(2015) Influence of phospholipid types and animal models on the accelerated blood clearance phenomenon of PEGylated liposomes upon repeated injection, Drug Delivery, 22:5, 598-607, DOI: 10.3109/10717544.2014 AbstractWhen polyethylene glycol (PEG)ylated liposomes were repeatedly injected into the same animal, the second dose of liposomes would rapidly clear from the bloodstream and enhance accumulation in the liver and spleen, and this phenomenon is called ''accelerated blood clearance (ABC)''. There are many factors known to influence ABC phenomenon, in this study, we mainly focused on the effects of different phospholipids (PL) types and animal models. The effects of PL types on ABC phenomenon were examined by repeating injection of PEGylated liposomes prepared by five different types of PL (hydrogenated soy phosphatidylcholine, egg sphingomyelin, soybean phosphatidycholin, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and egg phosphatidycholin) in rats. Dramatically, repeated injection of different types of PL could induce ABC phenomenon altogether. Both t 1/2 and AUC of experimental group (EG) were lower significantly than those of control group (CG). Our results also showed that the liver accumulation of second dose increased significantly (p50.01) in all EG as compared that of CG. Interestingly, ABC phenomenon of liposomes prepared by unsaturated PL was more obvious than that of saturated PL. All the first dose could induce the antibody (anti-PEG IgM) level increasing significantly (p50.01). For different animal models, we found that after repeated injection of PEGylated liposomes, rats, mice, rabbits and guinea pigs could produce ABC phenomenon. Various PL types and animal models could all produce the ABC phenomenon. However, their extent of accelerated clearance differed. ABC phenomenon is possibly a ubiquitous immune phenomenon in life.

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PURPOSE. Corneal ulcers are a common eye inflammatory disease that can cause visual impairment or even blindness if not treated promptly. Ocular trauma is a major risk factor for corneal ulcers, and corneal trauma in agricultural work can rapidly progress to corneal ulcers. This study aims to evaluate the changes in the ocular surface (OS) microbiome of patients with traumatic corneal ulcer (TCU). METHODS. Among 20 healthy control (HC) subjects and 22 patients with TCU, 42 eyes were examined to investigate the OS microbial flora using metagenomic shotgun sequencing. RESULTS. At the taxonomic composition level, our findings showed that dysbiosis (alterations in richness and community structure) occurs in the OS microbiome of patients with TCU. Notably, Pseudomonas was present at a greater than 30% relative abundance in all individuals in the TCU group. At the species level, the abundance of Pseudomonas fluorescens and Pseudomonas aeruginosa was significantly elevated in the TCU group compared to the HC group. At the functional level, we identified significant differences in the HC and TCU groups. We observed that inflammation-related pathways involved in bacterial chemotaxis, flagellar assembly, and biofilm formation were significantly more abundant in the TCU group. Besides, the pathways related to biosynthesis, degradation, and metabolism were also increased significantly in the TCU group. CONCLUSIONS. These findings indicate an altered OS microbiome in the affected eyes of patients with TCU. Further research is needed to determine whether these alterations contribute to the pathogenesis of TCU or impact disease progression.

The application of glucose-mannitol composite lyoprotectants can obtain a good G-Rg3 lyophilized preparation.

The marine bacterium Vibrio vulnificus causes potentially fatal bloodstream infections, typically in patients with chronic liver diseases. The inflammatory response and antibacterial function of phagocytes are crucial for limiting bacterial infection in the human hosts. How V. vulnificus affects macrophages after phagocytosis is unclear. In this report, we found that the bactericidal activity of macrophages to internalize V. vulnificus was dependent on mammalian target of rapamycin (mTOR) and NODlike receptor (NLR) family pyrin domain containing 3 (NLRP3) interaction. Additionally, the NLRP3 expression was dependent on mTORC1 activation. Inhibited mTORC1 or absence of NLRP3 in macrophages impaired V. vulnificus-induced phagosome acidification and phagolysosome formation, leading to a reduction of intracellular bacterial clearance. mTORC1 signaling overactivation could increase NLRP3 expression and restore insufficient phagosome acidification. Together, these findings indicate that the intracellular bactericidal activity of macrophages responding to V. vulnificus infection is tightly controlled by the crosstalk of NLRP3 and mTOR and provide critical insight into the host bactericidal activity basis of clearance of V. vulnificus through lyso/phagosome.