Chronic alcohol consumption is a major cause of liver injury, progressing from hepatic steatosis to inflammation, necrosis, and fibrosis. Protein kinase C epsilon (PRKCε) has been implicated in alcohol-induced hepatic steatosis; however, its contribution to subsequent inflammatory and necrotic injury remains unclear. The present study investigated the differential role of PRKCε in chronic ethanol-induced liver injury using an experimental animal model. Mice were maintained on a high-fat diet and treated with either saline or PRKCε antisense oligonucleotides (ASO) for four weeks, followed by ethanol exposure. Hepatic lipid accumulation, fatty acid synthase (FAS), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), inflammation, necrosis, and fibrin deposition were evaluated. PRKCε ASO treatment significantly attenuated ethanol-induced hepatic lipid accumulation and prevented the ethanol-mediated increase in FAS expression. Furthermore, PRKCε inhibition completely suppressed the elevation of TNF-α expression associated with ethanol exposure. Despite these effects, PRKCε ASO administration did not significantly reduce chronic ethanol-induced hepatic inflammation or necrosis. Similarly, the ethanol-induced upregulation of PAI-1 and accumulation of fibrin were unaffected by PRKCε inhibition. These findings indicate that PRKCε plays an important role in alcohol-induced hepatic steatosis and associated metabolic alterations but is not the primary mediator of chronic inflammatory and necrotic liver injury. The persistence of PAI-1 elevation and fibrin deposition despite PRKCε inhibition suggests that these pathways may independently contribute to progression of alcohol-induced hepatic damage. Thus, targeting multiple pathological pathways may provide a more effective strategy for preventing chronic alcohol-related liver injury.
Aditi Jyotishi, V. Chauhan, S. Jain et al.· Adolescência e Saúde· 0 citations
Background: Psoriasis is a chronic inflammatory skin disease that severely impacts patients' quality of life. Traditional topical deliveries of salicylic acid (SA) often cause localized irritation and face systemic limitations due to the formidable barrier properties.
Objective: This study aimed to formulate, optimize, and evaluate an ultra-deformable vesicular carrier system—transfersomes—incorporated into a carbopol hydrogel base for the sustained and enhanced topical delivery of salicylic acid.
Methods: Salicylic acid-loaded transfersomes were prepared via the thin-film hydration technique utilizing Soya-phosphatidylcholine (PC) and Span 80 in varying ratios. The prepared vesicles were characterized for particle size, zeta potential, and entrapment efficiency (%EE). The optimized formulation (TF4) was successfully incorporated into three different concentrations of Carbopol 934 gel bases (0.5%, 1.0%, and 2.0% w/w). The hydrogels were extensively evaluated for their organoleptic parameters, pH, viscosity, spreadability, drug content, and in-vitro drug diffusion kinetics via a modified Franz diffusion cell over 14 hours.
Results: The vesicle sizes of the prepared transfersomes ranged from 161.08 nm to 552.8 nm with an encapsulation efficiency between 63.70% and 90.89%. The optimized formulation, TF4, presented a vesicle size of 269.00 nm, high entrapment efficiency of 73.70%, and a stable zeta potential of -35.6 mV. The formulated hydrogels displayed excellent homogeneity and acceptable pH ranges (6.9 to 7.3). In-vitro diffusion profiling revealed that formulation TF2 (1.0% w/w Carbopol) exhibited the most balanced, controlled release profile, reaching 94.08% drug delivery at the end of 14 hours. Mathematical modeling demonstrated compliance with zero-order kinetics and a non-Fickian anomalous transport mechanism (0.5 < n < 1.0).
Conclusion: The developed transfersomal hydrogel serves as an advanced, highly elastic vesicular platform that effectively bypasses the skin barrier, offering sustained release while potentially reducing the localized toxicity associated with standard salicylic acid treatments.
Adarsh Jedhe, Neelima Naneriya, S. Jain et al.· International journal of pha...· 0 citations
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