Age-related macular degeneration (AMD) is the main cause of blurred vision, and oxidative stress is a leading risk factor for AMD pathology. Small extracellular vesicles (EVs) are 50-90 nm membrane microvesicles (MVs) released by several cell types in a controlled fashion and they transfer from cell to cell to mediate disease progression. EVs encapsulate and transfer microRNAs (miRNA) to recipient cells. MiRNAs are small non-coding RNA molecules that inhibit expression and function of targeted mRNAs through miRNA/mRNA interactions in the conserved 3'UTR regions, and in this way they can modulate a variety of physiological and pathological processes. Dysregulation of EVs and their miRNAs cargo from retinal cells is believed to be correlated to a loss of cellular homeostasis and AMD pathology. This review investigates the association between oxidative stress, sEVs, miRNAs, and AMD pathogenesis, and the potential for discovering novel treatment targets for AMD.
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Nat Commun
December 2024
Department of Ophthalmology, Columbia University, New York, NY, USA.
Best1 and Best2 are two members of the bestrophin family of anion channels critically involved in the prevention of retinal degeneration and maintenance of intraocular pressure, respectively. Here, we solved glutamate- and γ-aminobutyric acid (GABA)-bound Best2 structures, which delineate an intracellular glutamate binding site and an extracellular GABA binding site on Best2, respectively, identified extracellular GABA as a permeable activator of Best2, and elucidated the co-regulation of Best2 by glutamate, GABA and glutamine synthetase in vivo. We further identified multiple small molecules as activators of the bestrophin channels.
View Article and Find Full Text PDFCytojournal
November 2024
Medical College, Ningbo University Health Science Center, Ningbo, China.
Objective: Patients with non-small cell lung cancer (NSCLC) have poor prognoses. Sulfatase 1 (SULF1) is an extracellular neutral sulfatase and is involved in multiple physiological processes. Hence, this study investigated the function and possible mechanisms of SULF1 in NSCLC.
View Article and Find Full Text PDFAdv Rheumatol
December 2024
Department of Rehabilitation Medicine, Wuhan No.1 Hospital, 215 Zhongshan Avenue, Qiaokou District, Wuhan, Hubei, 430022, China.
Background: Osteoarthritis (OA) is a common degenerative joint disease. Circular RNA Phosphodiesterase 1 C (circ-PDE1C, hsa_circ_0134111) has participated in the IL-1β-induced chondrocyte damages. The objective of our study was to explore the molecular mechanism of circ-PDE1C.
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December 2024
German Center for Neurodegenerative Diseases (LMU), Klinikum, Germany.
Background: The prion-like spreading of Tau pathology is the leading cause of disease progression in various tauopathies. A critical step in propagating pathologic Tau in the brain is the transport from the extracellular environment and accumulation inside naïve neurons. Current research indicates that human neurons internalize both the physiological extracellular Tau (eTau) monomers and the pathological eTau aggregates.
View Article and Find Full Text PDFBioact Mater
April 2025
Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stom, Shanghai, 200011, China.
Angiogenesis is imperative for bone regeneration, yet the conventional cytokine therapies have been constrained by prohibitive costs and safety apprehensions. It is urgent to develop a safer and more efficient therapeutic alternative. Herein, utilizing the methodologies of Deep Learning (DL) and Natural Language Processing (NLP), we proposed a paradigm algorithm that amalgamates with a variant, , to deftly discern potential pro-angiogenic peptides from intrinsically disordered regions (IDRs) of 262 related proteins, where are fertile grounds for developing safer and highly promising bioactive peptides.
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