Unveiling the Power of Gabapentin-Loaded Nanoceria with Multiple Therapeutic Capabilities for the Treatment of Dry Eye Disease

ACS Nano, Journal Year: 2023, Volume and Issue: 17(24), P. 25118 - 25135

Published: Dec. 5, 2023

Dry eye (DE) disease, which is primarily linked to aqueous deficiency, an escalating health issue worldwide, mainly due the widespread use of electronic devices. The major obstacles in DE pharmacotherapy include insufficient therapeutic efficacy and low ocular bioavailability. This study presents development a ceria-based nanosystem carry gabapentin (GBT), aiming offer comprehensive relief from symptoms. We prepared multifunctional nanoceria capped with thiolated gelatin followed by cross-linking glutaraldehyde, yielding nanocarrier desirable biocompatibility antioxidant, anti-inflammatory, antiangiogenic, antiapoptotic, neuronal protective activities. Specifically, highly abundant thiol groups on increased cellular uptake 2.3-fold its mucin-binding efficiency 10-fold, thereby extending retention amplifying activity. Moderate not only enhanced bioavailability but also provided slow, degradation-controlled release GBT promote lacrimal stimulation restore tear film. In rabbit model DE, topical administration our GBT/nanoceria nanoformulation resulted alleviation symptoms, including repairing corneal epithelial damage, preserving nerve density, stimulating secretion, demonstrating superior performance comparison free drug. These results underscore safety potential this innovative for pharmacotherapy.

Language: Английский

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Aquaporins: Gatekeepers of Fluid Dynamics in Traumatic Brain Injury

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6553 - 6553

Published: June 14, 2024

Aquaporins (AQPs), particularly AQP4, play a crucial role in regulating fluid dynamics the brain, impacting development and resolution of edema following traumatic brain injury (TBI). This review examines alterations AQP expression localization post-injury, exploring their effects on overall outcomes. We discuss underlying molecular mechanisms expression, highlighting potential therapeutic strategies to modulate function. These insights provide comprehensive understanding AQPs TBI suggest novel approaches for improving clinical outcomes through targeted interventions.

Language: Английский

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Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(1), P. 610 - 610

Published: Jan. 3, 2024

Sepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as 5 (Aqp5) knockdown provided enhanced sepsis survival in murine model. Potential AQP5 provide sulfonamides their derivatives. In this study, we tested hypothesis that reduce expression different conditions. The impact of on immune cell migration was examined lines REH RAW 264.7 qPCR, Western blot assay. Subsequently, whether furosemide methazolamide capable reducing after LPS incubation investigated whole blood samples healthy volunteers. Incubation with (10−5 M) (10−6 reduced mRNA protein about 30% cells. Pre-incubation cells towards SDF1-α compared non-preincubated control level. PBMCs led reduction LPS-induced levels, while failed it. Methazolamide appears However, administration, no longer possible. Hence, our study indicates has potential be used prophylaxis.

Language: Английский

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Aquaporins as Membrane Proteins: The Current Status

Frontiers in Bioscience-Scholar, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 20, 2025

Background: The ambient conditions that ensure the expected protein folding activity are important in directing process. Water favors formation of a centrally located hydrophobic nucleus with exposed polar residues for preferable contact water molecules. Different created by cell membrane, which also provides an environment proteins, including channels responsible transporting multiple molecules, concentration is controlled as part homeostasis. Aquaporins transmembrane proteins primarily and low-molecular-weight compounds. Methods: fuzzy oil drop (FOD) model was applied its modified form, FOD-M, analysis. FOD allows quantitative assessment structure adaptation to external conditions, ensuring biological activity. Results: aquaporins studied this work revealed adaptations stabilizing environments Conclusions: A significant degree similarity demonstrated human using FOD-M. This enabled function achieved through appropriate balance between micelle-like decomposition modification due specificity ensures adequate

Language: Английский

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Calycosin synergizes with methotrexate in the treatment of Sjögren’s disease by targeting BATF in T follicular helper cells

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Language: Английский

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AQP5 trafficking is regulated by its C-terminal tail and interaction with prolactin-inducible protein

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: April 16, 2025

Abstract Background Aquaporin-5 (AQP5) is a crucial membrane protein involved in water transport across cellular membranes, particularly within exocrine glands such as salivary glands. Dysregulation of AQP5, including its mislocalization, has been associated with various diseases, emphasizing the need to understand molecular mechanisms governing trafficking. This study investigates multifaceted regulatory AQP5 trafficking, specific emphasis on role carboxyl-terminal (C-terminal) tail and functional involvement prolactin-inducible (PIP) an interacting partner. Methods An innovative 2D-custom model employing SNAP-tag human constructs together novel automated algorithm-based methodology was used following immunofluorescence confocal microscopy assess hAQP5 localization plasma stably transfected normal gland-SV40 transformed-acinar cells (NS-SV-AC). The expression verified by Western blot analysis. Results SNAP-hAQP5 expressed NS-SV-AC allowed explore C-terminal hAQP5-hPIP interaction trafficking upon stimulation. use truncation revealed distinct responses intracellular 3’,5’-cyclic adenosine monophosphate (cAMP) calcium increase, shedding light importance regions highly flexible distal part for Furthermore, our investigation interplay between hPIP that PIP promotes translocation membrane, blunting effects calcium- cAMP-dependent pathways sub-cellular localization. Conclusion In summary, this advances understanding dynamics provides critical insights into roles PIP. sets stage future investigations identify individual amino acids phosphorylation sites C-terminus mechanism protein-protein interaction, dynamic process high resolution live cell imaging. Further research area warranted uncover regulation offering opportunities development therapeutic strategies.

Language: Английский

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Presenting the Special Issue “Aquaporins: Dynamic Role and Regulation”

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4384 - 4384

Published: May 5, 2025

Aquaporins (AQPs) were discovered in human erythrocytes 1987 by Peter Agree and collaborators [...]

Language: Английский

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Aquaporin Channels in Skin Physiology and Aging Pathophysiology: Investigating Their Role in Skin Function and the Hallmarks of Aging

Biology, Journal Year: 2024, Volume and Issue: 13(11), P. 862 - 862

Published: Oct. 24, 2024

This study examines the critical role of aquaporins (AQPs) in skin physiology and aging pathophysiology. The plays a vital maintaining homeostasis by acting as protective barrier against external pathogens excessive water loss, while also contributing to appearance self-esteem individuals. Key physiological features, such elasticity repair capability, are essential for its proper function. However, with aging, these characteristics deteriorate, reducing skin's ability tolerate environmental stressors which contribute well internal processes, negatively affect function, immune response, overall well-being. AQPs, primarily known facilitating transport, significant normal functions, including hydration movement molecules like glycerol hydrogen peroxide, influence various cellular processes functions. In this context, we categorized aquaporin dysfunction into several hallmarks mitochondrial dysfunction, senescence, stem cell depletion, impaired macroautophagy, dysbiosis, inflamm-aging. Eight (AQP1, 3, 5, 7, 8, 9, 10, 11) expressed cells, regulating migration, proliferation, differentiation, response. Dysregulation or altered expression proteins can enhance related pathologies activating hallmarks. provides valuable insights potential targeting mitigate improve physiologic

Language: Английский

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ARL13B controls male reproductive tract physiology through primary and Motile Cilia

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Oct. 14, 2024

ARL13B is a small regulatory GTPase that controls ciliary membrane composition in both motile cilia and non-motile primary cilia. In this study, we investigated the role of efferent ductules, tubules male reproductive tract essential to fertility which co-exist. We used genetically engineered mouse model delete Arl13b ductule epithelial cells, resulting compromised architecture functions. This deletion led disturbances reabsorptive/secretory processes triggered an inflammatory response. The observed phenotype showed significant variability linked partial infertility, highlighting importance maintaining proper physiological balance these ducts. These results emphasize dual functions regulating duct homeostasis, offering deeper insights into how related diseases affect system. disrupts structure leading impaired inflammation, subfertility. highlights ARL13B's critical physiology.

Language: Английский

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Modulation of Membrane Trafficking of AQP5 in the Lens in Response to Changes in Zonular Tension Is Mediated by the Mechanosensitive Channel TRPV1

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 9080 - 9080

Published: May 22, 2023

In mice, the contraction of ciliary muscle via administration pilocarpine reduces zonular tension applied to lens and activates TRPV1-mediated arm a dual feedback system that regulates lens' hydrostatic pressure gradient. rat lens, this pilocarpine-induced reduction in also causes water channel AQP5 be removed from membranes fiber cells located anterior influx equatorial efflux zones. Here, we determined whether membrane trafficking is regulated by activation TRPV1. Using microelectrode-based methods measure surface pressure, found increased lenses TRPV1, while removal observed using immunolabelling was abolished pre-incubation with TRPV1 inhibitor. contrast, mimicking actions blocking TRPV4 then activating resulted sustained increase These results show response decrease mediated suggest regional changes PH2O contribute gradient regulation.

Language: Английский

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