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Nitsa Buaron Antonella Mangraviti Francesco Volpin Ann Liu Mariangela Pedone Eric Sankey Dina Aranovich Itay Adar Fausto J. Rodriguez Abraham Nyska Riki Goldbart Tamar Traitel Henry Brem Betty Tyler Joseph Kost 《Advanced functional materials》2021,31(44):2100643
Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases. 相似文献
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Assuming that the chemical reactions used to synthesize a combinatorial library member are successful, then knowledge of the specific reaction sequence is equivalent to knowing the member's chemical identity. Because the determination of chemical identity is typically not automatable and requires a substantial amount of material, schemes that encode a member's reaction history onto the reaction platform are of value. The primary benefits of encoding are relational nomenclature (all methods) and automated handling (some methods). Encoding methods evaluated to date are spatial, graphical, chemical, spectrometric, electronic, and physical. 相似文献
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OBJECTIVES: To assess that neuromuscular relaxation onset of the adductor pollicis (AP) is related to neuromuscular stimulation rate. To assess that train-of-four (TOF) at 0.05 Hz is a more accurate indicator of optimal tracheal intubation time and conditions, than TOF at 0.08 Hz. STUDY DESIGN: Prospective, comparative, randomized double-blind study. PATIENTS: Forty adults, physical class ASA 1 or 2, undergoing general anaesthesia with tracheal intubation were allocated to two groups (n = 20) according to the sequence of stimulation of the AP: either TOF at 0.05 Hz (test group) or TOF at 0.08 Hz (control group). METHODS: Induction of anaesthesia was achieved with thiopentone, fentanyl and vecuronium (0.1 mg.kg-1). Neuromuscular monitoring was obtained with force displacement transducers attached to each AP. Tracheal intubation was performed once AP muscular response obtained with TOF at 0.05 Hz for test group and TOF at 0.08 Hz for control group was abolished. Results are expressed as mean +/- SEM. Fisher exact test was used for intubation conditions comparison. Curarization time between groups was compared with unpaired Student's t test (P < 0.05 accepted). RESULTS: TOF with 0.05 Hz stimulation significantly increased curarization time: 217 +/- 7 versus 162 +/- 6 s (P < 0.001). Intubation conditions were excellent in 95% and good in 5% of patients in the study group, compared to 15 and 40% in the control group, respectively (P < 0.01) in 45% of the control group patients coughing at intubation occurred. CONCLUSION: Low stimulation rate (TOF at 0.05 Hz) of AP is a reliable technique to determine the appropriate intubation time for patients paralyzed with vecuronium. 相似文献
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