Mitochondrial dysfunction: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 15, 2024

Abstract Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation disease progression. Particularly, mitochondrial dysfunctions identified many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, cancer. However, the multifaceted nature elusive phenotypic threshold dysfunction complicate our understanding contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among most important therapeutic targets. In recent years, strategies targeting have continuously emerged transitioned clinical trials. Advanced intervention such as using healthy replenish or replace damaged mitochondria, has shown promise preclinical trials various Mitochondrial components, mtDNA, mitochondria-located microRNA, associated proteins can be potential agents augment function immunometabolic diseases tissue injuries. Here, we review current knowledge pathophysiology concrete examples We also summarize treat perspective dietary supplements targeted therapies, well translational situation related pharmacology agents. Finally, this discusses innovations applications transplantation an advanced promising treatment.

Language: Английский

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MitoEVs: A new player in multiple disease pathology and treatment

Journal of Extracellular Vesicles, Journal Year: 2023, Volume and Issue: 12(4)

Published: March 31, 2023

Mitochondrial damage plays vital roles in the pathology of many diseases, such as cancers, neurodegenerative aging, metabolic diseases and types organ injury. However, regulatory mechanism mitochondrial functions among different cells or organs vivo is still unclear, efficient therapies for attenuating are urgently needed. Extracellular vesicles (EVs) cell-derived nanovesicles that can deliver bioactive cargoes organs. Interestingly, recent evidence shows diverse contents enriched certain EV subpopulations, mitoEVs components to affect recipient under conditions, which has emerged a hot topic this field. overview essential questions with respect event remain elusive. In review, we provide global view biology mainly focus on detailed sorting mechanisms, functional contents, biological effects mitoEVs. We also discuss pathogenic therapeutic highlight their potential disease biomarkers clinical translation. This review will insights into drug development various injury-related diseases.

Language: Английский

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Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: March 6, 2023

Plant-derived nanovesicles (PDNVs) have been proposed as a major mechanism for the inter-kingdom interaction and communication, but effector components enclosed in vesicles mechanisms involved are largely unknown. The plant Artemisia annua is known an anti-malaria agent that also exhibits wide range of biological activities including immunoregulatory anti-tumor properties with to be further addressed. Here, we isolated purified exosome-like particles from A. annua, which were characterized by nano-scaled membrane-bound shape hence termed artemisia-derived (ADNVs). Remarkably, demonstrated inhibit tumor growth boost immunity mouse model lung cancer, primarily through remolding microenvironment reprogramming tumor-associated macrophages (TAMs). We identified plant-derived mitochondrial DNA (mtDNA), upon internalized into TAMs via vesicles, molecule induce cGAS-STING pathway driving shift pro-tumor phenotype. Furthermore, our data showed administration ADNVs greatly improved efficacy PD-L1 inhibitor, prototypic immune checkpoint tumor-bearing mice. Together, present study, first time, knowledge, unravels wherein medical mtDNA, nanovesicles, induces immunostimulatory signaling mammalian cells resetting promoting eradication.

Language: Английский

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Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: June 12, 2023

Non-small cell lung cancer (NSCLC) is a worldwide health threat with high annual morbidity and mortality. Chemotherapeutic drugs such as paclitaxel (PTX) have been widely applied clinically. However, systemic toxicity due to the non-specific circulation of PTX often leads multi-organ damage, including liver kidney. Thus, it necessary develop novel strategy enhance targeted antitumor effects PTX.Here, we engineered exosomes derived from T cells expressing chimeric antigen receptor (CAR-Exos), which mesothelin (MSLN)-expressing Lewis (MSLN-LLC) through anti-MSLN single-chain variable fragment (scFv) CAR-Exos. was encapsulated into CAR-Exos (PTX@CAR-Exos) administered via inhalation an orthotopic mouse model.Inhaled PTX@CAR-Exos accumulated within tumor area, reduced size, prolonged survival little toxicity. In addition, reprogrammed microenvironment reversed immunosuppression, attributed infiltrating CD8+ elevated IFN-γ TNF-α levels.Our study provides nanovesicle-based delivery platform promote efficacy chemotherapeutic fewer side effects. This may ameliorate present obstacles clinical treatment cancer.

Language: Английский

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Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 25, 2024

Abstract Sepsis, a prevalent critical condition in clinics, continues to be the leading cause of death from infections and global healthcare issue. Among organs susceptible harmful effects sepsis, lungs are notably most frequently affected. Consequently, patients with sepsis predisposed developing acute lung injury (ALI), severe cases, respiratory distress syndrome (ARDS). Nevertheless, precise mechanisms associated onset ALI/ARDS remain elusive. In recent years, there has been growing emphasis on role endothelial cells (ECs), cell type integral barrier function, their interactions various stromal sepsis-induced ALI/ARDS. this comprehensive review, we summarize involvement intricate interplay immune cells, including pulmonary epithelial fibroblasts, pathogenesis ALI/ARDS, particular placed discussing several pivotal pathways implicated process. Furthermore, discuss potential therapeutic interventions for modulating functions relevant present strategy managing

Language: Английский

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Mitochondria as secretory organelles and therapeutic cargos

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(1), P. 66 - 85

Published: Jan. 4, 2024

Abstract Mitochondria have been primarily considered intracellular organelles that are responsible for generating energy cell survival. However, accumulating evidence suggests mitochondria secreted into the extracellular space under physiological and pathological conditions, these play diverse roles by regulating metabolism, immune response, or differentiation/maturation in target cells. Furthermore, increasing amount of research shows therapeutic effects local systemic administration various disease models. These findings led to growing interest exploring as potential agents. Here, we discuss emerging extracellularly shed light on their functions beyond production. Additionally, provide information outcomes mitochondrial transplantation animal models diseases an update ongoing clinical trials, underscoring using a novel intervention.

Language: Английский

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Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics

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

Published: June 6, 2024

Abstract Adipose-derived stem cells (ADSCs) are a subset of mesenchymal (MSCs) isolated from adipose tissue. They possess remarkable properties, including multipotency, self-renewal, and easy clinical availability. ADSCs also capable promoting tissue regeneration through the secretion various cytokines, factors, extracellular vesicles (EVs). ADSC-derived EVs (ADSC-EVs) act as intercellular signaling mediators that encapsulate range biomolecules. These have been found to mediate therapeutic activities donor by proliferation migration effector cells, facilitating angiogenesis, modulating immunity, performing other specific functions in different tissues. Compared themselves, ADSC-EVs offer advantages such fewer safety concerns more convenient transportation storage for application. As result, these received significant attention cell-free agents with potential future application regenerative medicine. In this review, we focus on recent research progress regarding medical use across conditions, wound healing, chronic limb ischemia, myocardial infarction, diabetic nephropathy, fat graft survival, bone regeneration, cartilage tendinopathy tendon peripheral nerve acute lung injury, among others. We discuss underlying mechanisms responsible inducing effects. believe deciphering biological effects, associated will provide foundation developing novel approach Graphical

Language: Английский

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Biointerface‐Engineered Hybrid Nanovesicles for Targeted Reprogramming of Tumor Microenvironment

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(41)

Published: June 9, 2024

Abstract The tumor microenvironment (TME) of typical types such as triple‐negative breast cancer is featured by hypoxia and immunosuppression with abundant tumor‐associated macrophages (TAMs), which also emerge potential therapeutic targets for antitumor therapy. M1‐like macrophage‐derived exosomes (M1‐Exos) have emerged a promising candidate their tumor‐targeting macrophage‐polarization capabilities. However, the limited drug‐loading efficiency stability M1‐Exos hindered effectiveness in applications. Here, hybrid nanovesicle developed integrating AS1411 aptamer‐conjugated liposomes (AApt‐Lips), termed M1E/AALs. obtained M1E/AALs are loaded perfluorotributylamine (PFTBA) IR780, P‐I, to construct P‐I@M1E/AALs reprogramming TME alleviating engineering TAMs. P‐I@M1E/AAL‐mediated therapy enhances situ generation reactive oxygen species, repolarizes TAMs toward an phenotype, promotes infiltration T lymphocytes. synergistic based on significantly suppresses growth prolongs survival 4T1‐tumor‐bearing mice. By multiple treatment modalities, P‐I@M1E/AAL nanoplatform demonstrates approach overcoming hypoxic immunosuppressive targeted TAM enhanced photodynamic immunotherapy. This study highlights innovative TAM‐engineering platform tumors characterized TME.

Language: Английский

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

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

Published: Oct. 23, 2024

Language: Английский

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Serine synthesis sustains macrophage IL-1β production via NAD+-dependent protein acetylation

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(4), P. 744 - 759.e6

Published: Jan. 23, 2024

Language: Английский

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