Intranasally Delivered Echinacoside Micelles Modulate Mitochondrial Fusion Against Postoperative Cognitive Dysfunction DOI

Fuwei Qi,

Yaling Liao, Chenglong Ge

et al.

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Abstract The disruption of mitochondrial homeostasis in neurons accounts for the onset and progression postoperative cognitive dysfunction (POCD). Echinacoside (ECH) can facilitate fusion to mediate neuroprotection, but its therapeutic efficacy is greatly limited by inefficient brain accumulation neuronal delivery. Herein, ECH‐encapsulated micelles are constructed from copolymer containing poly(carboxybetaine methacrylate) (PCBMA) block phenylboronic acid (PBA)‐modified poly(dimethylamino)ethyl methacrylate block, which mediates effective, brain‐targeted delivery via intranasal administration. In POCD mice, efficiently penetrate nasal mucosa betaine structure PCBMA that be recognized betaine‐GABA transporter 1 (BGT‐1) on epithelial cells, followed into hippocampus through submucosal olfactory trigeminal nerve pathways. Subsequently, internalized BGT‐1‐mediated endocytosis. over‐produced reactive oxygen species inside trigger dissociation ECH release, thereby inducing enhance neuron survival, ameliorate cerebral microenvironment, restore memory functions. This study reports a non‐invasive strategy overcome physiological barriers against drug renders profound implications treatment.

Language: Английский

Engineered mitochondrial ROS scavenger nanocomplex to enhance lung biodistribution and reduce inflammation for the treatment of ARDS DOI

Huoli Hu,

Wenjia Zhang, Yundong Zhou

et al.

Advanced Composites and Hybrid Materials, Journal Year: 2024, Volume and Issue: 7(6)

Published: Oct. 23, 2024

Language: Английский

Citations

22
Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy DOI Creative Commons
Junyan Wang,

Haowen Zhuang,

Lianqun Jia

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(11), P. 4458 - 4475

Published: Jan. 1, 2024

This study investigated the mechanism by which NR4A1 regulates mitochondrial fission factor (Mff)-related and FUN14 domain 1 (FUNDC1)-mediated mitophagy following cardiac ischemia-reperfusion injury(I/R). Our findings showed that damage regulation was positively correlated with pathological pan-apoptosis of myocardial cell mitochondria. Compared wild-type mice (WT), NR4A1-knockout exhibited resistance to injury fission, characterized activation. Results increased expression level, activating mediated Mff restoring phenotype FUNDC1. The inactivation FUNDC1 phosphorylation could not mediate normalization in a timely manner, leading an excessive stress response unfolded proteins imbalance homeostasis. process disrupted quality control network, accumulation damaged mitochondria activation pan-apoptotic programs. data indicate is novel critical target I/R exertsand negative regulatory effects Mff-mediated mito-fission inhibiting FUNDC1-mediated mitophagy. Targeting crosstalk balance between NR4A1-Mff-FUNDC1 potential approach for treating I/R.

Language: Английский

Citations

17
Mitochondrial diseases: from molecular mechanisms to therapeutic advances DOI Creative Commons
Hu Wen,

Hui Deng,

Bingyan Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 9, 2025

Abstract Mitochondria are essential for cellular function and viability, serving as central hubs of metabolism signaling. They possess various metabolic quality control mechanisms crucial maintaining normal activities. Mitochondrial genetic disorders can arise from a wide range mutations in either mitochondrial or nuclear DNA, which encode proteins other contents. These defects lead to breakdown metabolism, such the collapse oxidative phosphorylation, one mitochondria’s most critical functions. diseases, common group disorders, characterized by significant phenotypic heterogeneity. Clinical symptoms manifest systems organs throughout body, with differing degrees forms severity. The complexity relationship between mitochondria diseases results an inadequate understanding genotype-phenotype correlation these historically making diagnosis treatment challenging often leading unsatisfactory clinical outcomes. However, recent advancements research technology have significantly improved our management conditions. translations mitochondria-related therapies actively progressing. This review focuses on physiological mitochondria, pathogenesis potential diagnostic therapeutic applications. Additionally, this discusses future perspectives diseases.

Language: Английский

Citations

4
Plant Secondary Metabolites as Modulators of Mitochondrial Health: An Overview of Their Anti-Oxidant, Anti-Apoptotic, and Mitophagic Mechanisms DOI Open Access

Julia Anchimowicz,

Piotr Zielonka, Sławomir Jakieła

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 380 - 380

Published: Jan. 4, 2025

Plant secondary metabolites (PSMs) are a diverse group of bioactive compounds, including flavonoids, polyphenols, saponins, and terpenoids, which have been recognised for their critical role in modulating cellular functions. This review provides comprehensive analysis the effects PSMs on mitochondrial health, with particular emphasis therapeutic potential. Emerging evidence shows that these improve function by reducing oxidative stress, promoting biogenesis, regulating key processes such as apoptosis mitophagy. Mitochondrial dysfunction, hallmark many pathologies, neurodegenerative disorders, cardiovascular diseases, metabolic syndrome, has shown to benefit from protective PSMs. Recent studies show can dynamics, stabilise membranes, enhance bioenergetics, offering significant promise prevention treatment mitochondrial-related diseases. The molecular mechanisms underlying effects, modulation signalling pathways direct interactions proteins, discussed. integration into strategies is highlighted promising avenue improving efficacy while minimising side commonly associated synthetic drugs. also highlights need future research elucidate specific roles individual synergistic within complex plant matrices, may further optimise utility. Overall, this work valuable insights health potential natural agents targeting dysfunction.

Language: Английский

Citations

3
m6A modified pre-miR-503-5P contributes to myogenic differentiation through the activation of mTOR pathway DOI

Yalong Su,

Kaiping Deng, Zhipeng Liu

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 294, P. 139517 - 139517

Published: Jan. 5, 2025

Language: Английский

Citations

1
Single-cell atlas reveals multi-faced responses of losartan on tubular mitochondria in diabetic kidney disease DOI Creative Commons
Zhen Zhu, Guangxin Luan, Song Wu

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 21, 2025

Mitochondria are crucial to the function of renal tubular cells, and their dynamic perturbation in many aspects is an important mechanism diabetic kidney disease (DKD). Single-nucleus RNA sequencing (snRNA-seq) technology a high-throughput analysis technique for at level single cell nucleus. Here, our DKD mouse single-cell conveys more comprehensive mitochondrial profile, which helps us further understand therapeutic response this unique organelle family drugs. After high fat diet (HFD), mice were intraperitoneally injected with streptozotocin (STZ) induce DKD, then divided into three subsets: CON (healthy) subset, (vehicle) LST (losartan; 25 mg/kg/day) subset. Divide HK-2 LG (low glucose; 5 mM) HG (high 30 + 1 µ M) subsets. snRNA-seq was performed on tissues subset mice. To reveal effects losartan gene pathway changes mitochondria, Gene Ontology (GO) enrichment GSEA/GSVA scoring analyze specific proximal (PT) mitochondria treatment, including key events homeostasis such as morphology, dynamics, mitophagy, autophagic flux, respiratory chain, apoptosis, ROS generation. Preliminary validation through vitro vivo experiments, observation morphology dynamics using probes Mitotracker Red, evaluation effect electron microscopy, laser confocal immunofluorescence, Western blotting. Detection flux cells by transfecting Ad-mCherry-GFP-LC3B dual fluorescence labeled adenovirus. Various fluorescent energy detector used detect ROS, respiration mitochondrion. Through atlas kidneys, it found that treatment significantly increased percentage PT cells. differentially expressed genes showed autophagy mitochondrion pathway. Further GSEA GSVA revealed mitophagy other events, production, membrane potential, adenosine triphosphate (ATP) synthesis, involved protective thereby improving homeostasis. Consistent results also obtained cellular experiments. In addition, we highlighted subpopulation phenotype data, preliminarily validated co-localization expression Pink1 Gclc specimens patients treated losartan. Our research suggests scRNA-seq can reflect multifaceted landscape after drug these findings may provide new targets therapy level.

Language: Английский

Citations

1
MELK prevents radiofrequency ablation-induced immunogenic cell death and antitumor immune response by stabilizing FABP5 in hepatocellular malignancies DOI Creative Commons
Bufu Tang,

Wangting Xu,

Shiji Fang

et al.

Military Medical Research, Journal Year: 2025, Volume and Issue: 12(1)

Published: Jan. 27, 2025

Abstract Background Radiofrequency ablation (RFA) is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality. Understanding the biological process related RFA important improving strategy. This study aimed to identify critical targets regulating efficacy of RFA. Methods The in hepatocellular carcinoma (HCC) tumor models vivo, was analyzed by RNA sequencing technology. heat vitro HCC cells also constructed explore mechanism after cells. Nanoparticles high affinity were applied as a new therapy interfere expression maternal embryonic leucine zipper kinase (MELK). Results It found upregulated MELK expression, and inhibition promoted immunogenic cell death antitumor response, including anti-tumoral macrophage polarization increased CD8 + T cytotoxicity HCC. Mechanically, binds fatty acid-binding protein 5 (FABP5), affects its ubiquitination through K48R pathway increase stability, thereby activating B (Akt)/mammalian target rapamycin (mTOR) signaling axis weaken RFA-mediated effect. In addition, synthesis arginylglycylaspartic acid (RGD)-lipid nanoparticles (LNPs) targeting cell-intrinsic enhanced Conclusion therapeutic HCC, via RGD-LNPs provides insight into clinical combating malignant progression cancer.

Language: Английский

Citations

1
CRIP1 inhibits cutaneous melanoma progression through TFAM-mediated mitochondrial biogenesis DOI Creative Commons
Jianqiang Wu, Lixia Chen,

Pengqiang Wen

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 4, 2025

Language: Английский

Citations

1
Targeted activation on Bnip3 enhances mitophagy to prevent the progression of osteoarthritis DOI Creative Commons

Yong Gou,

Chenggui Wang,

Kejian Fu

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 51, P. 242 - 255

Published: March 1, 2025

The production of reactive oxygen species (ROS) and mitochondrial dysfunction in chondrocytes are closely related to cartilage degeneration the procedure osteoarthritis (OA). Mitophagy is responsible for scavenging ROS dysfunctional mitochondria considered a key therapeutic target treatment OA. Tiopronin, classic thiol antioxidant, has been widely studied various oxidative stress-related diseases. expression mitophagy (PINK1, PARKIN, TOMM20) intact damaged OA patients was analyzed by Western blot histological analysis. RNA sequencing (RNA-seq) analysis performed explore molecular mechanism tiopronin regulating chondrocytes, then find specific tiopronin. effects were evaluated model induced destabilisation medial meniscus (DMM), degenerative with primary from mouse human explants experiment. downstream mechanisms further investigated si-RNA knockdown mitophagy-related proteins. level negatively correlated severity We revealed that promoted anabolism extracellular matrix (ECM) hyaline alleviates vitro vivo strengthening mitophagy. Moreover, strongly activated Bnip3, protein anchored membrane, subsequently enhanced Pink1/Parkin signaling pathway. These findings indicate Bnip3-Pink1-Parkin pathway, targeted tiopronin, plays role inhibiting progression As classical drug clinic, developed new approach via this study. Based significant efficient effect degermation delay OA, it believed may become an effective candidate clinical settings.

Language: Английский

Citations

1
Phosphoglycerate mutase 5 exacerbates alcoholic cardiomyopathy in male mice by inducing prohibitin‐2 dephosphorylation and impairing mitochondrial quality control DOI Creative Commons
Jun Tao, Junxiong Qiu, Junmeng Zheng

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(8)

Published: Aug. 1, 2024

The induction of mitochondrial quality control (MQC) mechanisms is essential for the re-establishment homeostasis and cellular bioenergetics during periods stress. Although MQC activation has cardioprotective effects in various cardiovascular diseases, its precise role regulatory alcoholic cardiomyopathy (ACM) remain incompletely understood.

Language: Английский

Citations

7