Therapeutic efficiency of folated poly(ethylene glycol)-chitosan-graft-polyethylenimine-Pdcd4 complexes in H-ras12V mice with liver cancer

BACKGROUND: Chitosan and chitosan derivatives have been proposed as alternative and biocompatible cationic polymers for nonviral gene delivery. However, the low transfection efficiency and low specificity of chitosan is an aspect of this approach that must be addressed prior to any clinical application. In the present study, folated poly(ethylene glycol)-chitosan-graft-polyethylenimine (FPCP) was investigated as a potential folate receptor-overexpressed cancer cell targeting gene carrier. METHODS: The FPCP copolymer was synthesized in two steps. In the first step, folate-PEG was synthesized by an amide formation reaction between the activated carboxyl groups of folic acid and the amine groups of bifunctional poly(ethylene glycol) (PEG). In the second step, FPCP was synthesized by an amide formation reaction between the activated carboxyl groups of folate-PEG and amine groups of CHI-g-polyethyleneimine (PEI). The composition of FPCP was characterized by 1H nuclear magnetic resonance. RESULTS: FPCP showed low cytotoxicity in various cell lines, and FPCP-DNA complexes showed good cancer cell specificity as well as good transfection efficiency in the presence of serum. Further, FPCP-Pdcd4 complexes reduced tumor numbers and progression more effectively than PEI 25 kDa in H-ras12V liver cancer mice after intravenous administration. CONCLUSION: Our data suggest that FPCP, which has improved transfection efficiency and cancer cell specificity, may be useful in gene therapy for liver cancer

Pullulan Nanoparticles as Prebiotics Enhance the Antibacterial Properties of Lactobacillus plantarum Through the Induction of Mild Stress in Probiotics

Synbiotics, which are the combination of probiotics and prebiotics, have recently attracted attention because of their synergistic net health benefits. Probiotics have been used as alternatives to antibiotics. Among the probiotics, Lactobacillus plantarum (LP) has shown strong antimicrobial activity against Escherichia coli K99, a major livestock pathogen. In this study, we aimed to investigate the antimicrobial activity of phthalyl pullulan nanoparticle (PPN)-treated LP. Interestingly, when PPNs were added to LP, the PPNs were internalized into the LP through an energy-dependent and galactose transporter-dependent mechanism. Additionally, more plantaricin, a natural antibacterial peptide, was secreted from PPN-treated LP than from untreated or pullulan-treated LP. Furthermore, antimicrobial activity against Gram-negative Escherichia coli K99 and Gram-positive Listeria monocytogenes by PPN-treated LP was higher than those of untreated or pullulan-treated LP. It is thought that the enhanced antimicrobial properties of the PPN-treated LP are due to intracellular stimulation. Overall, this research provides a new method of producing plantaricin in LP through intracellular stimulation by internalized PPNs

Suppression of tobacco carcinogen-induced lung tumorigenesis by aerosol-delivered glycerol propoxylate triacrylate-spermine copolymer/short hairpin Rab25 rna complexes in female A/J mice

Background: Rab25, a member of Rab family of small guanosine triphosphatase, is associated with progression of various types of human cancers, including lung cancer, the leading cause of cancer-associated deaths around the globe. Methods: In this study, we report the gene therapeutic effect of short hairpin Rab25 RNA (shRab25) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in female A/J mice. Initially, mice (6 weeks old) were injected with single dose of NNK (2mg/0.1mL saline/mouse) by intraperitoneal injection to induce the tumor. Eight weeks later, shRab25 was complexed with glycerol propoxylate triacrylate-spermine (GPT-SPE) copolymer and delivered into tobacco-induced lung cancer models through a nose-only inhalation system twice a week for 2 months. Results: GPT-SPE/shRab25 largely decreased the tobacco-induced tumor numbers and tumor volume in the lungs compared to GPT-SPE- or GPT-SPE/shScr-delivered groups. Remarkably, aerosol-delivered GPT-SPE/shRab25 significantly decreased the expression level of Rab25 and other prominent apoptosis-related proteins in female A/J mice. The apoptosis in these mice was determined by detecting the expression level of Bcl-2, proliferating cell nuclear antigen, Bax, and further confirmed by TUNEL assay. Conclusions: Our results strongly confirm the tumorigenic role of Rab25 in tobacco carcinogen-induced lung cancer and hence demonstrate aerosol delivery of shRab25 as a therapeutic target for lung cancer treatment.

Progress of tissue adhesives based on proteins and synthetic polymers

In recent years, polymer-based tissue adhesives (TAs) have been developed as an alternative to sutures to close and seal incisions or wounds owing to their ease of use, rapid application time, low cost, and minimal tissue damage. Although significant research is being conducted to develop new TAs with improved performances using different strategies, the applications of TAs are limited by several factors, such as weak adhesion strength and poor mechanical properties. Therefore, the next-generation advanced TAs with biomimetic and multifunctional properties should be developed. Herein, we review the requirements, adhesive performances, characteristics, adhesive mechanisms, applications, commercial products, and advantages and disadvantages of proteins- and synthetic polymer-based TAs. Furthermore, future perspectives in the field of TA-based research have been discussed.This was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Minister of Education (NRF-2020R11A1A1053275)

Superparamagnetic Iron Oxide Nanoparticles Coated with Galactose-Carrying Polymer for Hepatocyte Targeting

Our goal is to develop the functionalized superparamagnetic iron oxide nanoparticles (SPIONs) demonstrating the capacities to be delivered in liver specifically and to be dispersed in physiological environment stably. For this purpose, SPIONs were coated with polyvinylbenzyl-O-β-D-galactopyranosyl-D-gluconamide (PVLA) having galactose moieties to be recognized by asialoglycoprotein receptors (ASGP-R) on hepatocytes. For use as a control, we also prepared SPIONs coordinated with 2-pyrrolidone. The sizes, size distribution, structure, and coating of the nanoparticles were characterized by transmission electron microscopy (TEM), electrophoretic light scattering spectrophotometer (ELS), X-ray diffractometer (XRD), and Fourier transform infrared (FT-IR), respectively. Intracellular uptake of the PVLA-coated SPIONs was visualized by confocal laser scanning microscopy, and their hepatocyte-specific delivery was also investigated through magnetic resonance (MR) images of rat liver. MRI experimental results indicated that the PVLA-coated SPIONs possess the more specific accumulation property in liver compared with control, which suggests their potential utility as liver-targeting MRI contrast agent

Suppression of lung cancer progression by biocompatible glycerol triacrylate–spermine-mediated delivery of shAkt1

Background: Polyethylenimine (PEI)-based nonviral gene-delivery systems are commonly employed because of their high transfection efficiency. However, the toxic nature of PEI is a significant obstacle in clinical gene therapy. In this study, we developed biocompatible glycerol triacrylate-spermine (GT-SPE) polyspermine as a nanosized gene carrier for potential lung cancer gene therapy. Methods: The GT-SPE was synthesized using the Michael addition reaction between GT and SPE. The molecular weight was characterized using gel permeability chromatography multiangle laser light scattering and the composition of the polymer was analyzed using proton nuclear magnetic resonance. Results: The GT-SPE successfully protected the DNA from nucleases. The average particle size of the GT-SPE was 121 nm with a zeta potential of +23.45 mV. The GT-SPE was found to be less toxic than PEI for various cell lines, as well as for a murine model. Finally, our results showed that the GT-SPE/small hairpin Akt1 (shAkt1) complex suppressed lung tumorigenesis in a K-ras(LA1) lung cancer mice model by inducing apoptosis through the Akt signaling pathway and cell cycle arrest. Aerosol delivered GT-SPE/shAkt1, which reduced matrix metalloproteinase-9 activity and suppressed the expression levels of proliferating cell nuclear antigen, as well as vascular endothelial growth factors and CD31, which are known proliferation and angiogenesis markers, respectively. Conclusion: Our data suggest that GT-SPE may be a candidate for short hairpin-shaped RNA-based aerosol lung cancer gene therapy

Abdominal pain without bruising or sign of trauma: pancreatic injuries in children is difficult to predict

Pancreatic injuries due to trauma in children are rare. An early diagnosis is difficult as the signs and symptoms are insidious, but delays in diagnosis can lead to significant complications. We report a case of a child who visited the emergency department with aggravating abdominal pain. The physicians first diagnosed the abdominal pain as being caused by a disease in the emergency department, but the patient was subsequently diagnosed with pancreatic injury. Clinicians should be aware of a possible trauma in children who complain of vague abdominal pain even in the absence of corresponding history

Effect of microencapsulation of egg yolk immunoglobulin Y by sodium alginate/chitosan/sodium alginate on the growth performance, serum parameters, and intestinal health of broiler chickens

Objective Egg yolk immunoglobulin (IgY) is an antibiotic alternative to prevent and fight intestinal pathogenic infections. This study aimed to investigate the effects of sodium alginate/chitosan/sodium alginate IgY microcapsules on the growth performance, serum parameters, and intestinal health of broiler chickens. Methods One-day-old broilers (Ross 308) were divided into five treatments, each with 10 replicates of five chickens. The dietary treatments were maintained for 28 days and consisted of a basal diet (NC), basal diet + 500 mg chlortetracycline/kg diet (CH), basal diet + 50 mg non-microencapsulated IgY/kg diet (NM), basal diet + 600 mg low levels microencapsulated IgY/kg diet (LM), and basal diet + 700 mg high levels microencapsulated IgY/kg diet (HM). Results Throughout the 28-day trial period, the NM, LM, HM, and CH groups increased average daily gain compared with the NC group (p<0.05), and the HM group reduced feed conversion ratio compared with the CH group (p<0.05). The LM and HM groups increased relative organ weights of thymus and spleen compared with the CH and NM groups (p< 0.05). The HM group improved the duodenal, jejunal and ileum villi height (VH) and villus height to crypt depth ratio (VH:CD) compared with the CH and NM groups (p<0.05). Compared with the CH group, the HM group increased serum immunoglobulin (IgA), immunoglobulin G (IgG), superoxide dismutase, total antioxidant capacity, and glutathione peroxidase levels (p<0.05), and decreased serum malondialdehyde levels (p<0.05). Compared with the NC group, the NM, LM, HM, and CH groups reduced colonic Escherichia coli and Salmonella levels (p<0.05). and the HM group promoted the levels of lactic acid bacteria and bifidobacteria compared with the CH group (p<0.05). Conclusion Microencapsulation could be considered as a way to improve the efficiency of IgY. The 700 mg high levels microencapsulated IgY/kg diet could potentially be used as an alternative to antibiotics to improve the immune performance and intestinal health, leading to better performance of broiler chickens