Antifibrotic Agents for the Management of CKD: A Review

American Journal of Kidney Diseases, Год журнала: 2022, Номер 80(2), С. 251 - 263

Опубликована: Янв. 6, 2022

Язык: Английский

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Targeted Suppression of miRNA-33 Using pHLIP Improves Atherosclerosis Regression

Circulation Research, Год журнала: 2022, Номер 131(1), С. 77 - 90

Опубликована: Май 10, 2022

miRNA therapeutics have gained attention during the past decade. These oligonucleotide treatments can modulate expression of miRNAs in vivo and could be used to correct imbalance gene found human diseases such as obesity, metabolic syndrome, atherosclerosis. The efficacy current anti-miRNA technologies hindered by physiological cellular barriers delivery into targeted cells nature that allows one target an entire pathway may lead deleterious off-target effects. For these reasons, novel systems inhibit specific tissues will important for developing effective therapeutic strategies numerous including

Язык: Английский

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microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis

JCI Insight, Год журнала: 2023, Номер 8(4)

Опубликована: Янв. 10, 2023

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. Recent findings have shown marked metabolic reprogramming associated with changes in mitochondrial homeostasis autophagy during fibrosis. The microRNA-33 (miR-33) family of microRNAs (miRNAs) encoded within the introns sterol regulatory element binding protein (SREBP) genes are master regulators fatty acid (FA) metabolism. miR-33 controls macrophage immunometabolic response enhances biogenesis, FA oxidation, cholesterol efflux. Here, we show that levels increased bronchoalveolar lavage (BAL) cells isolated from patients IPF compared healthy controls. We demonstrate specific genetic ablation macrophages protects against bleomycin-induced absence improves increases while decreasing inflammatory after bleomycin injury. Notably, pharmacological inhibition via administration anti-miR-33 peptide nucleic acids (PNA-33) attenuates different vivo ex mice human models These studies elucidate major role regulation uncover potentially novel therapeutic approach to treat this

Язык: Английский

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microRNA-33 controls hunger signaling in hypothalamic AgRP neurons

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 8, 2024

Abstract AgRP neurons drive hunger, and excessive nutrient intake is the primary driver of obesity associated metabolic disorders. While many factors impacting central regulation feeding behavior have been established, role microRNAs in this process poorly understood. Utilizing unique mouse models, we demonstrate that miR-33 plays a critical neurons, loss leads to increased feeding, obesity, dysfunction mice. These effects include multiple target genes involved mitochondrial biogenesis fatty acid metabolism. Our findings elucidate key regulatory pathway regulated by non-coding RNA impacts hunger controlling bioenergetic processes with activation providing alternative therapeutic approaches modulate diseases.

Язык: Английский

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Unlocking the potential of chemically modified peptide nucleic acids for RNA-based therapeutics

RNA, Год журнала: 2023, Номер 29(4), С. 434 - 445

Опубликована: Янв. 18, 2023

RNA therapeutics have emerged as next-generation therapy for the treatment of many diseases. Unlike small molecules, targeted drugs are not limited by availability binding pockets on protein, but rather utilize Watson-Crick (WC) base-pairing rules to recognize target and modulate gene expression. Antisense oligonucleotides (ASOs) present a powerful therapeutic approach treat disorders triggered genetic alterations. ASOs cognate site alter Nine single-stranded been approved clinical use several candidates in late-stage trials both rare common Several chemical modifications, including phosphorothioates, locked nucleic acid, phosphorodiamidate, morpholino, peptide acids (PNAs), investigated efficient targeting. PNAs synthetic DNA mimics where deoxyribose phosphate backbone is replaced N-(2-aminoethyl)-glycine units. The neutral pseudopeptide contributes enhanced affinity high biological stability. hybridize with complementary act steric hindrance--based mechanism. In last three decades, various PNA designs, delivery strategies explored demonstrate their potential an effective safe RNA-targeting platform. This review covers advances PNA-mediated targeting coding noncoding RNAs myriad applications.

Язык: Английский

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Baicalin ameliorates renal fibrosis by upregulating CPT1α-mediated fatty acid oxidation in diabetic kidney disease

Phytomedicine, Год журнала: 2023, Номер 122, С. 155162 - 155162

Опубликована: Окт. 22, 2023

Язык: Английский

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Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney

Redox Biology, Год журнала: 2023, Номер 68, С. 102957 - 102957

Опубликована: Ноя. 3, 2023

Progressive respiratory failure is the primary cause of death in coronavirus disease 2019 (COVID-19) pandemic. It final outcome acute distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response, metabolic derangement and ultimate tissue scarring. A positive balance cellular energy may result crucial for recovery clinical COVID-19. Hence, we asked if two key pathways involved generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling fatty acid oxidation (FAO) could be beneficial. We tested drugs metformin (AMPK activator) baicalin (CPT1A different experimental models mimicking COVID-19 associated inflammation lung kidney. also studied cohorts patients that had been previously treated with metformin. These ameliorated damage ARDS animal model, while activation AMPK/ACC increased mitochondrial function decreased TGF-β-induced fibrosis, apoptosis markers epithelial cells. Similar results were observed indole derivatives, IND6 IND8 AMPK activating capacity. Consistently, a reduced time hospitalization need intensive care was exposed to Baicalin mitigated pro-inflammatory bone marrow-derived macrophages (BMDMs) kidney fibrosis injury, another target In human cells, both improved prevented renal cell dedifferentiation. Our support favoring production through enhanced FAO prove useful prevention COVID-19-induced damage.

Язык: Английский

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Metabolic reprogramming heterogeneity in chronic kidney disease

FEBS Open Bio, Год журнала: 2023, Номер 13(7), С. 1154 - 1163

Опубликована: Фев. 1, 2023

Fibrosis driven by excessive accumulation of extracellular matrix (ECM) is the hallmark chronic kidney disease (CKD). Myofibroblasts, which are cells responsible for ECM production, activated cross talk with injured proximal tubule and immune cells. Emerging evidence suggests that alterations in metabolism not only a feature but also play an influential role pathogenesis renal fibrosis. The application omics technologies to cell-tracing animal models follow-up functional data suggest cell-type-specific metabolic shifts have particular roles fibrogenic response. In this review, we cover main reprogramming outcomes fibrosis provide future perspective on field fibrometabolism.

Язык: Английский

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Mechanism of LncRNA-MiRNA in Renal Intrinsic Cells of Diabetic Kidney Disease and Potential Therapeutic Direction

DNA and Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

The occurrence of diabetic kidney disease (DKD), a critical microvascular issue in diabetes, is progressively on the rise. In recent years, long noncoding RNAs (lncRNAs) have garnered considerable attention as novel and layer biological regulation. Our knowledge regarding roles underlying mechanisms lncRNAs various diseases, including DKD, continues to evolve. Similarly, microRNAs (miRNAs), which are small RNAs, been recognized crucial contributors cellular processes pathogenesis. Emerging studies highlighted complex interactions between miRNAs, particularly context underscoring their importance human diseases. Renal intrinsic cell damage an important cause inducing DKD. Persistent high glucose stimulation leads remodeling renal cells cascade pathological changes. This article aims review literature lncRNAs-mediated regulation miRNAs affecting DKD propose molecular-level therapeutic strategies for Through in-depth investigation this dynamic molecular interaction, we can gain profound understanding potential nephropathy, potentially identifying new targets intervention paving way personalized effective treatments.

Язык: Английский

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Targeting Acidic Diseased Tissues by pH-Triggered Membrane-Associated Peptide Folding

Frontiers in Bioengineering and Biotechnology, Год журнала: 2020, Номер 8

Опубликована: Апрель 28, 2020

The advantages of targeted therapy have motivated many efforts to find distinguishing features between the molecular cell surface landscapes diseased and normal cells. Typically, been proteins, lipids or carbohydrates, but other approaches are emerging. In this discussion, we examine use acidity as a feature that can be exploited by using pH-sensitive peptide folding target agents surfaces cytoplasms.

Язык: Английский

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