Correction: Characterization of chitosan- and ß-cyclodextrin-modified forms of magnesium-doped hydroxyapatites as enhanced carriers for levofloxacin: loading, release, and anti-inflammatory properties.

[This corrects the article DOI: 10.1039/D4RA02144D.].

Characterization of chitosan- and ß-cyclodextrin-modified forms of magnesium-doped hydroxyapatites as enhanced carriers for levofloxacin: loading, release, and anti-inflammatory properties.

An advanced form of magnesium-rich hydroxyapatite (Mg·HAP) was modified with two types of biopolymers, namely chitosan (CH/Mg·HAP) and ß-cyclodextrin (CD/Mg·HAP), producing two types of bio-composites. The synthesized materials were developed as enhanced carriers for levofloxacin to control its loading, release, and anti-inflammatory properties. The polymeric modification significantly improved the loading efficiency to 281.4 mg g-1 for CH/Mg·HAP and 332.4 mg g-1 for CD/Mg·HAP compared with 218.3 mg g-1 for Mg·HAP. The loading behaviors were determined using conventional kinetic and isotherm models and mathematical parameters of new equilibrium models (the monolayer model of one energy). The estimated density of effective loading sites (Nm (LVX) = 88.03 mg g-1 (Mg·HAP), 115.8 mg g-1 (CH/Mg·HAP), and 138.5 mg g-1 (CD/Mg·HAP)) illustrates the markedly higher loading performance of the modified forms of Mg·HAP. Moreover, the loading energies (<40 kJ mol-1) in conjunction with the capacity of each loading site (n > 1) and Gaussian energies (<8 kJ mol-1) signify the physical trapping of LVX molecules in vertical orientation. The addressed materials validate prolonged and continuous release behaviors. These behaviors accelerated after the modification procedures, as the complete release was identified after 160 h (CH/Mg·HAP) and 200 h (CD/Mg·HAP). The releasing behaviors are regulated by both diffusion and erosion mechanisms, according to the kinetic investigations and diffusion exponent analysis (>0.45). The entrapping of LVX into Mg·HAP induces its anti-inflammatory properties against the generation of cytokines (IL-6 and IL-8) in human bronchial epithelia cells (NL20), and this effect displays further enhancement after the integration of chitosan and ß-cyclodextrin.

Profiling the Hsp70 Chaperone Network in Heat-Induced Proteotoxic Stress Models of Human Neurons.

Heat stroke is among the most hazardous hyperthermia-related illnesses and an emerging threat to humans from climate change. Acute brain injury and long-lasting brain damage are the hallmarks of this condition. Hyperthermic neurological manifestations are remarkable for their damage correlation with stress amplitude and long-term persistence. Hyperthermia-induced protein unfolding, and nonspecific aggregation accumulation have neurotoxic effects and contribute to the pathogenesis of brain damage in heat stroke. Therefore, we generated heat-induced, dose-responsive extreme and mild proteotoxic stress models in medulloblastoma [Daoy] and neuroblastoma [SH-SY5Y] and differentiated SH-SY5Y neuronal cells. We show that heat-induced protein aggregation is associated with reduced cell proliferation and viability. Higher protein aggregation in differentiated neurons than in neuroblastoma precursors suggests a differential neuronal vulnerability to heat. We characterized the neuronal heat shock response through RT-PCR array analysis of eighty-four genes involved in protein folding and protein quality control (PQC). We identify seventeen significantly expressed genes, five of which are Hsp70 chaperones, and four of their known complementing function proteins. Protein expression analysis determined the individual differential contribution of the five Hsp70 chaperones to the proteotoxic stress response and the significance of only two members under mild conditions. The co-expression analysis reveals significantly high co-expression between the Hsp70 chaperones and their interacting partners. The findings of this study lend support to the hypothesis that hyperthermia-induced proteotoxicity may underlie the brain injury of heat stroke. Additionally, this study presents a comprehensive map of the Hsp70 network in these models with potential clinical and translational implications.