Multifunctional oligomer incorporation: a potent strategy to enhance the transfection activity of poly(l-lysine).

Natural polycations, such as poly(l-lysine) (PLL) and chitosan (CS), have inherent superiority as non-viral vectors due to their unparalleled biocompatibility and biodegradability. However, the application was constrained by poor transfection efficiency and safety concerns. Since previous modification strategies greatly weakened the inherent advantages of natural polycations, developing a strategy for functional group introduction with broad applicability to enhance the transfection efficiency of natural polycations without compromising their cationic properties is imperative. Herein, two uncharged functional diblock oligomers P(DMAEL-b-NIPAM) and P(DMAEL-b-Vlm) were prepared from a lactose derivative, N-iso-propyl acrylamide (NIPAM) as well as 1-vinylimidazole (Vlm) and further functionalized with four small ligands folate, glutathione, cysteine and arginine, respectively, aiming to enhance the interactions of complexes with cells, which were quantified utilizing a quartz crystal microbalance (QCM) biosensor, circumventing the tedious material screening process of cell transfection. Upon incorporation with PLL and DNA, the multifunctional oligomers endow the formulated ternary complexes with great properties suitable for transfection, such as anti-aggregation in serum, destabilized endosome membrane, numerous functional sites for promoted endocytosis and therefore robust transfection activity. Furthermore, different from the conventional strategy of decreasing cytotoxicity by reducing the charge density, the multifunctional oligomer incorporation strategy maintains the highly positive charge density, which is essential for efficient cellular uptake. This system develops a new platform to modify natural polycations towards clinical gene therapy.

Assessment of urinary kidney injury molecule-1 and interleukin-18 in the early post-burn period to predict acute kidney injury for various degrees of burn injury.

BACKGROUND: Burn patients with AKI have a higher mortality, rapid diagnosis and early treatment of AKI are necessary. Recent studies have demonstrated that urinary KIM-1 and IL-18 are potential biomarkers of early-stage AKI, however, changes in urinary KIM-1 and IL-18 levels are unclear in patients with burns. The aim of our study was to determine whether combined KIM-1 and IL-18 are more sensitive than traditional markers in detecting kidney injury in patients with burns. METHODS: Ninety-five burn patients hospitalized at the Burns and Plastic Surgery Center of our hospital from April 2013 to September 2013 were enrolled into this prospective study and divided into mild- (n = 37), moderate- (n = 30) and severe-burn groups (n = 28) by burn injury surface area. In the moderate- and severe-burn groups, patients were subcategorized to either the acute kidney injury (AKI) group, in which serum creatinine (Scr) increased to ≥ 26.5 µmol/L within 48 h, or the non-AKI group. Fifteen healthy subjects were selected as a control group. Blood specimens were collected to determine blood urea nitrogen (BUN), Scr, and other biochemical indicators. Urine samples collected at admission and 48 h after admission were analyzed for KIM-1 and IL-18. Correlations among urinary KIM-1 and IL-18, burn degree, and clinical biochemical indicators were investigated. RESULTS: AKI occurred in 11.2 % of burn patients (none in the mild-burn group). AKI developed 48 h after admission in 10.0 % of the moderate- and 28.6 % of the severe-burn groups. Urinary KIM-1 concentration in the moderate- and severe-burn groups was significantly higher than that in the control group; urinary IL-18 concentrations did not differ significantly among the burn and control groups. The AKI group had significantly higher concentrations of urinary KIM-1 and IL-18 than the non-AKI group, both at admission (p = 0.001 and p < 0.001, respectively) and 48 h later (p = 0.001 and p < 0.001, respectively). Both urinary KIM-1 and IL-18 increased before Scr. Receiver operating-curve (ROC) analysis demonstrated that KIM-1 combined with IL-18 predicted AKI with 72.7 % sensitivity and 92.8 % specificity. The area under the ROC curve was 0.904. CONCLUSIONS: Our results suggest that urinary KIM-1 and IL-18 may be used as early, sensitive indicators of AKI in patients with burns of varying degrees and provide clinical clues that can be used in early prevention of AKI.

Significance of vascular endothelial growth factor expression in renal tissue of patients with preeclamptic nephropathy.

OBJECTIVE: It was the aim of this study to evaluate the distribution and expression of vascular endothelial growth factor (VEGF) in kidneys of patients with preeclamptic nephropathy and their relationship with clinical and pathological manifestations. METHODS: From May 1993 to August 2004, 19 patients with a mean age of 28.1 +/- 4.53 years (range 23-40), diagnosed with preeclamptic nephropathy by renal biopsy, were enrolled in this study. Fifteen were nulliparous and 4 multipara. Their renal tissues were subjected to immunohistochemical staining by a four-layer peroxidase-antiperoxidase method using monoclonal anti-VEGF. Residual normal renal tissue obtained at nephrectomy served as control. The relationship between the expression pattern of VEGF and clinicopathological features was also investigated. RESULTS: The expression of VEGF markedly increased in renal tissues of patients with preeclamptic nephropathy at the early stage of gestation termination in comparison with normal controls. However, over time, it gradually decreased and reached the level of normal controls (100 vs. 71.43 vs. 20%, p < 0.05). The degree of endothelial proliferation in the glomeruli was closely related to the expression of VEGF, which was stronger in patients with diffuse endothelial proliferation than in those with segment proliferation (p < 0.05). In addition, there was a proportional relationship between the expression of VEGF and the level of urinary protein excretion (p < 0.05). CONCLUSION: The patients with preeclamptic nephropathy showed strong expressions of VEGF in glomeruli, which were closely associated with glomerular endothelial lesions and proteinuria, and over time, gradually weakened to normal level after gestation termination.