reactive oxygen species, offering potential treatment for RIRI are reported. C-dots chelate via surface carbonyl, hydroxyl, carboxyl groups reduce free levels, suppress Fenton reaction, limit hydroxyl radical generation. Additionally, scavenge superoxide anions radicals restore redox balance. By targeting kidneys, effectively iron overload peroxidation prevent ferroptotic in male mice model. RNA sequencing (RNA-seq) analysis further confirms crucial roles mitigating stress, preserving homeostasis, downregulating acyl-CoA synthetase long-chain family member 4 (ACSL4) after I/R. This work emphasizes perfect alignment between multifunctional conditions required inhibiting offers an innovative strategy treat effectively.

Language: Английский

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