Poly(A) Tail Length of Messenger RNA Regulates Translational Efficiency of the Mitochondria-Targeting Delivery System DOI
Naoto Yoshinaga, Keiji Numata

ACS Biomaterials Science & Engineering, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Mitochondria are essential for cellular functions, such as energy production. Human mitochondrial DNA (mtDNA), encoding 13 distinct genes, two rRNA, and 22 tRNA, is crucial maintaining vital along with nuclear-encoded proteins. However, mtDNA prone to somatic mutations due replication errors reactive oxygen species exposure. These can accumulate, leading heteroplasmic conditions associated severe metabolic diseases. Therefore, developing methodologies improve health highly demanded. Introducing nucleic acids directly into mitochondria a promising strategy control gene expression. Messenger RNA (mRNA) delivery especially offers several advantages faster expression reduced risk of genome integration if accidentally delivered the cell nucleus. In this study, we investigated effect poly(A) tail length mRNA on translation achieve efficient We used peptide-based targeting system, mitoNEET-(RH)

Language: Английский

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

23
Association between blood metals mixture and chronic kidney disease in adults: NHANES 2013-2016 DOI

Yican Wang,

Hua Zhang, Peng Tang

et al.

Journal of Trace Elements in Medicine and Biology, Journal Year: 2024, Volume and Issue: 83, P. 127395 - 127395

Published: Jan. 15, 2024

Language: Английский

Citations

8
Mitochondrial dysfunction in the pathophysiology of renal diseases DOI
Yuxian Guo, Ruochen Che, Peipei Wang

et al.

AJP Renal Physiology, Journal Year: 2024, Volume and Issue: 326(5), P. F768 - F779

Published: March 7, 2024

Mitochondria are essential organelles in the human body, serving as metabolic factory of whole organism. When mitochondria dysfunctional, it can affect all organs body. The kidney is rich mitochondria, and its function closely related to development diseases. Studying relationship between disease progression great interest. In past decade, scientists have made inspiring progress investigating role pathophysiology renal This article discusses various mechanisms for maintaining mitochondrial quality, including energetics, biogenesis, dynamics, DNA repair, proteolysis unfolded protein response, autophagy, mitochondria-derived vesicles, mitocytosis. also highlights cross talk other organelles, with a focus on Finally, concludes an overview mitochondria-related clinical research.

Language: Английский

Citations

7
Exploring the Role of Mitochondrial Hydrogen Sulfide in Maintaining Polarity and mtDNA Integrity with a Multichannel Fluorescent Probe DOI
Shuai Mu,

Taihe Han,

Xiaoyun Zhang

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(50), P. 18460 - 18469

Published: Nov. 22, 2023

Abnormal mitochondrial state has been implicated in the pathogenesis of various diseases including neurodegenerative disorders, myopathies, cardiovascular diseases, and cancers. Assessing functionality can be achieved by monitoring alterations polarity DNA (mtDNA) integrity, which serve as valuable biomarkers. Hydrogen sulfide (H2S), a gaseous signaling molecule, plays regulatory role respiratory chain activity, ATP synthesis, calcium ion balance, thereby influencing cellular metabolism signal transduction. Investigating interplay between H2S, polarity, mtDNA enhance our understanding underlying mechanisms involved H2S-mediated functions. To address this, we designed mitochondria-targeted multichannel fluorescent probe, HNA, capable cascaded detection H2S well parallel mtDNA. The probe exhibited significant turn-on response to emitting at approximately 604 nm, while product HNAP demonstrated high sensitivity within wavelength range 526–591 nm. Additionally, was able bind DNA, resulting an enhanced long-wave emission 668 Facilitated study provides novel insights into maintaining validates its protective effect on through antioxidative mechanisms. Overall, this work proposes potential therapeutic strategy for modulating inflammatory process mitochondrial-related diseases.

Language: Английский

Citations

14
Association of mitochondrial DNA copy number with chronic kidney disease in older adults DOI Creative Commons
Liu Yang, Ying Pan, Zijian Tian

et al.

BMC Geriatrics, Journal Year: 2023, Volume and Issue: 23(1)

Published: Aug. 24, 2023

Mitochondrial dysfunction in kidney cells has been implicated the pathogenesis of chronic disease (CKD). Estimation mitochondrial DNA copy number (mtDNA-CN) is considered a convenient method for representing function large samples. However, no study investigated association between mtDNA-CN and CKD older adults with highest prevalence. The objective to examine cross-sectional prospective associations values risk determine whether represents novel potential biomarker recognition risk.In Chinese community-based cohort over 65-year-olds, we included 14,467 participants (52.6% females). was defined by eGFR < 60 mL/min/1.73 m2 or ICD-10 codes (patients = 3831 (26.5%)). Participants had peripheral blood levels calculated from probe intensities Axiom CAS Array.The prevalence decreased per 1-SD increment, independent established factors (odds ratio [OR] SD 0.90, 95% confidence interval [CI] 0.86, 0.93, P 0.001), comparable strength these factors. Furthermore, progression stratified according worsening categories. more severe stage gradually as increased (P trend 0.001). Non-CKD quartile lower developing compared lowest within 2 years follow-up, reducing 36% (95% CI 0.42, 0.97; 0.037).Based on analysis largest sample date investigating adults, higher were found be associated CKD, suggesting that reduced level factor CKD.

Language: Английский

Citations

10
Wasp venom-induced acute kidney injury: current progress and prospects DOI Creative Commons

Fanglin Yu,

Ling Wang, Hai Yuan

et al.

Renal Failure, Journal Year: 2023, Volume and Issue: 45(2)

Published: Sept. 19, 2023

Wasp venom can trigger local and systemic reactions, with the kidneys being commonly affected, potentially causing acute kidney injury (AKI). Despite of recent advances, our knowledge on underlying mechanisms toxicity targeted therapies remain poor. AKI result from direct nephrotoxic effects wasp or secondary rhabdomyolysis intravascular hemolysis, which will release myoglobin free hemoglobin. Inflammatory responses play a central role in these pathological mechanisms. Noteworthily, successful establishment suitable experimental model assist basic research clinical advancements related to venom-induced AKI. The combination therapeutic plasma exchange continuous renal replacement therapy appears be preferred treatment for In addition, studies cilastatin varespladib have shown their potential as agents. This review summarizes available evidence AKI, particular focus inflammatory targets drugs, and, therefore, aiming support development against

Language: Английский

Citations

10
Current role of biomarkers in the initiation and weaning of kidney replacement therapy in acute kidney injury DOI
Kanwalpreet Sodhi, Gunjan Chanchalani, Niraj Tyagi

et al.

World Journal of Nephrology, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 18, 2025

The occurrence of acute kidney injury (AKI) in critically ill patients is often associated with increased morbidity and mortality rates. Despite extensive research, a consensus yet to be arrived, especially regarding the optimal timing indications for initiation replacement therapy (KRT) patients. There no clear guidance available on weaning from KRT. More recently, various biomarkers have produced promising prognostic prediction such patients, need KRT its termination. Most these are indicative damage stress, rather than recovery. However, large-scale validation studies required guide cutoff values among different patient cohorts so as identify optimum This article reviews detail summarizes individual roles decision-making process termination AKI supportive literature.

Language: Английский

Citations

0
Piplartine alleviates sepsis-induced acute kidney injury by inhibiting TSPO-mediated macrophage pyroptosis DOI Creative Commons
Rui Gong,

Gangyu Long,

Qian Wang

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167687 - 167687

Published: Jan. 1, 2025

Language: Английский

Citations

0
Discovery of a DNA repair-associated radiosensitivity index for predicting radiotherapy efficacy in breast cancer DOI Creative Commons
Jianguang Lin, Hainan Yang,

Rongfu Huang

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 25, 2025

Purpose Radiotherapy is a cornerstone of breast cancer (BRCA) treatment. Accurately predicting tumor radiosensitivity critical for optimizing therapeutic outcomes and personalizing treatment strategies. DNA repair pathways are key determinants radiotherapy response. Thus, we aimed to develop novel repair-related model identify potential targets enhancing efficacy. Methods A retrospective study was conducted using data from 942 BRCA patients TCGA database. model, comprising index, developed LASSO regression analysis. Patients were stratified into radiosensitive (RS) radioresistant (RR) groups based on their index (RSI). Associations between the RSI, clinicopathological parameters, PD-L1 status analyzed. The CIBERSORT ESTIMATE algorithms employed characterize immune landscape microenvironment. Tumor Immune Dysfunction Exclusion (TIDE) algorithm pRRophetic platform used predict responses. Key genes identified in further validated vitro qRT-PCR experiments. Results We successfully constructed incorporating 10 genes. RS group exhibited significantly better prognosis compared RR group, but this benefit limited those receiving radiotherapy. This survival associated with signature absent who did not receive displayed distinct molecular profile characterized by enrichment TGF-β signaling protein secretion pathways, potentially contributing enhanced radiosensitivity. Furthermore, increased infiltration cells. Notably, RS-PD-L1-high subgroup demonstrated most favorable highest cell infiltration, highlighting responsiveness immunotherapy. In addition, heightened sensitivity CDK HER2 inhibitors. Conversely, resistance DNA-damaging drugs. These findings supported experiments MCF-7 MCF-7/IR lines, confirming differential expression Conclusion conclusion, established cancer. Our reveals strong association radiosensitivity, antitumor immunity, immunotherapy benefit, particularly within subgroup.

Language: Английский

Citations

0
Vacuole and mitochondria patch protein Mcp1 of Saccharomyces boulardii impairs the oxidative stress response of Candida albicans by regulating 2-phenylethanol DOI Creative Commons

Yunyun Wei,

Xiaohui Zhao, Chuanqi Li

et al.

Microbial Cell Factories, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 22, 2025

Vacuole and mitochondria patch (vCLAMP) protein Mcp1 is crucial in eukaryotic cells response to environmental stress, but the mechanism of Saccharomyces boulardii (S. boulardii) against pathogenic fungi unclear. This work first explored role S. Candida albicans (C. albicans). The results showed that located on vacuolar mitochondrial membrane boulardii. Overexpression inhibited adhesion hyphal formation C. vitro. mice model intestinal infection revealed WT-pGK1-MCP1 mutant enhanced ability antagonize infecting gut. High performance liquid chromatography-mass spectrometry analysis demonstrated overexpressing promoted production 2-phenylethanol. latter a secondary metabolite boulardii, can inhibit biofilm albicans. reverse transcription polymerase chain reaction western blotting confirmed 2-phenylethanol by regulating expression level Aro10. Notably, RNA-sequencing Gene Ontology enrichment analyses impaired oxidative stress reveals critical metabolism, which provide theoretical basis for as antifungal biologic therapy prevent treat infection.

Language: Английский

Citations

0