Evaluating renal injury characteristics in different rat models of hyperuricemia and elucidating pathological molecular mechanisms via serum metabolomics DOI Creative Commons
Mengwen Liu, Jing Shen,

Xuanshi Chen

et al.

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

Published: Sept. 2, 2024

Hyperuricemia has emerged as a significant global health concern, closely associated with various metabolic disorders. The adverse effects frequently observed current pharmacological treatments for hyperuricemia highlight the urgent need reliable animal models to elucidate disease’s pathophysiological mechanisms, thereby facilitating development of safer and more effective therapies. In this study, we established three rat using potassium oxonate, either alone or in combination fructose adenine. Each model exhibited distinct pathological changes, fructose, adenine causing significantly severe damage liver kidney functions than oxonate alone. Serum metabolomics analyses revealed profound dysregulation pathways purine, pyrimidines, glutathione, underscoring pivotal role oxidative stress progression hyperuricemia. We identified key biomarkers such orotidine, ureidosuccinic acid, uracil, pseudouridine, which are uric acid-induced hepatic renal systems. MetOrigin tracing analysis further that differential metabolites related primarily involved host-microbiome co-metabolic pathways, particularly purine metabolism, bacterial phyla Pseudomonadota , Actinomycetota Ascomycota being linked critical processes acid production. These findings not only enhance our understanding pathogenic mechanisms underlying but also provide robust experimental foundation innovative treatment strategies.

Language: Английский

Peroxisomal hydrogen peroxide signaling: A new chapter in intracellular communication research DOI Open Access
Marc Fransen, Celien Lismont

Current Opinion in Chemical Biology, Journal Year: 2024, Volume and Issue: 78, P. 102426 - 102426

Published: Jan. 21, 2024

Language: Английский

Citations

13
Cuproptosis-Inducing Functional Nanocomposites for Enhanced and Synergistic Cancer Radiotherapy DOI

Tiaoyan Jiang,

Tian-Ying Jia,

Yipengchen Yin

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Radiotherapy is crucial in local cancer management and needs advancements. Tumor cells elevate intracellular copper levels to promote growth resist radiation; thus, targeted delivery mitochondria could enhance radiotherapy by inducing cuproptosis tumor cells. In this study, we engineered a multifunctional nanoliposome complex, termed Lipo-Ele@CuO2, which encapsulates both peroxide (CuO2) the chelator elesclomol, can Cu ions mitochondria. The Lipo-Ele@CuO2 complex induces mitochondria-mediated synergistically enhances efficacy of radiotherapy. CuO2 acts as donor exhibits inherent sensitivity acidic environments. Additionally, it depletes glutathione, thereby sensitizing cuproptosis. Leveraging its pH-responsive properties microenvironment, facilitate controlled release efficiently delivering at sites. combined vitro vivo studies demonstrate that Lipo-Ele@CuO2-based therapy significantly improves antitumor excellent safety profiles, effectively boosting effectiveness Furthermore, metabolomic transcriptomic analyses reveal combination precipitates significant alterations energy metabolism, notably repressing genes related iron-sulfur cluster assembly glycolysis, confirming induction This therapeutic strategy provides viable approach for addressing clinical resistance demonstrates translational potential.

Language: Английский

Citations

1
ABCC1 deficiency potentiated noise-induced hearing loss in mice by impairing cochlear antioxidant capacity DOI Creative Commons
Jing Liu, Yijiang Bai, Yong Feng

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 74, P. 103218 - 103218

Published: June 1, 2024

The ABCC1 gene belongs to the ATP-binding cassette membrane transporter superfamily, which plays a crucial role in efflux of various endogenous and exogenous substances. Mutations can result autosomal dominant hearing loss. However, specific roles auditory function are not fully understood. Through immunofluorescence, we found that was expressed microvascular endothelial cells (ECs) stria vascularis (StV) murine cochlea. Then, an Abcc1 knockout mouse model established by using CRISPR/Cas9 technology elucidate inner ear. ABR threshold did significantly differ between WT Abcc1-/- mice at any age studied. After noise exposure, thresholds were elevated. Interestingly, after 14 days largely returned pre-exposure levels but mice. Our subsequent experiments showed integrity StV compromised number outer hair ribbons decreased cochleae post-exposure. Besides, production ROS accumulation 4-HNE increased. Furthermore, ECs cultured these under glucose oxidase challenge. Notably, 30 U/L (GO) induced severe oxidative stress damage cells. Compared with cells, apoptotic rate elevated In addition, reduced GSH/GSSG ratio GO treatment. Taken together, more susceptible noise-induced loss, possibly because knockdown compromises GSH antioxidant system ECs. N-acetylcysteine (NAC) may protect against

Language: Английский

Citations

8
Ferroptosis: a potential bridge linking gut microbiota and chronic kidney disease DOI Creative Commons

Zi‐Hui Mao,

Zhong‐Xiuzi Gao, Shaokang Pan

et al.

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

Published: May 15, 2024

Abstract Ferroptosis is a novel form of lipid peroxidation-driven, iron-dependent programmed cell death. Various metabolic pathways, including those involved in and iron metabolism, contribute to ferroptosis regulation. The gut microbiota not only supplies nutrients energy the host, but also plays crucial role immune modulation balance. In this review, we explore pathways associated with impact on host metabolism. We subsequently summarize recent studies influence regulation by discuss potential mechanisms through which affects ferroptosis. Additionally, conduct bibliometric analysis relationship between context chronic kidney disease. This can provide new insights into current research status future microbiota.

Language: Английский

Citations

7
Genetic factors in the pathogenesis of cardio-oncology DOI Creative Commons

Yalong Qi,

Yuhan Wei, Lixi Li

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 5, 2024

In recent years, with advancements in medicine, the survival period of patients tumours has significantly increased. The adverse effects tumour treatment on patients, especially cardiac toxicity, have become increasingly prominent. elderly breast cancer, treatment-related cardiovascular toxicity surpassed cancer itself as leading cause death. Moreover, an increasing number novel antitumour drugs, such multitargeted agents, antibody‒drug conjugates (ADCs), and immunotherapies, been applied clinical practice. cardiotoxicity induced by these drugs more pronounced, to a complex diverse mechanism damage. risks unintended are increased high-dose anthracyclines, concurrent radiation, addition traditional risk factors smoking, hypertension, diabetes, hyperlipidaemia, obesity. However, do not fully explain why only subset individuals experience whereas others similar features not. Recent studies indicate that genetics play significant role susceptibility development from therapies. These genes involved drug metabolism, oxidative damage, dysfunction, other processes. emerging evidence suggests epigenetics also plays drug-induced toxicity. We conducted review focusing example help oncologists cardiologists better understand mechanisms genetic this review, we specifically address relationship between alterations including chemotherapy-related changes, targeted therapy-related immune changes. discuss epigenetic hope will improve stratification enable therapeutic interventions mitigate consequences life-saving treatments.

Language: Английский

Citations

7
Engineering Stimuli‐Responsive Materials for Precision Medicine DOI Creative Commons
Ruixuan Zheng, Yu Chang, Dan Yao

et al.

Small, Journal Year: 2024, Volume and Issue: 21(1)

Published: Oct. 23, 2024

Abstract Over the past decade, precision medicine has garnered increasing attention, making significant strides in discovering new therapeutic drugs and mechanisms, resulting notable achievements symptom alleviation, pain reduction, extended survival rates. However, limited target specificity of primary inter‐individual differences have often necessitated high‐dosage strategies, leading to challenges such as restricted deep tissue penetration rates systemic side effects. Material science advancements present a promising avenue for these issues. By leveraging distinct internal features diseased regions application specific external stimuli, responsive materials can be tailored achieve targeted delivery, controllable release, biochemical reactions. This review aims highlight latest stimuli‐responsive their potential medicine. Initially, we introduce disease‐related stimuli capable elucidating reaction principles functional groups. Subsequently, provide detailed analysis representative pre‐clinical across various clinical applications, including enhancements treatment cancers, injury diseases, inflammatory infection high‐throughput microfluidic biosensors. Finally, discuss some challenges, off‐target effects, long‐term impacts nano‐materials, ethical concerns, offer insights into future perspectives materials.

Language: Английский

Citations

7
Elevated ROS Levels Caused by Reductions in GSH and AsA Contents Lead to Grain Yield Reduction in Qingke under Continuous Cropping DOI Creative Commons

Gao Xue,

Tan Jian-xin,

Kaige Yi

et al.

Plants, Journal Year: 2024, Volume and Issue: 13(7), P. 1003 - 1003

Published: March 31, 2024

Continuous spring cropping of Qingke (

Language: Английский

Citations

4
Reactive oxygen species derived from NADPH oxidase as signaling molecules regulate fatty acids and astaxanthin accumulation in Chromochloris zofingiensis DOI Creative Commons

Yi Yuan,

Tiantian Zhao, Weizheng Gao

et al.

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

Published: April 29, 2024

Abiotic stresses can increase the total fatty acid (TFA) and astaxanthin accumulation in microalgae. However, it remains unknown whether a unified signal transduction mechanism exists under different stresses. This study explored link between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) of acids Chromochloris zofingiensis three abiotic Results showed significant increases acid, astaxanthin, ROS levels nitrogen deficiency, phosphorus high-salinity stress. The introduction NADPH oxidase inhibitor diphenyleneiodonium (DPI) decreased content these components. underscores pivotal role Analysis transcriptomes across conditions following DPI addition revealed 1,445 shared differentially expressed genes (DEGs). Enrichment analysis that biotin, betalain, thiamine, glucosinolate may be important stress responses. heatmap demonstrated notably suppressed gene expression carotenoid biosynthesis pathways. Our findings underscore

Language: Английский

Citations

4
Exploration of Response Mechanisms in the Gills of Pacific Oyster (Crassostrea gigas) to Cadmium Exposure through Integrative Metabolomic and Transcriptomic Analyses DOI Creative Commons

Luyao Dong,

Yanan Sun,

Muyang Chu

et al.

Animals, Journal Year: 2024, Volume and Issue: 14(16), P. 2318 - 2318

Published: Aug. 9, 2024

Marine mollusks, including oysters, are highly tolerant to high levels of cadmium (Cd), but the molecular mechanisms underlying their response acute Cd exposure remain unclear. In this study, Pacific oyster Crassostrea gigas was used as a biological model, exposed stress for 96 h. Transcriptomic analyses gills were performed, and metabolomic further validated these results. our total 111 differentially expressed metabolites (DEMs) 2108 genes (DEGs) identified under exposure. Further revealed alterations in key metabolic pathways associated with heavy metal response. triggered physiological responses enhanced oxidative disturbances energy metabolism, changes oysters stress. Moreover, could effectively enhance tolerance detoxification ability through activating ABC transporters, enhancing glutathione metabolism sulfur relay system gill cells, regulating metabolism. This study reveals mechanism explores by using combined metabolomics transcriptome analysis.

Language: Английский

Citations

4
Acute exposure to nitrogen mustard induces rapid nuclear component regulation and delayed stress to exogenous stimuli DOI
Jin Cheng,

Wenpei Yu,

Wenzheng Zhou

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 113976 - 113976

Published: Jan. 8, 2025

Language: Английский

Citations

0