Anti-depressant effect of curcumin-loaded guanidine-chitosan thermo-sensitive hydrogel by nasal delivery.

Curcumin, a polyphenol compound extracted from the roots of turmeric plants, possesses anti-depressant effect by regulating the levels of neuroendocrine immunological factors. The purpose of this study was to investigate the anti-depressant effect of curcumin through nasal delivery. The results of phase solubility, Fourier transform infrared spectra, Differential scanning calorimetry, X-ray powder diffractometry and 1H NMR spectra assays showed that curcumin/hydroxypropyl-ß-cyclodextrin complex had been obtained. The viscosity of hydrogel increased rapidly at the temperature range of 29-30 °C through the test of rheological property of Guanidine-Chitosan thermo-sensitive hydrogel. And the hydrogel had good mucoadhesion properties. The cumulative release rate of curcumin was 55% in 10 h in vitro drug release test. Curcumin-loaded (14.6, 29.2, or 58.4 µg/kg) thermo-sensitive hydrogel could reduce the immobility time of mice in force swimming test and tail suspension test, while could not increase the independent behavioral activity of mice. In addition, curcumin-loaded (14.6, 29.2, or 58.4 µg/kg) thermo-sensitive hydrogel could increase the concentration of Norepinephrine, Dopamine, 5-Hydroxytryptamine and their metabolites in hippocampus and striatum. In conclusion, thermo-sensitive hydrogel delivery system can be seen as a promising formulation of curcumin for the treatment of depression through nasal delivery.

[Meta-analysis on efficacy of salvianolate in prevention of contrast-induced nephropathy].

To systemically evaluate the efficacy and safety of salvianolate intravenous drip in combination with hydration against contrast-induced nephropathy( CIN),and guide clinical medication. Chinese and English databases( PubMed,EMbase,the Cochrane Library,CBM,VIP,Wan Fang database,CNKI) were retrieved to collect the randomized controlled trials( RCTs) about the efficacy of salvianolate intravenous drip in combination with hydration( trial group) vs routine hydration( control group) in the prevention of contrastinduced nephropathy. The methodological quality of the RCTs was evaluated by using the Cochrane 5. 1. 0 Bias Risks Assessment Tool.The data were extracted and Meta-analysis was conducted by Reviewer Manager 5. 3. Egger's test and non-parametric clipping method were used to evaluate publication bias. A total of 9 RCTs with 2 186 participants were included. RESULTS:: of Meta-analysis showed that the incidence of contrast-induced nephropathy of trial group was significantly higher than that of control group( RR = 0. 46,95% CI[0. 35,0. 59],P<0. 001). Subgroup analysis showed that the incidences of CIN in patients with acute coronary syndrome( ACS) undergoing PCI,in patients with the average age≥65 years,in patients who received mean contrast volume ≥200 m L,in patients with serum creatinine( Scr) ≥ 80 µmol,or in patients who received intraoperative administration of salvianolate or PCI were higher than those in control group,with statistically significant differences( P<0. 05). The experimental group was superior to the control group in improving the indexes of renal function after operation,and the difference was statistically significant( P<0. 05). No study reported the incidence of adverse reactions( ADRs). The funnel plots of the incidence of CIN showed potential publication bias. The results of Egger's linear regression showed that there was certain publication bias. Sensitivity analysis,funnel plot,and " trim and fill" showed that the results of this study were stable and reliable. Salvianolate combined with routine hydration showed definite clinical efficacy in the prevention of contrast-induced nephropathy. However,exact conclusion should be further verified by additional high-quality,multi-centre,and large-scale RCT studies.

A mathematical model for predicting putative association between E2/T ratio and the development of benign prostate hyperplasia in rats.

Benign prostatic hyperplasia (BPH) develops more likely with increasing age and changing serum concentrations of circulating estradiol (E2) and/or testosterone (T). In this study, we explored the relationship between serum E2/T ratio and BPH risk in rats by fitting a mathematical model. A total of 176 rats were randomized to one of the following treatment groups: normal control, castrated control, and 20 more groups of castrated animals treated with increasing dose combinations of T and E2, once daily for 30 days. Serial blood samples were obtained to determine serum T and E2 levels by magnetic bead enzyme-linked immunosorbent assay. Prostate tissue was taken to measure prostate volume. MATLAB software was used to simulate the relationship between prostate/body weight ratio (PBR) and E2/T ratio with a mathematical equation. The values of PBR, E2 and T in the treatment groups were significantly higher than those in the control groups. Stepwise regression showed that PBR was a function of E2 and T. PBR = -0.1782 + 0.0081 E2 + 0.063 T - 0.6 × 10-5 E22 - 0.28 × 10-3 T2. E2/T ratio change may be one of the risk factors for PBR, which is associated with the development of BPH.

Pharmacodynamic study of 131I-labeled CA215 antibody on an animal model of estrogen-resistant OC-3-VGH ovarian cancer.

The aim of the present study was to explore the inhibitory effect of 131I-labeled ovarian cancer antigen 215 (131I-CA215) antibody on human OC-3-VGH ovarian cancer. A subcutaneous transplanted tumor model of estrogen-resistant human OC-3-VGH ovarian cancer in nude mice was established. The model mice were randomly divided into seven groups, which were the negative control (NC), positive control (PC; 60 mg/kg cyclophosphamide), high-dose CA215 antibody (HA; 10 mg/kg), low-dose CA215 antibody (LA; 2 mg/kg), high-dose 131I-CA215 antibody (131I-HA; 10 mg/kg + 125 µCi), medium-dose 131I-CA215 antibody (131I-MA; 6 mg/kg + 75 µCi) and low-dose 131I-CA215 antibody (131I-LA; 2 mg/kg + 25 µCi) groups. Each group received intraperitoneal administration for 14 consecutive days. At 24 h after the final administration, the tumor was removed and weighed to calculate the tumor inhibition rate (TIR) and the relative tumor increase rate (T/C). Compared with the NC group, the HA group, as well as the 31I-HA and 131I-MA antibody groups, exhibited significantly inhibited tumor growth. The relative T/C values were 54, 30 and 48%, respectively, and the TIRs were 33.59, 64.89 and 45.80%, respectively. All differences were statistically significant. The difference between the HA and 131I-HA groups also presented statistical significance. CA215 and 131I-CA215 antibodies can markedly inhibit OC-3-VGH ovarian cancer. The high-dose 131I-CA215 antibody demonstrated a clear synergetic effect.

Oral exposure to low-dose bisphenol A aggravates testosterone-induced benign hyperplasia prostate in rats.

The declining level of androgen during aging, associated with an inclining level of estrogen, has been hypothesized to be important in the development of benign prostatic hyperplasia (BPH). Within physiologic range, increasing estrogen levels can stimulate prostate to develop and permanently increase prostate size. As an estrogenic endocrine disruptor, bisphenol A (BPA) might be stimulatory to prostate development. We further hypothesized that low dose BPA could induce hyperplasia prostate to proliferate and aggravate the symptom of BPH in male SD rats. BPH was induced by testosterone and then treated with BPA (10, 30, or 90 µg/kg, i.g., daily), 17ß-estradiol (E(2); 50.0 µg/kg, s.c., daily), or vehicle for 4 weeks. We found that weight and volume in rats treated with low dose BPA (10 µg/kg) was higher than that of model control, and BPA significantly increased the relative weight of prostate (p < 0.01). For prostate lobes, BPA 10 µg/kg/day significantly increased relative weight of ventral prostate (VP), weight and relative weight of dorsolateral prostate (DLP) (p < 0.05). And histopathology results showed that height of epithelial cell (HEC) of VP and DLP in BPA group were significantly higher than that of model control (p < 0.01). BPA could also decrease testosterone level and increase prostate-specific antigen level. E(2) treatment also showed an obvious effect on relative weight of VP and DLP, HEC, and hormone levels. We concluded that environment exposure to low dose of BPA may induce prostate to proliferate and aggravate testosterone-induced benign hyperplasia prostate in rats.

Mitosis orientation in prostate epithelial cells changed by endocrine effect.

AIM: The aim of the present study was to investigate the effect of androgen and estrogen on mitosis orientation in the prostate epithelial cells of male rats. METHODS: Castrated rats were treated with a single injection of testosterone propionate (TP) or benzogynestry (E2). There were 8 rats in the control group and TP-treated or E2-treated group. Prostate, liver, a specimen of skin, and a segment of the jejunum and colon were removed after the corresponding treatment. The results were observed through immunohistochemistry and iron hematoxylin-eosin staining. RESULTS: All mitoses found in the prostate epithelial cells of castrated rats with TP were oriented parallel to the basement membrane; however, mitoses found in the prostate epithelial cells of castrated rats in E2 and the control group were oriented perpendicular to the basement membrane. TP treatment resulted in marked changes in mitosis orientation in the prostate epithelial cells. Bromodeoxyuridine-labeled positive cells could be seen throughout the stroma and prostate epithelial cells with an injection of TP; however, the positive cells could only be seen in the stroma of prostate with an injection of E2, and the positive cells could hardly be seen in the control group. CONCLUSION: We found a novel effect of TP in the prostate as a marked change of mitosis orientation in prostate epithelial cells.