脂多糖对胆汁分泌的影响

[目的 ]通过脂多糖对胆汁分泌的影响实验 ,初步探讨引起肝功能障碍及肝内结石形成的机理 .[方法 ]在麻醉状态下 ,直接往实验动物肝内注入脂多糖等实验药物 ,测定相关数据 .[结果 ]脂多糖对胆汁分泌有抑制作用 ,并对胆汁酸、磷脂浓度有降低作用 ,而对胆红素、钙的浓度无显著作用 .[结论 ]脂多糖对胆汁分泌有明显作用 ,对诱发肝功能障碍及形成肝内胆结石有一定的影响     

Microglandular Adenosis

Microglandular adenosis (MGA) of the breast is a very rare and benign proliferative lesion. Most patients complain of a palpable breast mass that may arouse a clinical suspicion of breast cancer. Histopathologically, it is hard to distinguish MGA from breast cancer because of the lack of a myoepithelial layer and infiltrative proliferation. Several studies have reported a strong relationship between MGA and carcinoma arising in MGA, so the mass should be excised completely in cases of MGA determined from a core needle biopsy rather than observation. A 72-years-old woman presented with a palpable breast mass. On physical examination, a mass was palpable in the right upper outer quadrant area and somewhat fixed to the surrounding tissues and pectoralis major muscle. We could not detect any mass or dense lesion on mammography because of a grade 4 dense breast. Ultrasonographic findings revealed a low echoic lesion with indistinct margins. The result of a core needle biopsy was MGA, which was confirmed by excision. We report one case of MGA, which was believed to breast cancer clinically.     

Water-Soluble and Low Molecular Weight Chitosan-Based Plasmid DNA Delivery

Purpose. Chitosan, a natural cationic polysaccharide, is a candidate non-viral vector for gene delivery because of its high positive charges and low cytotoxicity. In this study, low molecular weight chitosan (LMWC, molecular weight of 22 kDa) was characterized and evaluated as a gene carrier. Methods. Plasmid/LMWC complex was analyzed in 1% agarose gel electrophoresis. To confirm that the LMWC protected plasmids from nuclease, DNase I protection assays were performed. pSV--galactosidase plasmid/LMWC complex was transfected into 293T cells and transfection efficiency was evaluated by -galactosidase assay. Cytotoxicity of LMWC was determined by MTT assay. Results. Unlike high molecular weight chitosan (HMWC), LMWC is highly water soluble, and can form complex with plasmids in physiological buffer. The plasmid DNA was completely retarded at a weight ratio of 1:2 (plasmid:LMWC) in 1% agarose gel. DNase I protection assay showed that plasmids were protected from DNase I over 60 min. The most efficient transfection was obtained at a weight ratio of 1:3 (plasmid:LMWC). The transfection efficiency of LMWC was significantly higher than naked DNA and higher than poly-L-lysine (PLL). MTT assay showed that LMWC was less cytotoxic than PLL. Conclusions. LMWC is non-toxic and has higher transfection efficiency than PLL. Therefore, LMWC will be useful in the development of safe gene carriers.     

Paclitaxel interrupts TGF-beta1 signaling between gallbladder epithelial cells and myofibroblasts

BACKGROUND: The cellular and molecular mechanisms of fibrogenesis in the extrahepatic biliary epithelium are not known. Transforming growth factor-beta1 (TGF-beta1) is a cytokine implicated in signaling pathways that mediate collagen formation. An observation that paclitaxel (PT), applied topically into the rat common bile duct, inhibited stricture formation led us to hypothesize that PT's effects might be due to interruption of TGF-beta1 signaling between biliary epithelial cells and subepithelial myofibroblasts. MATERIALS AND METHODS: We tested this hypothesis using an in vitro cell-culture model in which murine gallbladder epithelial cells (GBEC) are cultured separately or cocultured with human gallbladder myofibroblasts (GBMF). RESULTS: Exposure to Escherichia coli lipopolysaccharide (LPS) enhanced TGF-beta1 mRNA expression and stimulated TGF-beta1 protein secretion into both apical and basolateral compartments in GBEC. This effect was more prominent with basolateral secretion and was also more pronounced in the coculture system. In GBMF, collagen I mRNA expression and protein secretion were stimulated by treatment with LPS or TGF-beta1. GBMF also expressed TGF-beta1 mRNA, whose levels were enhanced by exposure to either LPS or exogenous TGF-beta1. PT inhibited LPS-induced TGF-beta1 mRNA expression and protein secretion in GBEC in both culture systems. Tumor necrosis factor-alpha mRNA expression and protein secretion were not affected by PT in GBEC, demonstrating that the effects were specific for TGF-beta1. PT also inhibited LPS- and TGF-beta1-induced collagen I mRNA expression and protein secretion in GBMF. CONCLUSIONS: These findings support a model in which GBEC communicate with subepithelial GBMF via TGF-beta1, leading to collagen deposition and fibrosis, and in which GBMF possess autocrine mechanisms involving TGF-beta1 that could regulate collagen production. PT inhibits these fibrogenic pathways.     

Chitosan-graft-polyethylenimine as a gene carrier.

Chitosans have been proposed as biocompatible alternative cationic polymers that are suitable for non-viral delivery. However, the transfection efficiency of chitosan-DNA nanoparticles is still very low. To improve transfection efficiency, we prepared chitosan-graft-polyethylenimine (CHI-g-PEI) copolymer by an imine reaction between periodate-oxidized chitosan and polyethylenimine (PEI). The molecular weight and composition of the CHI-g-PEI copolymer were characterized, using multi-angle laser scattering (GPC-MALS) and (1)H nuclear magnetic resonance ((1)H NMR), respectively. The copolymer was complexed with plasmid DNA (pDNA) in various copolymer/DNA (N/P) charge ratios, and the complex was characterized. CHI-g-PEI showed good DNA binding ability and high protection of DNA from nuclease attack. Also, with an increase in charge ratio, the sizes of the CHI-g-PEI/DNA complex showed a tendency to decrease, whereas the zeta potential of the complex showed an increase. The CHI-g-PEI copolymer had low cytotoxicity, compared to PEI 25K from cytotoxicity assays. At high N/P ratios, the CHI-g-PEI/DNA complex showed higher transfection efficiency than PEI 25K in HeLa, 293T and HepG2 cell lines. Our results indicate that the CHI-g-PEI copolymer has potential as a gene carrier in vitro.     

Clonazepam release from poly(DL-lactide-co-glycolide) nanoparticles prepared by dialysis method

Aim of this work is to prepare poly(DL-lactide-co-glycolide) (PLGA) nanoparticles by dialysis method without surfactant and to investigate drug loading capacity and drug release. The size of PLGA nanoparticles was 269.9±118.7 nm in intensity average and the morphology of PLGA nanoparticles was spherical shape from the observation of SEM and TEM. In the effect of drug loading contents on the particle size distribution, PLGA nanoparticles were monomodal pattern with narrow size distribution in the empty and lower drug loading nanoparticles whereas bi- or trimodal pattern was showed in the higher drug loading ones. Release of clonazepam from PLGA nanoparticles with higher drug loading contents was slower than that with lower loading contents.     

Novel approach of molecular genetic understanding of iridology: relationship between iris constitution and angiotensin converting enzyme gene polymorphism

Iridology is the study of the iris of the eye to detect the conditions of the body and its organs, genetic strengths and weaknesses, etc. Although iridology is not widely used as a scientific tool for healthcare professionals to get to the source of people's health conditions, it has been used as a supplementary source to help the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris among some Korean Oriental medical doctors. Angiotensin converting enzyme (ACE) gene polymorphism is one of the most well studied genetic markers of vascular disease. We investigated the relationship between iridological constitution and ACE polymorphism in hypertensives. We classified 87 hypertensives and 79 controls according to iris constitution and determined the ACE genotype of each individual. DD genotype was more prevalent in patients with a neurogenic constitution than in controls. This finding supports the hypothesis that D allele is a candidate gene for hypertension and demonstrates the association among ACE genotype, Korean hypertensives and iris constitution.     

Emotional Distress of the COVID-19 Cluster Infection on Health Care Workers Working at a National Hospital in Korea

BackgroundFrontline healthcare workers responding to coronavirus disease 2019 (COVID-19) inevitably face tremendous psychological burden. Thus, the present study aimed to identify the psychological impact and the factors contributing to the likely increase in emotional distress of healthcare workers.MethodsThe participants include a total of 99 healthcare workers at Bugok National Hospital. Psychometric scales were used to assess emotional distress (12-item General Health Questionnaire; GHQ-12), depression symptoms (Patient Health Questionnaire-9; PHQ-9), and post-traumatic stress disorder-related symptoms (Impact of Events Scale-Revised; IES-R). A supplementary questionnaire was administered to investigate the experience of healthcare workers exposed to COVID-19-infected patients. Based on the results of GHQ-12 survey, participants were categorized into two groups: distress and non-distress. All the assessed scores were compared between the two groups. A logistic regression model was constructed to identify factors associated with emotional distress.ResultsEmotional distress was reported by 45.3% (n = 45) of all participants. The emotionally distressed group was more likely to be female, manage close contacts, have higher scores on PHQ-9 and IES-R, feel increased professional risk, and report that proper infection control training was not provided. Female gender, managing close contacts, higher scores on PHQ-9, and a feeling that proper infection control training was not provided were associated with emotional distress in logistic regression.ConclusionFrontline healthcare workers face tremendous psychological burden during the COVID-19 pandemic. Therefore, appropriate psychological interventions should be provided to the HCWs engaged in the management of COVID-19-infected patients.     

Fabrication of a Novel Core-Shell Gene Delivery System Based on a Brush-Like Polycation of α, β–Poly (L-Aspartate-Graft-PEI)

Purpose  A novel core-shell gene delivery system was fabricated in order to improve its gene transfection efficiency, particularly in the presence of serum. Materials and Methods  α, β–poly (L-aspartate-graft-PEI) (PAE) was simply synthesized by ring-opening reaction of poly (L-succinimide) with low molecular weight (LMW) linear polyethylenimine (PEI, Mn = 423). PAE/DNA nanoparticles were characterized. Condensation and protection ability of plasmid by PAE were confirmed by agarose gel electrophoresis assay. Cytotoxicity of the polymer and polymer/DNA nanoparticles were measured by MTS assay. Gene transfection efficiencies were evaluated both in vitro and in vivo. Results  Core-shell nanoparticles assembled between DNA and PAE showed positive zeta potential, narrow size distribution, and spherical compact shapes with size below 250 nm when N/P ratio is above 10. Cytotoxicity of PAE was rather lower than that of PEI 25K, while the most efficient gene transfection and serum resistant ability of PAE/DNA complexes were higher than that of PEI 25K. Bafilomycin A1 treatment suggested “proton sponge” mechanism of PAE-mediated gene transfection. PAE/pEGFP-N2 nanoparticles also showed good gene expression in vivo and were dominantly distributed in kidney, liver, spleen and lung after intravenous administration. Conclusions  The results demonstrated the potential use of PAE as an effective gene carrier. J.-H. Yu and J.-S. Quan have contributed equally to this work.     

Poly (amino ester) Composed of Poly (ethylene glycol) and Aminosilane Prepared by Combinatorial Chemistry as a Gene Carrier

Purpose Application of combinatorial chemistry and high throughput screening for the synthesis and evaluation of mini-library of novel biodegradable poly (β-amino ester)s (PAE)s composed of γ-aminopropyl-triethoxysilane (APES) and poly (ethylene glycol) diacrylate (PEGDA) for gene delivery efficiency and safety in 293T and HeLa cells in the presence of and absence of serum. Materials and methods PAEs were synthesized at different mole ratios of APES and PEGDA by Michael addition reaction and synthesis was confirmed by ¹H nuclear magnetic resonance (¹H-NMR). Ninety six ratios of polyplexes were evaluated for luciferase and MTS assay in 293T and HeLa cells in the presence of and absence of serum. Relationship between transfection efficiency and DNA binding ability of PAEs was studied by gel electrophoresis. Particle sizes and molecular weight of selected PAEs were measured by dynamic light scattering and gel permeation chromatography multi-angle light scattering, respectively. Results ¹H-NMR confirmed the synthesis of PAEs. In both cell lines, transfection efficiency and cell viability were increased for PAEs obtained from R106 (0.7:1, APES:PEGDA) to R121 (6:1, APES:PEGDA) with a marginal increase in APES concentration. Transfection pattern was uniform in the absence of and presence of serum. In both cell lines, PAE obtained from R121 demonstrated high transfection efficiency and low cytotoxicity as compared to polyethylenimine (25 KDa) and Lipofectamine. PAE obtained from R121 showed good DNA binding and condensation with average particle sizes of 133 nm. Conclusion Addition of PEGDA over APES resulted in a novel PAE which has high safety and transfection efficiency. Transfection and cytotoxicity are very sensitive to monomer ratios and mainly governed by concentration of amine monomer.