Obesity develops through progressive metabolic alterations that arise long before overt disease, highlighting the need for pharmacological strategies capable of targeting the earliest tissue adaptations to fat nutrient excess. Skeletal muscle plays a central role in systemic metabolic homeostasis and is among the first organs affected by high-fat diet (HFD) exposure. Oleoylethanolamide (OEA), a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, exerts broad metabolic actions in obesity, yet its impact on early skeletal muscle remodeling remains unknown. We investigated whether OEA could intercept the initial metabolic adaptations induced by HFD exposure in young rats. Male rats were exposed to HFD for seven weeks and treated with OEA (10mg/kg, i.p.) during the final two weeks. Short-term HFD induced a coordinated remodeling of skeletal muscle characterized by lipid accumulation, suppression of the PPAR-α/CPT-1 axis, altered mitochondrial and redox homeostasis, extracellular matrix remodeling, impaired myogenic signaling, and a shift toward a glycolytic contractile program despite only modest body-weight gain. OEA largely attenuated such alterations, preserving skeletal muscle metabolic and structural homeostasis through coordinated improvement of lipid oxidative metabolism, mitochondrial energetic status, and tissue remodeling. These findings identify skeletal muscle as an early target of fat-induced metabolic dysfunction and support further investigation of OEA as a promising pharmacological strategy to intercept obesity-associated metabolic deterioration before overt obesity develops.
M. Friuli, B. Eramo, Nisha Zahid et al.· Pharmacological Research· 0 citations
Nanomedicine has reshaped healthcare, especially in targeted drug delivery systems (DDSs) and diagnostics, addressing the limitations of traditional cancer therapies. Integration of photodynamic therapy (PDT) with nanoparticle‐based DDSs has significantly improved the targeted accumulation and pharmacokinetic properties of photosensitizers within tumor cells, enabling selective tumor cell death while sparing healthy tissues. This study developed chitosan‐sericin polyelectrolyte nanoparticles (CSSN NPs) via the Flash nanocomplexation (FNC) technique to enhance the 5‐aminolevulinic acid (5‐ALA) delivery, a precursor of protoporphyrin IX (PpIX), and evaluated their potential in PDT against the MCF‐7 breast cancer cell line. The 5‐ALA‐loaded CSSN NPs exhibited a hydrodynamic diameter ≤100 nm, a positive surface charge, and an encapsulation efficiency of ∼92% with a controlled release profile in acidic environments. In vitro assays demonstrated a ∼40% reduction in cell viability compared with free 5‐ALA, further confirmed by elevated red fluorescence observed in the Calcein/Propidium iodide assay. Confocal microscopy revealed strong PpIX red fluorescence and increased perinuclear accumulation, indicating effective cellular uptake. PpIX phototoxicity was validated by reactive oxygen species induction upon irradiation. These innovative biopolymer‐based DDSs demonstrate considerable potential in enhancing the therapeutic efficacy of 5‐ALA and improving PDT outcomes, setting the stage for future advancements in targeted cancer therapies.
Athira Narayanan, Benedetta di Chiara Stanca, Daniela Pinheiro et al.· Visual Information Expert Wo...· 0 citations
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