Objective To investigate the changes in serum levels of nitric oxide ( NO) and endothelin ( ET) in type 2 diabetes patients with vascular complications, and to analyze the relationship between these levels and risk factors.Method We selected 98 cases of type 2 diabetes patients.Based on the grouping criteria, the patients were divided into diabetic patients with vascular complications ( group A,49 cases) and those without ( group B,49 cases) .In addition, 44 age-and body mass index-matched healthy cases were selected for control(group C).Height, weight, blood pressure, duration of diabetes, fasting blood glucose, hemoglobin A1c ( HbA1c), blood lipids, and serum levels of NO and ET-1 of all the patients were recorded.Results The NO levels of the two groups with diabetes mellitus were significantly lower than in group C[(43.87 ±12.05)and (53.29 ±11.75)μmol/L versus (66.08 ±16.48)μmol/L, P<0.01], while the ET-1 levels of the two groups with diabetes mellitus were significantly higher [(100.25 ±20.34) and (77.55 ±14.84) versus (53.62 ±8.40)ng/L, P<0.01] than those of the group C.The NO levels of group A were significantly lower than in group B [(43.87 ±12.05) versus (53.29 ±11.75)μmol/L, P<0.01].Moreover, the ET-1 levels of the group A were significantly higher than in group B [(100.25 ±20.34) versus (77.55 ±14.84)ng/L, P<0.01].Between the two diabetic groups, group A showed significantly higher systolic blood pressure(SBP), diastolic blood pressure(DBP), HbA1c, and course than group B (P<0.01).Correlation analysis showed a negative correlation between SBP, DBP, fasting blood glucose, HbA1c, and NO a positive correlation between high-density lipoprotein cholesterol ( HDL-C ) and NO, a negative correlation between HDL-C and ET-1, and a positive correlation between SBP,LDL-C, uric acid, fasting blood glucose, HbA1c, and ET-1.Conclusion The serum levels of NO and ET-1 in diabetic patients are evidently abnormal.Vascular endothelium injury will become more serious in patients with complications.Therefore, the serum levels of NO and ET-1 in diabetic patients are correlated with control of blood glucose, blood pressure, and blood lipid levels.

In this study, the buffering capacity of amphiphilic pH-sensitivity copolymer poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (PEOZ-CHMC) was evaluated. The ammonium sulfate gradient method was used to prepare doxorubicin hydrochloride (DOX x HCl)-loaded liposomes (DOX-L), and then the post-insertion method was used to prepare PEOZ-CHMC and polyethylene glycol-distearoyl phosphatidyl ethanolamine (PEG-DSPE) modified DOX x HCl-loaded liposomes (PEOZ-DOX-L and PEG-DOX-L). The physico-chemical properties, in vitro drugs release behavior, cellular toxicity and intracellular delivery of liposomes were evaluated, separately. The results showed that PEOZ-CHMC has a satisfactory buffering capacity. The sephadex G-50 column centrifugation method and dynamic light scattering were used to determine the encapsulation efficiency (EE) and particle size of liposomes. The EE and particle size of DOX-L were (97.3 ± 1.4) % and 120 nm, respectively, and the addition of PEOZ-CHMC or PEG-DSPE had no influence on EE and particle size. The zeta potentials of three kinds of liposomes were negative. The release behavior of various DOX liposomes in vitro was investigated by dialysis method. In phosphate buffer solution (PBS) at pH 7.4, DOX x HCl was released from PEOZ-DOX-L in a sustained manner. While in PBS at pH 5.0, the release rate of DOX x HCl from PEOZ-DOX-L increased significantly, which suggested DOX x HCl was released from PEOZ-DOX-L in a pH-dependent manner. The intracellular delivery of liposomes was investigated by confocal laser scanning microscopy (CLSM). The CLSM images indicated that PEOZ-DOX-L showed efficient intracellular trafficking including endosomal escape and release DOX x HCl into nucleus, as well as the DOX-L and PEG-DOX-L had no this effect. The cytotoxicity of liposomes against MCF-7 cells was detected by using MTT assay. The results showed that antiproliferative effects of PEOZ-DOX-L enhanced with pH value decreased, whereas DOX-L and PEG-DOX-L did not have any significant difference in inhibitions at different pH conditions. Therefore, the problems of the inhibition of cellular uptake of liposomes and the failed endosomal escape of pH-sensitive liposomes by PEG chain can be overcome by the pH-sensitive liposomes constructed by PEOZ-CHMC.

Objective To investigate the effects of tongue cancer resistance-associated protein 1 (TCRP1) in proliferation of chronic myeloid leukemia cells (CML),and explore the new thoughts of pathogenesis of CML.Methods The expression of TCRP1 was detected in the peripheral blood mononuclear cells (PBMC) of CML with real-time quantitative polymerase chain reaction (PCR) and Western blot.After the expression of TCRP1 was interfered in K562 cells,the proliferation of cells was detected by 3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and soft agar colony forming assay,and the expression of protein kinase B (AKT) and its phosphorylation were tested by Western blot.Results In PBMC of CML patients,the mRNA and protein levels of TCRP1 were significantly higher than those of normal controls.The results of MTS assay and soft agar colony forming assay showed that the proliferation of K562 cells was significantly decreased after the expression of TCRP1 was interfered.After knockdown of TCRP1 in K562 cells,the phosphorylation of AKT was significantly decreased while the expression of total AKT did not change.Conclusions The expression of TCRP1 was increased in CML cells.High expression of TCRP1 might contribute to proliferation of K562 cells via the phosphorylation of AKT.

Humans ; Neutrophils ; Receptors, Cell Surface ; GPI-Linked Proteins ; HIV Infections ; Isoantigens

Drug-metabolizing enzymes (DMEs), a diverse group of enzymes responsible for the metabolic elimination of drugs and other xenobiotics, have been recognized as the critical determinants to drug safety and efficacy. Deciphering and understanding the key roles of individual DMEs in drug metabolism and toxicity, as well as characterizing the interactions of central DMEs with xenobiotics require reliable, practical and highly specific tools for sensing the activities of these enzymes in biological systems. In the last few decades, the scientists have developed a variety of optical substrates for sensing human DMEs, parts of them have been successfully used for studying target enzyme(s) in tissue preparations and living systems. Herein, molecular design principals and recent advances in the development and applications of optical substrates for human DMEs have been reviewed systematically. Furthermore, the challenges and future perspectives in this field are also highlighted. The presented information offers a group of practical approaches and imaging tools for sensing DMEs activities in complex biological systems, which strongly facilitates high-throughput screening the modulators of target DMEs and studies on drug/herb‒drug interactions, as well as promotes the fundamental researches for exploring the relevance of DMEs to human diseases and drug treatment outcomes.