RESUMEN

The intractable toxicity of cationic polymers limits their applicability in gene transport and controlled release. In consideration of the good biocompatibility and biofunctionality of dextran, herein we design and synthesize two types of amino group-containing cationic copolymers based on dextran by the copolymerization of cationic monomers from dextran backbones. Additionally, allyl crosslinkers containing disulfide bonds were introduced into polymerization, that made the copolymer crosslinked by disulfide. The resultant coacervates were formed from the self-assembly of cationic coplymers and anionic genes, and redox-responsive disulfide branch points endow coacervates with reducing environment responsiveness. The in vitro experiments showed that the dextran-based coacervates were sensitive to the reducing environment and underwent cleavage, which resulted in an effective release, uptake, and transfection of the genes by 293T cells. In addition, dextran-based coacervates can be used to carry siRNA into cancer cells with a high transfection efficiency, demonstrating their potential applicability in treatment against cancer.

Asunto(s)

Técnicas de Transferencia de Gen , Neoplasias/genética , Polímeros/química , ARN Interferente Pequeño/genética , Aniones/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Cationes/química , Proliferación Celular/genética , Dextranos/química , Disulfuros/química , Células HEK293 , Humanos , Neoplasias/terapia , Oxidación-Reducción , Polímeros/farmacología , ARN Interferente Pequeño/farmacología , Transfección

RESUMEN

Objective@#To investigate the expression and clinical significance of exosomal miR-1231 in plasma of pancreatic cancer (PC) patients and pancreatic cancer cells.@*Methods@#A total of 16 patients who were diagnosed with pancreatic cancer in Hunan Cancer Hospital were collected from April 2016 to August 2017. Meanwhile, 16 healthy volunteers were recruited as the healthy control group at the same period. The plasma exosomes were extracted, and the levels of miR-1231 were detected by qRT-PCR in PC and healthy control groups. Moreover, the clinicopathological significance of exosomal miR-1231 expression was analyzed. Furthermore, the expression of exosomal miR-1231 was detected in several pancreatic cancer cells (MIA PaCa-2, PANC-1, SW1990, AsPC-1 and BxPc-3) and two normal pancreatic epithelial cells (HPDE and human primary pancreatic epithelial cell).@*Results@#qRT-PCR results showed that the expression level of miR-1231 in plasma exosomes of pancreatic cancer patients (1.06±0.46) was significantly lower than that in healthy controls (2.30±0.99; P<0.05). The levels of exosomal miR-1231 in patients with stage Ⅰ-Ⅱ (1.515±0.531), no distant metastasis (1.236±0.461) and no lymph node metastasis (1.337±0.522) were significantly higher than those with stage Ⅲ-Ⅳ (0.848±0.224), distant metastasis (0.757±0.278) and lymph node metastasis (0.838±0.261), respectively (P<0.05 for all). In addition, there were no correlation between exosomal miR-1231 expression and age, sex, smoking history, CA19-9 levels and tumor sites (P>0.05). Furthermore, the expression level of exosomal miR-1231 in pancreatic cancer cell lines (0.142±0.135) was significantly lower than that in normal epithelial cells (1.127±0.179; P<0.05).@*Conclusions@#The downregulation of exosomal miR-1231 in plasma of pancreatic cancer patients and pancreatic cancer cells suggests that it is related to the initiation and development of PC. It may be a new diagnostic and prognostic marker for PC.

RESUMEN

Objective Fluctuation of glucose levels is more likely to cause oxidative stress which contributes to the development of insulin resistance through activating c-Jun N-terminal kinase (JNK).Such antio xidants as vitamin C or vitamin E do not appear very helpful.Radix Astragali (RA) is an herbal medicine with antioxidative ability.The study was to explore whether RA would lower the risk of insulin resistance in diabetic rats.Methods Diabetic rats received RA,insulin or both RA and insulin after diabetes were induced in male Wistar rats.Serum levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNFα),advanced glycation endproducts(AGEs) levels in kidney,the expression of insulin receptor (IR),insulin receptor substrate 1 (IRS-1),p38 mitogen-activated protein kinase (MAPK),p-p38 MAPK,p-JNK,p-IRS-1 Ser307,and p-IRS-1 Tyr612 in skeletal muscles were determined.Results Compared to diabetic rats treated with insulin,the diabetic rats treated with both insulin and RA demonstrated significantly lower levels of IL-6,TNF-α and AGEs (P ＜ 0.05),significantly lower activation of p-p38 MAPK and JNK (P ＜0.05),significantly higher expressions of IRS-1 (P ＜0.05),p-IRS-1 Tyr612,and significantly lower expression of p-IRS-1 Ser307 (P ＜ 0.05).Conclusions RA can lower the risk of insulin resistance through fighting oxidative stress in diabetic rats.

RESUMEN

Hepatocellular carcinoma is one of the malignant tumors with highest mortality.Nuclear factor κB (NF-κB) as the mediator of many pathways,such as metabolic pathway,angiogenesis and adherence factor,is implicated in the onset and progression of hepatocellular carcinoma.Through the literature retrieval,the activity of NF-κB and its implication in the onset,progression,invasion and metastasis have been reviewed in the article.