Peroxisome Proliferator-Activated Receptors and the Hallmarks of Cancer

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2432 - 2432

Published: Aug. 5, 2022

Peroxisome proliferator-activated receptors (PPARs) function as nuclear transcription factors upon the binding of physiological or pharmacological ligands and heterodimerization with retinoic X receptors. Physiological include fatty acids fatty-acid-derived compounds low specificity for different PPAR subtypes (alpha, beta/delta, gamma). For each subtypes, specific agonists antagonists, well pan-agonists, are available. In agreement their natural ligands, PPARs mainly focused on targets treatment metabolic syndrome its associated complications. Nevertheless, many publications available that implicate in malignancies. several instances, they controversial very similar models. Thus, to better predict potential use modulators personalized medicine therapies against malignancies, it seems necessary timely review three relation didactic concept cancer hallmark capabilities. We previously described functions beta/delta respect hallmarks reviewed implications all angiogenesis. current updates our knowledge beta extends alpha gamma.

Language: Английский

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Podocyte injury of diabetic nephropathy: Novel mechanism discovery and therapeutic prospects

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115670 - 115670

Published: Oct. 13, 2023

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, posing significant challenges in terms early prevention, clinical diagnosis, and treatment. Consequently, it has emerged as major contributor to end-stage renal disease. The glomerular filtration barrier, composed podocytes, endothelial cells, the basement membrane, plays vital role maintaining function. Disruptions podocyte function, including hypertrophy, shedding, reduced density, apoptosis, can impair integrity resulting elevated proteinuria, abnormal rate, increased creatinine levels. Hence, recent research increasingly focused on injury DN, with growing emphasis exploring therapeutic interventions targeting injury. Studies have revealed that factors such lipotoxicity, hemodynamic abnormalities, oxidative stress, mitochondrial dysfunction, impaired autophagy contribute This review aims summarize underlying mechanisms DN provide an overview current status regarding experimental drugs DN. findings presented herein may offer potential targets strategies for management associated

Language: Английский

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USP28 Serves as a Key Suppressor of Mitochondrial Morphofunctional Defects and Cardiac Dysfunction in the Diabetic Heart

Circulation, Journal Year: 2023, Volume and Issue: 149(9), P. 684 - 706

Published: Nov. 23, 2023

BACKGROUND: The majority of people with diabetes are susceptible to cardiac dysfunction and heart failure, conventional drug therapy cannot correct diabetic cardiomyopathy progression. Herein, we assessed the potential role therapeutic value USP28 (ubiquitin-specific protease 28) on metabolic vulnerability cardiomyopathy. METHODS: type 2 mouse model was established using db/db leptin receptor–deficient mice high-fat diet/streptozotocin–induced mice. Cardiac-specific knockout in background generated by crossbreeding db/m Myh6-Cre + /USP28 fl/fl Recombinant adeno-associated virus serotype 9 carrying under troponin T promoter injected into High glucose plus palmitic acid–incubated neonatal rat ventricular myocytes human induced pluripotent stem cell-derived cardiomyocytes were used imitate vitro. molecular mechanism explored through RNA sequencing, immunoprecipitation mass spectrometry analysis, protein pull-down, chromatin assay. RESULTS: Microarray profiling UPS (ubiquitin-proteasome system) basis hearts patients’ demonstrated that ventricle presented a significant reduction expression. Diabetic exhibited more severe progressive dysfunction, lipid accumulation, mitochondrial disarrangement, compared their controls. On other hand, overexpression improved systolic diastolic ameliorated hypertrophy fibrosis heart. Adeno-associated 9-USP28 also less storage, reduced reactive oxygen species formation, impairment tissues than 9-null As result, attenuated remodeling These results confirmed cell–derived cardiomyocytes. assays, pull-down assay mechanistically revealed directly interacted PPARα (peroxisome proliferator–activated receptor α), deubiquitinating stabilizing (Lys152) promote Mfn2 (mitofusin 2) transcription, thereby impeding morphofunctional defects. However, such cardioprotective benefits largely abrogated deletion conditional loss-of-function Mfn2. CONCLUSIONS: Our findings provide USP28-modulated mitochondria homeostasis involves PPARα-Mfn2 axis hearts, suggesting activation or targeting represents strategy for

Language: Английский

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Fasting: From Physiology to Pathology

Advanced Science, Journal Year: 2023, Volume and Issue: 10(9)

Published: Feb. 3, 2023

Overnutrition is a risk factor for various human diseases, including neurodegenerative metabolic disorders, and cancers. Therefore, targeting overnutrition represents simple but attractive strategy the treatment of these increasing public health threats. Fasting as dietary intervention combating has been extensively studied. practiced millennia, only recently have its roles in molecular clock, gut microbiome, tissue homeostasis function emerged. can slow aging most species protect against These centuried unfading adventures explorations suggest that fasting potential to delay help prevent treat diseases while minimizing side effects caused by chronic interventions. In this review, recent animal studies concerning role underlying mechanism physiology pathology are summarized, therapeutic highlighted, combination pharmacological discussed new regimen diseases.

Language: Английский

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Orange-Emissive Carbon Dots with High Photostability for Mitochondrial Dynamics Tracking in Living Cells

ACS Sensors, Journal Year: 2023, Volume and Issue: 8(3), P. 1161 - 1172

Published: Feb. 16, 2023

Mitochondria play significant roles in maintaining a stable internal environment for cell metabolism. Hence, real-time monitoring of the dynamics mitochondria is essential further understanding mitochondria-related diseases. Fluorescent probes provide powerful tools visualizing dynamic processes. However, most mitochondria-targeted are derived from organic molecules with poor photostability, making long-term challenging. Herein, we design novel probe based on carbon dots high performance tracking. Considering that targeting ability CDs related to surface functional groups, which generally determined by reaction precursors, successfully constructed O-CDs emission at 565 nm through solvothermal treatment m-diethylaminophenol. The bright quantum yield 12.61%, mitochondria-targeting ability, and good stability. possess (12.61%), specific outstanding optical Owing abundant hydroxyl ammonium cations surface, showed obvious accumulation colocalization coefficient up 0.90 remained steady even after fixation. Besides, compatibility photostability under various interruptions or long-time irradiation. Therefore, preferable tracking mitochondrial behavior live cells. We first observed fission fusion behaviors HeLa cells, then, size, morphology, distribution physiological pathological conditions were clearly recorded. More importantly, different interactions between lipid droplets during apoptosis mitophagy This study provides potential tool exploring other organelles, promoting research

Language: Английский

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