Image_2_MRI-Based Demonstration of the Normal Glymphatic System in a Human Population: A Systematic Review.TIF

BackgroundThe glymphatic system has been described as one that facilitates the exchange between the cerebrospinal fluid (CSF) and interstitial fluid, and many recent studies have demonstrated glymphatic flow based on magnetic resonance imaging (MRI). We aim to systematically review the studies demonstrating a normal glymphatic flow in a human population using MRI and to propose a detailed glymphatic imaging protocol.MethodsWe searched the MEDLINE and EMBASE databases to identify studies with human participants involving MRI-based demonstrations of the normal glymphatic flow. We extracted data on the imaging sequence, imaging protocol, and the targeted anatomical structures on each study.ResultsAccording to contrast-enhanced MRI studies, peak enhancement was sequentially detected first in the CSF space, followed by the brain parenchyma, the meningeal lymphatic vessel (MLV), and, finally, the cervical lymph nodes, corresponding with glymphatic flow and explaining the drainage into the MLV. Non-contrast flow-sensitive MRI studies revealed similar glymphatic inflow from the CSF space to the brain parenchyma and efflux of exchanged fluid from the brain parenchyma to the MLV.ConclusionWe may recommend T1-weighted contrast-enhanced MRI for visualizing glymphatic flow. Our result can increase understanding of the glymphatic system and may lay the groundwork for establishing central nervous system fluid dynamic theories and developing standardized imaging protocols.</p

Image_1_MRI-Based Demonstration of the Normal Glymphatic System in a Human Population: A Systematic Review.TIF

BackgroundThe glymphatic system has been described as one that facilitates the exchange between the cerebrospinal fluid (CSF) and interstitial fluid, and many recent studies have demonstrated glymphatic flow based on magnetic resonance imaging (MRI). We aim to systematically review the studies demonstrating a normal glymphatic flow in a human population using MRI and to propose a detailed glymphatic imaging protocol.MethodsWe searched the MEDLINE and EMBASE databases to identify studies with human participants involving MRI-based demonstrations of the normal glymphatic flow. We extracted data on the imaging sequence, imaging protocol, and the targeted anatomical structures on each study.ResultsAccording to contrast-enhanced MRI studies, peak enhancement was sequentially detected first in the CSF space, followed by the brain parenchyma, the meningeal lymphatic vessel (MLV), and, finally, the cervical lymph nodes, corresponding with glymphatic flow and explaining the drainage into the MLV. Non-contrast flow-sensitive MRI studies revealed similar glymphatic inflow from the CSF space to the brain parenchyma and efflux of exchanged fluid from the brain parenchyma to the MLV.ConclusionWe may recommend T1-weighted contrast-enhanced MRI for visualizing glymphatic flow. Our result can increase understanding of the glymphatic system and may lay the groundwork for establishing central nervous system fluid dynamic theories and developing standardized imaging protocols.</p

pH-Responsive Charge-Conversional Poly(ethylene imine)–Poly(l‑lysine)–Poly(l‑glutamic acid) with Self-Assembly and Endosome Buffering Ability for Gene Delivery Systems

Poly­(ethylene imine)–poly­(l-lysine)–poly­(l-glutamic acid) (PKE) polymers with various glutamic acid portions were synthesized by ring opening polymerization of l-lysine N-carboxyanhydride (NCA) and l-glutamic acid NCA from poly­(ethylene imine) 1.8 kDa (PEI1.8k) as a macroinitiator. It was found that their glutamic acid residues could buffer endosomal pH. PK5E9 polymer could form nanoparticles by self-assembly and nanosized polyplexes, possessing pH-responsive charge-conversion properties. PK5E9 or its polyplex nanoparticles showed polyhedral structures with bumpy surfaces. Its cytotoxicity was marginal at both pH 7.4 and 6.0, and its transfection efficiency was highly increased at pH 6.0. The improved transfection efficiency in acidic conditions was thought to be induced by elevated cellular uptake of the polyplexes via charge-conversion from negative to positive charges. Its transfection was also found to be mediated by endosomal escape through endosome buffering by bafilomycin A1-treated transfection. In conclusion, PK5E9 polymer with self-assembly and endosome buffering ability was found to possess potentials for efficient gene delivery systems in acidic conditions via charge conversion, which may be applied for tumor microenvironment-targeting

Manufacturing Process Development of Tegoprazan as a Potassium-Competitive Acid Blocker (P-CAB)

Tegoprazan, a selective potassium-competitive acid blocker, was approved in 2018 in the Republic of Korea for the treatment of gastroesophageal reflux disease (GERD), erosive esophagitis (EE), and nonerosive reflux disease (NERD). The complexity of tegoprazan, which contains a 4,6-disubstituted 1H-benzo[d]imidazole core and a chiral chromanol moiety, makes it a challenging molecule to prepare on a commercial scale. An efficient and economical route of the key intermediates and a much improved end-game for tegoprazan were developed