Pharmacologic Approaches to Improve Mitochondrial Function in AKI and CKD

Journal of the American Society of Nephrology, Journal Year: 2017, Volume and Issue: 28(10), P. 2856 - 2865

Published: Aug. 4, 2017

AKI is associated with high morbidity and mortality, it predisposes to the development progression of CKD. Novel strategies that minimize halt CKD are urgently needed. Normal kidney function involves numerous different cell types, such as tubular epithelial cells, endothelial podocytes, working in concert. This delicate balance many energy-intensive processes. Fatty acids preferred energy substrates for kidney, defects fatty acid oxidation mitochondrial dysfunction universally involved diverse causes review provides an overview ATP production demands summarizes preclinical clinical evidence New therapeutic targeting mitochondria protection cellular bioenergetics presented, emphasis on those have been evaluated animal models Targeting upstream damage may offer advantages compared downstream inflammatory fibrosis

Language: Английский

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Mitochondrial dysfunction in diabetic kidney disease

Clinica Chimica Acta, Journal Year: 2019, Volume and Issue: 496, P. 108 - 116

Published: July 2, 2019

Language: Английский

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ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule

Science Advances, Journal Year: 2020, Volume and Issue: 6(41)

Published: Oct. 9, 2020

An SS31 prodrug improved AKI therapy via rapid distribution in the kidney and long-term retention renal tubule.

Language: Английский

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Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus

Bioactive Materials, Journal Year: 2023, Volume and Issue: 27, P. 409 - 428

Published: April 21, 2023

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, tissue necrosis. To solve these issues, we developed double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) hyaluronic acid methacrylate (HAMA), enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, mitochondria-targeted peptide, maintains reduces reactive oxygen species (ROS) thus regulates macrophage polarization, as well promoting cell proliferation migration, while MPDA NPs not only scavenge ROS exert an anti-bacterial effect photothermal treatment under near-infrared light irradiation, but also control release of SS31 response ROS. This F127DA/HAMA-MPDA@SS31 (FH-M@S) hydrogel characteristics adhesion, superior biocompatibility mechanical properties which can adapt irregular wounds at different body sites provide sustained MPDA@SS31 (M@S) NPs. In addition, diabetic rat full thickness skin defect model, the FH-M@S promoted M2 collagen deposition, neovascularization healing. Therefore, exhibits promising therapeutic potential for regeneration.

Language: Английский

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The multi-tissue landscape of somatic mtDNA mutations indicates tissue-specific accumulation and removal in aging

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 17, 2023

Accumulation of somatic mutations in the mitochondrial genome (mtDNA) has long been proposed as a possible mechanism and tissue dysfunction that occurs during aging. A thorough characterization age-associated mtDNA hampered by limited ability to detect low-frequency mutations. Here, we used Duplex Sequencing on eight tissues an aged mouse cohort >89,000 independent show significant tissue-specific increases aging across all examined which did not correlate with content function. G→A/C→T substitutions, indicative replication errors and/or cytidine deamination, were predominant mutation type increased age, whereas G→T/C→A oxidative damage, second most common type, but increase age regardless tissue. We also clonal expansions is tissue- type-dependent. Unexpectedly, associated damage rarely formed clones any significantly reduced hearts kidneys mice treated at late elamipretide or nicotinamide mononucleotide. Thus, lack accumulation damage-linked suggests life-long dynamic clearance either lesions genomes harboring damage.

Language: Английский

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Photodynamic Therapy Induced Mitochondrial Targeting Strategies for Cancer Treatment: Emerging Trends and Insights

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(4), P. 1591 - 1608

Published: Feb. 23, 2024

The perpetuity of cancer prevalence at a global level calls for development novel therapeutic approaches with improved targetability and reduced adverse effects. Conventional treatments have multitude limitations such as nonselectivity, invasive nature, severe Chemotherapy is also losing its efficacy because the multidrug resistance in majority cancers. To address these issues, selective targeting-based are being explored an effective treatment. Mitochondria, moderator crucial cellular pathways like metabolism, apoptosis, reactive oxygen species (ROS) homeostasis, targeting site. Mitochondria-targeted photodynamic therapy (PDT) has arisen potential approach this endeavor. By designing photosensitizers (PSs) that preferentially accumulate mitochondria, PDT offers localized technique to induce cytotoxicity cells. In review, we intend explore principles challenges associated mitochondria-targeted PDT, including variability mitochondrial function, mitochondria-specific PSs, targeted nanocarrier-based monotherapy, combination therapies. hurdles faced by emerging strategy respect safety, optimization, clinical translation, scalability discussed. Nonetheless, exhibits significant capacity treatment, especially other modalities. With perpetual research technological advancements, treatment great addition arsenal options, providing better tumor while reducing damage surrounding healthy tissues. This review emphasizes current status limitations, future prospects pursuit safe efficacious therapy.

Language: Английский

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Cellular senescence in the aging and diseased kidney

Journal of Cell Communication and Signaling, Journal Year: 2017, Volume and Issue: 12(1), P. 69 - 82

Published: Dec. 19, 2017

The program of cellular senescence is involved in both the G1 and G2 phase cell cycle, limiting G1/S G2/M progression respectively, resulting prolonged cycle arrest. Cellular normal wound healing. However, multiple organs display increased senescent numbers during natural aging after injury, suggesting that cells can have beneficial as well detrimental effects organismal disease. Also kidney, accumulate various compartments with advancing age renal In experimental studies, forced apoptosis induction through clearance leads to better preservation kidney function aging. Recent groundbreaking studies demonstrate depletion INK-ATTAC transgene-mediated or cell-penetrating FOXO4-DRI peptide induced apoptosis, reduced age-associated damage dysfunction organs, particular performance lifespan. Senescence also oncology therapeutic by senolytic drugs has been studied human cancers. Although models injury are lacking, their dose side on other suggest targeted delivery might be needed for successful application treatment this review, we discuss (i) current understanding mechanisms associated pathways senescence, (ii) evidence occurrence causality organ (iii) strategies (senotherapy) including targeting, all context

Language: Английский

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Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy

Cancers, Journal Year: 2019, Volume and Issue: 12(1), P. 4 - 4

Published: Dec. 18, 2019

The mitochondrion is a dynamic eukaryotic organelle that controls lethal and vital functions of the cell. Being critical center metabolic activities involved in many diseases, mitochondria have been attracting attention as potential target for therapeutics, especially cancer treatment. Structural functional differences between healthy cancerous mitochondria, such membrane potential, respiratory rate, energy production pathway, gene mutations, could be employed design selective targeting systems mitochondria. A number mitochondria-targeting compounds, including mitochondria-directed conventional drugs, mitochondrial proteins/metabolism-inhibiting agents, mitochondria-targeted photosensitizers, discussed. Recently, certain drug-free approaches introduced an alternative to induce dysfunction, intramitochondrial aggregation, self-assembly, biomineralization. In this review, we discuss recent progress therapy from approach drug/cytotoxic agent conjugates advanced approaches.

Language: Английский

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Enhanced efficiency of mitochondria-targeted peptide SS-31 for acute kidney injury by pH-responsive and AKI-kidney targeted nanopolyplexes

Biomaterials, Journal Year: 2019, Volume and Issue: 211, P. 57 - 67

Published: May 7, 2019

Language: Английский

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Mitochondria-Targeted Antioxidants: A Step towards Disease Treatment

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 18

Published: Dec. 5, 2020

Mitochondria are the main organelles that produce adenosine 5 ′ -triphosphate (ATP) and reactive oxygen species (ROS) in eukaryotic cells meanwhile susceptible to oxidative damage. The irreversible damage mitochondria has been implicated various human diseases. Increasing evidence indicates therapeutic potential of mitochondria-targeted antioxidants (MTAs) for damage-associated In this article, we introduce advantageous properties MTAs compared with conventional (nontargeted) ones, review different delivery systems antioxidants, summarize their experimental results disease treatments animal models clinical trials. combined demonstrates mitochondrial redox homeostasis is a target treatment. Meanwhile, limitations prospects exploiting discussed, which might pave ways further trial design drug development.

Language: Английский

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