Results 61 to 70 of about 3,384,133 (256)

Unraveling 4‐Phenylbutyrate's Therapeutic Role in SLC6A1 Disorders: Pharmacochaperoning Over HDAC Inhibition

open access: yesAnnals of Clinical and Translational Neurology, EarlyView.
ABSTRACT Objective Variants in SLC6A1, encoding the GABA transporter 1 (GAT‐1), cause epilepsy, autism spectrum disorder, and developmental delay via loss of GABA uptake, impaired trafficking, and ER retention. We previously found that 4‐Phenylbutyrate (PBA), an FDA‐approved drug, restores GABA uptake and reduces seizures in SLC6A1‐related disorders ...
Melissa B. DeLeeuw   +5 more
wiley   +1 more source

Marine-derived chromopeptide A, a novel class I HDAC inhibitor, suppresses human prostate cancer cell proliferation and migration

open access: yesActa Pharmacologica Sinica, 2017
Histone deacetylases (HDACs), especially HDAC1, 2, 3 and 4, are abundantly expressed and over-activated in prostate cancer that is correlated with the poor prognosis.
Jingya Sun   +11 more
semanticscholar   +1 more source

Spatiotemporal Sequential Delivery of Chidamide Regulates Macrophage Reprogramming in Lymphoma Microenvironment Through HDACs‐STAT3 Pathway

open access: yesAdvanced Science, EarlyView.
Our study identifies the HDACs‐STAT3 axis as key regulator for M2 macrophage accumulation in DLBCL. We developed Chid@M2pep‐EVs/TP, a pH‐responsive drug delivery system for M2 macrophage specific chidamide administration. By coupling M2‐targeted chidamide with EVs‐mediated delivery, this system reprograms M2 to M1 via HDAC inhibition and STAT3 ...
Bo Dai   +15 more
wiley   +1 more source

GATA4‐Driven Transcription of HtrA1 Promotes Cellular Senescence in Ménière's Disease and Age‐Related Audio‐Vestibular Dysfunction

open access: yesAdvanced Science, EarlyView.
This study identifies the HDAC6/GATA4/HtrA1 axis as a critical driver of cellular senescence in the inner ear. GATA4 nuclear translocation, facilitated by HDAC6 downregulation, transcriptionally activates HtrA1, promoting hair cell senescence, SASP, and audio‐vestibular dysfunction in models of Ménière's disease and age‐related audio‐vestibular ...
Na Zhang   +16 more
wiley   +1 more source

LC3B Mediated SETDB1‐Accounted Alcoholic Steatohepatitis via Lipidation‐Dependent LAP and Lipidation‐Independent Nuclear Stabilization

open access: yesAdvanced Science, EarlyView.
SETDB1 is progressively downregulated in ALD, correlating with disease severity. SETDB1 deficiency impairs LAP by disrupting Rubicon membrane localization, leading to defective lipid droplet clearance. Concurrently, loss of SETDB1 reduces nuclear LC3B, causing R‐loop accumulation and cGAS‐STING‐driven inflammation. Lipidated LC3B mediates LAP‐dependent
Yi Zhang   +17 more
wiley   +1 more source

Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy

open access: yesAdvanced Science, EarlyView.
Lactate, once deemed a metabolic waste, emerges as a central regulator of cancer progression. This review elucidates how lactate and its epigenetic derivative, protein lactylation, orchestrate tumor metabolism, immune suppression, and therapeutic resistance.
Jiajing Gong   +5 more
wiley   +1 more source

Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines

open access: yesTargeted oncology, 2016
BackgroundTargeting of class I histone deacetylases (HDACs) exerts antineoplastic actions in various cancer types by modulation of transcription, upregulation of tumor suppressors, induction of cell cycle arrest, replication stress and promotion of ...
Maria Pinkerneil   +4 more
semanticscholar   +1 more source

Understanding and Overcoming Antibody‐Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer

open access: yesAdvanced Science, EarlyView.
Antibody–drug conjugates (ADCs) transform breast cancer therapy, yet resistance limits their durability. Emerging evidence reveals that ADC failure is not solely tumor‐intrinsic but shaped by dynamic tumor–microenvironment interactions that alter drug delivery, processing, and response.
Minji Seo, Jangsoon Lee, Naoto T. Ueno
wiley   +1 more source

Enhanced Glycolysis‐Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1

open access: yesAdvanced Science, EarlyView.
Neuronal PKM2‐driven glycolysis generates excess lactate that triggers histone H3K18 lactylation (H3K18la), establishing a pathogenic metabolic‐epigenetic axis in epilepsy. Elevated H3K18la enriches the Cop1 promoter, transcriptionally upregulating the E3 ubiquitin ligase COP1, which subsequently drives proteasomal degradation of GABAARβ2 and impairs ...
Yuan Meng   +8 more
wiley   +1 more source

HDAC inhibitor ITF2357 reduces resistance of mutant-KRAS non-small cell lung cancer to pemetrexed through a HDAC2/miR-130a-3p-dependent mechanism

open access: yesJournal of Translational Medicine, 2023
Background Histone deacetylases (HDAC) contribute to oncogenic program, pointing to their inhibitors as a potential strategy against cancers. We, thus, studied the mechanism of HDAC inhibitor ITF2357 in resistance of mutant (mut)-KRAS non-small cell lung
Jian Cui   +5 more
doaj   +1 more source

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