Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Redox-Mediated Artificial Non-Enzymatic Antioxidant MXene Nanoplatforms for Acute Kidney Injury Alleviation.

ABSTRACT: Acute kidney injury (AKI), as a common oxidative stress-related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID-19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology-mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme-mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non-specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non-enzymatic antioxidant strategy based on ultrathin Ti₃ C₂ -PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS-triggered biodegradability and broad-spectrum ROS scavenging ability through the readily occurring redox reaction between Ti₃ C₂ and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress-induced inflammatory response through inhibition of NF-κB signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox-mediated non-enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS-associated diseases.

SUBMITTER: Zhao X

PROVIDER: S-EPMC8456282 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Mitochondrial Targeted Antioxidant SKQ1 Ameliorates Acute Kidney Injury by Inhibiting Ferroptosis.

Project description:Emerging evidence suggests that ferroptosis is highly correlated with the pathogenesis of acute kidney injury (AKI). Ferroptosis, an iron-dependent form of cell death, is manifested by a toxic accumulation of lipid peroxides and ultrastructural changes in mitochondria. We herein investigated the effect of Visomitin (SKQ1), a novel mitochondria-targeting antioxidant, on several AKI models in vivo and in vitro. Our results revealed that SKQ1 treatment greatly reversed renal outcomes in cisplatin, ischemia-reperfusion injury (IRI), or folic acid-induced AKI models. These effects were reflected in attenuated levels of renal injury biomarkers, histologic indices of tubular injury, and inflammatory infiltration in the SKQ1-treated groups. Transcriptomics analysis depicted ferroptosis signaling as the most pronounced pathway downregulated after SKQ1 treatment. Consequently, administration of SKQ1 significantly ameliorated lipid peroxide accumulation and inhibited ferroptosis in the kidneys of mice with AKI. In cultured human proximal tubule epithelial cells (HK2), SKQ1 treatment markedly mitigated cisplatin-induced mitochondrial reactive oxygen species (ROS) production, resulting in lower levels of lipid peroxidation and ferroptosis. In conclusion, SKQ1 treatment protected against ischemic- or nephrotoxic-induced AKI by inhibiting ferroptosis in vivo and in vitro. These results could facilitate a broader understanding of the interaction between mitochondrial antioxidants and ferroptotic defense mechanisms, providing a possible therapeutic strategy in AKI.

| S-EPMC9526623 | biostudies-literature

Integrated Analysis of m6A Methylome in Cisplatin-Induced Acute Kidney Injury and Berberine Alleviation in Mouse.

Project description:BackgroundN6-methyladenosine (m6A) is the most abundant modification known in mRNAs. It participates in a variety of physiological and pathological processes, such as metabolism, inflammation, and apoptosis.AimsTo explore the mechanism of m6A in cisplatin-induced acute kidney injury (AKI) and berberine alleviation in mouse.MethodsThis study investigated the N6-methyladenosine (m6A) methylome of kidneys from three mouse groups: C57 mice (controls), those with CI-AKI (injury group, IG), and those pretreated with berberine (treatment group, TG). Methylated RNA Immunoprecipitation Next Generation Sequencing (MeRIP-seq) and RNA-seq were performed to identify the differences between the injury group and the control group (IvC) and between the treatment group and the injury group (TvI). Western blotting was performed to identify the protein levels of candidate genes.ResultsIn IvC, differentially methylated genes (DMGs) were enriched in metabolic processes and cell death. In TvI, DMGs were enriched in tissue development. Several genes involved in important pathways related to CI-AKI showed opposite methylation and expression trends in the IvC and TvI comparisons.Conclusionm6A plays an important role in cisplatin induced AKI and berberine may alleviate this process.

| S-EPMC7718005 | biostudies-literature

A MXene-derived redox homeostasis regulator perturbs the Nrf2 antioxidant program for reinforced sonodynamic therapy.

Project description:Ultrasound (US)-mediated sonodynamic therapy (SDT) has emerged as a spatiotemporally controllable therapeutic modality in combating cancer because of its high tissue-penetration depth and minimal invasiveness. However, the elevated nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant program in cancer cells can serve as a chief reactive oxygen species (ROS) detoxification system to alleviate oxidative injury and promote tumorigenesis, and thus greatly antagonize the therapeutic efficacy of ROS-mediated anticancer therapies. Herein, we report that vanadium carbide MXene-derived carbon dots (PMQDs) can act as high-efficacy sonosensitizers to efficiently generate ROS upon US irradiation and simultaneously hinder the Nrf2 antioxidant program for enhanced sonodynamic therapy of cancer. These PMQDs show superior US-triggered ROS generating ability because of their efficient migration/separation of electron-hole pairs and narrow bandgap. Importantly, these PMQDs can serve as efficient redox homeostasis regulators to perturb the Nrf2 antioxidant mechanism and thus reduce its effects on ROS neutralization for enhanced SDT efficacy. Overall, the present study will not only provide a new paradigm to augment SDT by perturbing the Nrf2 antioxidant program, but also give valuable insights into developing high-efficacy MXene-derived nanoagents for cancer therapy.

| S-EPMC9172572 | biostudies-literature

Artificial intelligence algorithms permits rapid acute kidney injury risk classification of patients with acute myocardial infarction.

Project description:ObjectiveThis study aimed to develop and validate several artificial intelligence (AI) models to identify acute myocardial infarction (AMI) patients at an increased risk of acute kidney injury (AKI) during hospitalization.MethodsIncluded were patients diagnosed with AMI from the Medical Information Mart for Intensive Care (MIMIC) III and IV databases. Two cohorts of AMI patients from Changzhou Second People's Hospital and Xuzhou Center Hospital were used for external validation of the models. Patients' demographics, vital signs, clinical characteristics, laboratory results, and therapeutic measures were extracted. Totally, 12 AI models were developed. The area under the receiver operating characteristic curve (AUC) were calculated and compared.ResultsAKI occurred during hospitalization in 1098 (28.3 %) of the 3882 final enrolled patients, split into training (3105) and test (777) sets randomly. Among them, Random Forest (RF), C5.0 and Bagged CART models outperformed the other models in both the training and test sets. The AUCs for the test set were 0.754, 0.734 and 0.730, respectively. The incidence of AKI was 9.8 % and 9.5 % in 2202 patients in the Changzhou cohort and 807 patients in the Xuzhou cohort with AMI, respectively. The AUCs for patients in the Changzhou cohort were RF, 0.761; C5.0, 0.733; and bagged CART, 0.725, respectively, and Xuzhou cohort were RF, 0.799; C5.0, 0.808; and bagged CART, 0.784, respectively.ConclusionSeveral machines learning-based prediction models for AKI after AMI were developed and validated. The RF, C5.0 and Bagged CART model performed robustly in identifying high-risk patients earlier.Clinical trial approval statementThis Trial was registered in the Chinese clinical trials registry: ChiCTR1800014583. Registered January 22, 2018 (http://www.chictr.org.cn/searchproj.aspx).

| S-EPMC11367145 | biostudies-literature

A Novel Antioxidant Protects Against Contrast Medium-Induced Acute Kidney Injury in Rats.

Project description:Many studies proposed that oxidative stress and apoptosis are key mechanisms in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). Xylose-pyrogallol conjugate (XP) is an original effective antioxidant that showed decent antioxidant and anti-apoptosis effect before. Thus the therapeutic effect and mechanism of XP in preventing CI-AKI in the short and long term were investigated in this research. Renal function and histological grade were evaluated to determine the severity of renal injury. Kidney samples were then collected for the measurement of oxidative stress markers and the detection of apoptosis. Transmission electron microscopy (TEM) and western blot of mitochondrial protein were utilized for the analysis of the mitochondrial conditions. The results demonstrated that the CI-AKI rats caused a significant decrease in renal function accompanied by a remarkable increase in Malondialdehyde (MDA), bax, caspase-3, cytochrome c (Cyt C) level, TdT-mediated dUTP nick end labeling (TUNEL) positive apoptotic cells, and damaged mitochondria, while a decline in antioxidase activities and mitochondrial superoxide dismutase 2 (SOD2) expression compared with the control rats. However, when XP (50 or 100 or 200 mg/kg/day) was given orally for consecutive 7 days before CI-AKI modeling, XP (200 mg/kg) showed a better capability to restore renal dysfunction, histopathological appearance, the level of apoptosis, mitochondrial damage, oxidative stress, and fibrosis generation without interference in computed tomographic imaging. Our study indicated that antioxidant XP played a nephroprotective role probably via antiapoptotic and antioxidant mechanisms. Besides, XP may regulate the mitochondria pathway via decreasing the ratio of bax/bcl-2, inhibiting caspase-3 expression, cytochrome c release, and superoxide dismutase 2 activity. Overall, XP as a high-efficient antioxidant may have the potentials to prevent CI-AKI.

| S-EPMC7729082 | biostudies-literature

Mitochondrial Damage and Mitochondria-Targeted Antioxidant Protection in LPS-Induced Acute Kidney Injury.

Project description:Induced and frequently unwanted alterations in the mitochondrial structure and functions are a key component of the pathological cascade in many kidney pathologies, including those associated with acute damage. One of the principal pathogenic elements causing mitochondrial dysfunction in Acute Kidney Injury (AKI) is oxidative stress. After ischemia and nephrotoxic action of drugs, sepsis and systemic inflammation are the most frequent causes of AKI. As the kidney suffers from oxidative stress during sepsis, one of the most promising approaches to alleviate such damaging consequences is the use of antioxidants. Considering administration of lipopolysaccharide (LPS) as a model of sepsis, we demonstrate that the mitochondria of neonatal renal tissue are severely affected by LPS-induced AKI, with pathological ultrastructural changes observed in both the mitochondria of the renal tubular epithelium and the vascular endothelium. Upon mitochondrial damage, we evaluated the effect of the mitochondria-targeted antioxidant plastoquinol decylrhodamine 19 (SkQR1) on the development of acute renal failure in newborn rats associated with systemic inflammation induced by the administration of LPS. We found that SkQR1 administration 3 h before LPS led to decreased urinal expression of the AKI marker neutrophil gelatinase-associated lipocalin 2 (NGAL), in addition to a decrease in urea and creatinine levels in the blood. Additionally, an observed impairment of proliferative activity in the neonatal kidney caused by LPS treatment was also prevented by the treatment of rat pups with SkQR1. Thus, one of the key events for renal tissue damage in neonatal sepsis is an alteration in the structure and function of the mitochondria and the mitochondria-targeted antioxidant SkQR1 is an effective nephroprotective agent, which protects the neonatal kidney from sepsis-induced AKI.

| S-EPMC6617298 | biostudies-literature

Cross-site transportability of an explainable artificial intelligence model for acute kidney injury prediction.

Project description:Artificial intelligence (AI) has demonstrated promise in predicting acute kidney injury (AKI), however, clinical adoption of these models requires interpretability and transportability. Non-interoperable data across hospitals is a major barrier to model transportability. Here, we leverage the US PCORnet platform to develop an AKI prediction model and assess its transportability across six independent health systems. Our work demonstrates that cross-site performance deterioration is likely and reveals heterogeneity of risk factors across populations to be the cause. Therefore, no matter how accurate an AI model is trained at the source hospital, whether it can be adopted at target hospitals is an unanswered question. To fill the research gap, we derive a method to predict the transportability of AI models which can accelerate the adaptation process of external AI models in hospitals.

| S-EPMC7653032 | biostudies-literature

A Melanin-Based Natural Antioxidant Defense Nanosystem for Theranostic Application in Acute Kidney Injury.

Project description:Acute kidney injury (AKI) is frequently associated with oxidative stress and causes high mortality annually in clinics. Nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for the treatment of AKI. Herein, a novel biomedical use of the endogenous biopolymer melanin as a theranostic natural antioxidant defense nanoplatform for AKI is reported. In this study, ultrasmall Mn2+-chelated melanin (MMP) nanoparticles are easily prepared via a simple coordination and self-assembly strategy, and further incorporated with polyethylene glycol (MMPP). In vitro experiments reveal the ability of MMPP nanoparticles to scavenge multiple toxic reactive oxygen species (ROS) and suppress ROS-induced oxidative stress. Additionally, in vivo results from a murine AKI model demonstrate preferential renal uptake of MMPP nanoparticles and a subsequent robust antioxidative response with negligible side effects according to positron emission tomography/magnetic resonance (PET/MR) bimodal imaging and treatment assessment. These results indicate that the effectiveness of MMPP nanoparticles for treating AKI suggests the potential efficacy of melanin as a natural theranostic antioxidant nanoplatform for AKI, as well as other ROS-related diseases.

| S-EPMC7017599 | biostudies-literature

Antioxidant therapies for acute spinal cord injury.

Project description:One of the most investigated molecular mechanisms involved in the secondary pathophysiology of acute spinal cord injury (SCI) is free radical-induced, iron-catalyzed lipid peroxidation (LP) and protein oxidative/nitrative damage to spinal neurons, glia, and microvascular cells. The reactive nitrogen species peroxynitrite and its highly reactive free radicals are key initiators of LP and protein nitration in the injured spinal cord, the biochemistry, and pathophysiology of which are first of all reviewed in this article. This is followed by a presentation of the antioxidant mechanistic approaches and pharmacological compounds that have been shown to have neuroprotective properties in preclinical SCI models. Two of these, which act by inhibition of LP, are high-dose treatment with the glucocorticoid steroid methylprednisolone (MP) and the nonglucocorticoid 21-aminosteroid tirilazad, have been demonstrated in the multicenter NASCIS clinical trials to produce at least a modest improvement in neurological recovery when administered within the first 8 hours after SCI. Although these results have provided considerable validation of oxidative damage as a clinically practical neuroprotective target, there is a need for the discovery of safer and more effective antioxidant compounds for acute SCI.

| S-EPMC3101837 | biostudies-other

Does Artificial Intelligence Make Clinical Decision Better? A Review of Artificial Intelligence and Machine Learning in Acute Kidney Injury Prediction.

Project description:Acute kidney injury (AKI) is a common complication of hospitalization that greatly and negatively affects the short-term and long-term outcomes of patients. Current guidelines use serum creatinine level and urine output rate for defining AKI and as the staging criteria of AKI. However, because they are not sensitive or specific markers of AKI, clinicians find it difficult to predict the occurrence of AKI and prescribe timely treatment. Advances in computing technology have led to the recent use of machine learning and artificial intelligence in AKI prediction, recent research reported that by using electronic health records (EHR) the AKI prediction via machine-learning models can reach AUROC over 0.80, in some studies even reach 0.93. Our review begins with the background and history of the definition of AKI, and the evolution of AKI risk factors and prediction models is also appraised. Then, we summarize the current evidence regarding the application of e-alert systems and machine-learning models in AKI prediction.

| S-EPMC8701097 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data