Objective To obtain the intestines absorption of TPGS-CS/PTX polymeric micelles in rats, a drug-loaded micelle system was established by a kind of amphiphilic copolymer, D-α-tocopherol polyethylene glycol 1000 succinate-chitosan (TPGS-CS) was prepared by grafting D-α-tocopherol polyethyleneglycol 1000 succinate (TPGS) as the donor of the micelle hydrophobic group on chitosan (CS) as bioadhesive material, and loading paclitaxel as model drug. Methods TPGS was activated by its hydroxy-terminal carboxylation with succinic anhydride (SA) and 4-dimethylaminopyridine (DMAP). The TPGS-CS copolymer was prepared by the amidation of free amino groups on CS. The chemical structure of the TPGS-CS grafted copolymer was characterized by Fourier transform-infrared spectroscopy (FT-IR) and Nuclear magnetic resonance spectroscopy (NMR). The polymer micelle loading paclitaxel was selected as model drug and TPGS-CS/PTX was prepared by ultrasonic emulsification method. The encapsulation efficacy (EE) and drug loading (DL) were determined by high performance liquid chromatography (HPLC). The particle size, Zeta potential, and size distribution of the micelle system were measured by dynamic light scattering (DLS). The surface morphology of the micelles was investigated by Transmission electron microscopy (TEM). The in vivo intestines absorption rate (Ka) of paclitaxel-loaded TPGS-CS micelle was calculated in rats. Results The results of FT-IR and 1H NMR indicated that the copolymer (TPGS-CS) was synthesized. The TEM result showed that the formed particles were uniform in shape without aggregation. The Ka of TPGS-CS/PTX was 20 percent higher in comparison to the reference preparation, it indicated that this polymeric micelles could increase bioavailability. Conclusion The proposed TPGS-CS copolymer was successfully synthesized in this experiment, and the drug-loaded micelles prepared by ultrasonic emulsification exhibited good characteristics compared with the reference preparation, the Ka of paclitaxel was increased to some extent to promote oral absorption of the drug.

Animals ; Herbicides ; poisoning ; Humans ; Paraquat ; poisoning

Anticoagulants ; poisoning ; Humans ; Male ; Middle Aged ; Rodenticides ; poisoning

Objective To analyze the possibility of using TCR Vβsubfamily as the diagnostic in-dicators for major histocompatibility complex( MHC) deficiency-induced graft-versus-host disease( GVHD) . Methods The BALB/c mice were given 9.5 Gy (950 rad) of irradiation and transplanted with 106 of T-cell depleted (TCD) bone marrow cells from C57BL/6 and DBA/2 mice with MHC Ⅱ deficiency.Two control groups were set up accordingly by injection of TCD bone marrow cells from wild type ( WT) C57BL/6 and DBA/2 mice.Several parameters including the body weight, the GVHD clinical score and the survival time of the recipients were monitored.Flow cytometry analysis and mixed lymphocyte culture test were performed for the evaluation of autoimmune responses.Histological examination was used to analyze the severity of GVHD.Results The MHC deficiency-induced GVHD was successfully induced in the irradiated BALB/c mice receiving MHC mismatched allogeneic hematopoietic cell transplantation ( allo-HCT ) . The MHC matched DBA/2 mice with MHC deficiency could be used as the mice model of subclinical GVHD.Changes of the TCR Vβ6 were consistent with the results of histopathological examination.Conclusion Highly ex-pressed TCR Vβ6 could be used as indicators for the diagnosis of MHC deficiency-induced subclinical GVHD.

Diagnosis, Differential ; Endothelium, Vascular ; metabolism ; pathology ; Female ; Humans ; Hyperplasia ; Jejunal Diseases ; metabolism ; pathology ; surgery ; Jejunum ; blood supply ; pathology ; surgery ; Middle Aged ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism

Adult ; Carcinoma ; virology ; Cervical Intraepithelial Neoplasia ; virology ; Female ; Human papillomavirus 16 ; isolation & purification ; Human papillomavirus 18 ; isolation & purification ; Humans ; In Situ Hybridization ; Middle Aged ; Papillomavirus Infections ; Uterine Cervical Neoplasms ; virology

Objective To investigate the effects of 14-3-3 protein overexpression on the 1-methyl-4-phenylpyridinium (MPP(+)) induced pheochromocytoma (PC12) cell death and the potential mechanisms. Methods pcDNA3.1(+)-14-3-3 plasmids, which could be expressed in mammalian cell, were constructed and transfected into PC12 cells with Lipofectamine 2000. The expression of 14-3-3 protein, Bcl-2 protein, and BAD protein were determined by western blot. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, microplate reader, and flow cytometric analysis were used to measure cell viability, the caspase activity, and apoptotic ratio respectively. Results (1) The expression of 14-3-3 protein increased significantly three weeks after pcDNA3.1 (+)-14-3-3 plasmids transfected into PC12 cells. (2) MPP(+) caused a decrease of cell viability in a dose-dependent manner. At 100 mu mol/L MPP(+), cell viability reduced approximately 50%. (3) The caspase activity increased along with the MPP(+) concentrations rising and reached its maximum value (0.34 mu mol/mg protein) at 100 mu mol/L MPP(+). However caspase activity decreased significantly when the MPP(+) concentration exceeded 100 mu mol/L. (4) Overexpression of 14-3-3 protein decreased the apoptosis ratio of PC12 cells treated with 100 mu mol/L MPP(+) from 26.5% to 8.6%. (5) Bcl-2 protein tended to decrease but BAD protein tended to increase after treatment of PC12 cells with 100 mu mol/L MPP(+). Overexpression of 14-3-3 protein significantly increased the cellular level of Bcl-2 protein and decreased that of BAD protein. Conclusion Overexpression of 14-3-3 protein may reduce MPP(+)-induced apoptotic cell death in PC12 cells by up-regulating the Bcl-2 expression and down-regulating the BAD expression. These results may provide a promising target for treatment of Parkinson' s disease.

To investigate if glycogen synthase kinase 3 (GSK3) is involved in squamous differentiation of airway (tracheobronchial) epithelial cells, primary pig airway epithelial cells were treated with lithium chloride, a highly selective inhibitor of GSK3. Change in morphology of cells was monitored under microscopy, and expression of beta-catenin, phosphorylated GSK3 and involucrin, a squamous differentiation marker, were dectected by Western blotting, while expression of mRNA of another squamous differentiation marker, small proline-rich protein, was detected by RT-PCR. Further, luciferase reporter assay was used to assess the activation of beta-catenin/Tcf signaling. The results demonstrated that lithium was able to induce a squamous morphology of the cells, and to enhance the expression of involucrin and small proline-rich protein mRNA. Moreover, lithium increased inhibitory phosphorylation of GSK3, augmented nuclear translocation of beta-catenin in a dose- and time-dependent manner. Activation of beta-catenin/Tcf signaling was observed after the elevation of squamous differentiation markers. Taken together, these data suggest that GSK3 is possibly involved in squamous differentiation of pig airway epithelial cells.

OBJECTIVETo investigate the association between occupational psychological stress and metabolic syndrome (MS) in Hui and Han populations in Ningxia, China.

METHODSA 1:1 matched case-control study was performed. A total of 600 unrelated patients aged from 20 to 60 years who were clearly diagnosed with MS in General Hospital of Ningxia Medical University and Wuzhong People's Hospital from October 2011 to October 2012 were collected as the case group (MS group). A total of 600 healthy people who underwent a regular health examination in the same hospital during the same period were selected as the control group with matched gender, nationality, and age (≤ ± 3 years). The self-designed questionnaire was used to investigate the general situations and do the physical examination, and the fasting venous blood samples were collected for laboratory biochemical blood tests. The Occupational Stress Inventory (OSI) was used to investigate the subjects' occupational stress factors and stress levels.

RESULTSWith the increase in stress levels, the levels of WC, FPG, TG, AST, and UA were increased, WHR, SBP, and DBP first increased and then decreased, and the level of HDL-C increased. There were statistically significant differences in these parameters between the two groups (P < 0.05 or 0.01). The occupational psychological stress test results showed that the total score of stress factors (t = 6.676, P < 0.05), workload (t = 10.269, P < 0.05), interpersonal relationship (t = 6.569, P < 0.05), family/work balance (t = 2.028, P < 0.05), cognitive load (t = 8.714, P < 0.05), and other scores (t = 2.838, P < 0.05) in the MS group were all significantly higher than those in the control group, but there were no significant differences in the scores of management role, work responsibilities, and organizational climate between the MS group and the control group (P>0.05). There were no significant differences in the total score of stress factors and the score of each factor between Hui and Han groups (P>0.05). The relative risks of MS in the people with moderate stress exposure were 2.325 and 2.331 times those in the people with mild stress exposure before and after adjustment for age, gender, education level, marriage status, smoking, and drinking, and the relative risks for MS in the people with severe stress exposure were 3.000 and 3.126 times those in the people with mild stress exposure. There were significant differences in the detection rates of abdominal obesity, high TG, low HDL-C, hypertension, hyperglycemia, and diabetes between the sub-groups with different stress levels in the MS group (χ² = 17.636, 8.514, 14.640, 14.280, and 33.323, P < 0.01). The results of multivariate conditional logistic regression analysis showed that the risk factors for MS were SBP, TG, LDL-C, UA, BMI, fasting blood glucose, family history of hypertension, family history of diabetes, and the level of psychological stress in Ningxia, and the protective factor for MS was HDL-C.

CONCLUSIONThe occupational psychological stress is closely associated with MS, and it is an environmental risk factor for MS. With the increase in the stress level, the detection rates of MS components and the relative risk for MS are significantly increased. And there is no significant difference in the level of occupational psychological stress between the Hui and Han nationality groups.

Adult ; Asian Continental Ancestry Group ; ethnology ; Case-Control Studies ; China ; epidemiology ; Humans ; Hypertension ; Logistic Models ; Metabolic Syndrome ; epidemiology ; Middle Aged ; Occupational Diseases ; epidemiology ; Risk Factors ; Smoking ; Stress, Psychological ; epidemiology ; Surveys and Questionnaires ; Workload

OBJECTIVETo explore the difference between adolescent and adult C57BL/6J mice in response to rapid eye movement sleep (REMS) deprivation in terms of anxiety behavior and hippocampal NO level.

METHODSBoth adolescent and adult C57BL/6J mice were divided into normal control (NC) group, wide platform (WP) group, and 24-hour REMS deprivation group, each group consisting of 15 mice. REMS deprivation models were established using a small platform in water tank, and the elevated plus maze test was used to examine anxiety behavior of the mice. After behavioral tests, the mice were sacrificed to examine hippocampal NO levels using enzyme-linked immunosorbent assay, and hippocampal nNOS protein expression was detected with Western blotting.

RESULTSThe adolescent C57BL/6J mice showed no obvious differences in anxiety behaviors between the 3 groups, but NO level and nNOS expression in the hippocampus was significantly higher in REMSD group than in NC and WP groups (P<0.01). The adult mice in REMSD group, compared with those in the other two groups, exhibited significantly increased total number of arm entry (P<0.01), lowered number of open arm entry and reduced open arm time (P<0.01), increased number of close arm entry and prolonged close arm time (P<0.01 or 0.05); no obvious differences in NO level or nNOS expression in the hippocampus were found in the 3 groups of adult mice.

CONCLUSIONREMS deprivation produces different effects on anxiety-related behaviors between adolescent and adult mice possibly in relation to their different responses in terms of NO levels and nNOS expression in the hippocampus.

Animals ; Anxiety ; Hippocampus ; chemistry ; Mice ; Mice, Inbred C57BL ; Nitric Oxide ; chemistry ; Nitric Oxide Synthase Type I ; metabolism ; Sleep Deprivation ; Sleep, REM