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.

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.

[Expression of HIF-1α in the prostatic tissue of mice with high-fat diet-induced obesity].

OBJECTIVE: To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in the prostatic tissue of mice with high-fat diet-induced obesity and to explore the effect of hypoxia on BPH in obese male mice. METHODS: We randomly divided 20 C57BL/6J male mice into two groups of equal number and fed them on a high-fat diet (HFD group) or a normal diet (control group) for 17 weeks. Then, we measured the body weight, prostate weight, prostate volume and levels of serum triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and free fatty acids (FFA) by ELISA, observed the morphology of the prostate by HE staining, calculated the area of the prostatic glandular cavity, and determined the expression of HIF-1α in the prostatic tissue by immunohistochemistry. RESULTS: Compared with the controls, the mice fed on the HFD showed significant increases in the body weight (ï¼»28.94 ± 2.17ï¼½ vs ï¼»42.55 ± 3.01ï¼½ g, P < 0.01), prostate weight (ï¼»0.05 ± 0.03ï¼½ vs ï¼»0.13 ± 0.03ï¼½ g, P < 0.01), prostate volume (ï¼»0.05 ± 0.02ï¼½ vs ï¼»0.14 ± 0.03ï¼½ ml, P < 0.01), and the levels of TG (ï¼»115.77 ± 25.25ï¼½ vs ï¼»179.29 ± 65.19ï¼½ mmol/L, P = 0.022), HDL (ï¼»67.14 ± 3.10ï¼½ vs ï¼»72.84 ± 1.91ï¼½ g/L, P < 0.01) and LDL (ï¼»44.16 ± 7.24ï¼½ vs ï¼»66.88 ± 1.93ï¼½ g/L, P < 0.01) at 17 weeks. Histopathological examination exhibited single-layer cuboidal or columnar prostatic epithelium in the controls but an irregular epithelial structure and a larger area of the prostatic glandular cavity in the HFD group (ï¼»12 390 ± 8 587ï¼½ vs ï¼»18 453 ± 7 311ï¼½ µm2, P < 0.01). The integrated optical density (IOD) of HIF-1α was markedly higher in the HFD group (ï¼»9.1 ± 6.9ï¼½ × 106) than in the control (ï¼»2.0 ± 3.6ï¼½ ×106) (P < 0.01). The prostate volume was positively correlated with the body fat weight (r = 0.887, P = 0.01), TG (r = 0.520, P = 0.047) and LDL (r = 0.772, P = 0.010). CONCLUSIONS: Abnormal lipid metabolism may induce local hypoxia in the prostate tissue and lead to BPH in obese mice.

[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.

Contour integration deficits at high spatial frequencies in children treated for anisometropic amblyopia.

Purpose: This study was conducted to reexamine the question of whether children treated for anisometropic amblyopia have contour integration deficits. To do so, we used psychophysical methods that require global contour processing while minimizing the influence of low-level deficits: visibility, shape perception, and positional uncertainty. Methods: Thirteen children with anisometropic amblyopia (age: 10.1 ± 1.8 years) and thirteen visually normal children (age: 10.8 ± 2.0 years) participated in this study. The stimuli were closed figures made up of Gabor patches either in noise or on a blank field. The contrast thresholds to detect a circular contour on a blank field, as well as the thresholds of aspect ratio and contour element number to discriminate a circular or elliptical contour in noise, were measured at Gabor spatial frequencies of 1.5, 3, and 6 cpd for amblyopic eyes (AEs), fellow eyes (FEs), and normal control eyes. Visual acuities and contrast sensitivity functions for AEs and FEs and the Randot stereoacuity were measured before testing. Results: The AEs showed contrast deficits and degraded shape perception compared to the FEs at higher spatial frequencies (6 cpd). When the influence of abnormal contrast sensitivity and shape perception were minimized, the AEs showed contour integration deficits at spatial frequencies 3 and 6 cpd. These deficits were not related to basic losses in contrast sensitivity and acuity, stereoacuity, and visual crowding. Besides, no significant difference was found between the fellow eyes of the amblyopic children and the normal control eyes in the performance of contour integration. Conclusion: After eliminating or compensating for the low-level deficits, children treated for anisometropic amblyopia still show contour integration deficits, primarily at higher spatial frequencies, which might reflect the deficits in global processing caused by amblyopia. Contour integration deficits are likely independent of spatial vision deficits. Refractive correction and/or occlusion therapies may not be sufficient to fully restore contour integration deficits, which indicates the need for the development of clinical treatments to recover these deficits.

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.

Dichoptic Perceptual Training in Children With Amblyopia With or Without Patching History.

Purpose: Dichoptic training is becoming a popular tool in amblyopia treatment. Here we investigated the effects of dichoptic demasking training in children with amblyopia who never received patching treatment (NPT group) or were no longer responsive to patching (PT group). Methods: Fourteen NPT and thirteen PT amblyopes (6-16.5 years; 24 anisometropic, two strabismus, and one mixed) received dichoptic demasking training for 17 to 22 sessions. They used the amblyopic eye (AE) to practice contrast discrimination between a pair of Gabors that were dichoptically masked by a band-filtered noise pattern simultaneously presented in the fellow eye (FE). Dichoptic learning was quantified by the increase of maximal tolerable noise contrast (TNC) for AE contrast discrimination. Computerized visual acuities and contrast sensitivity functions for both eyes and the Randot stereoacuity were measured before and after training. Results: Training improved maximal TNC by six to eight times in both groups, along with a boost of AE acuities by 0.15 logMAR (P < 0.001) in the NPT group and 0.06 logMAR (P < 0.001) in the PT group. This visual acuity improvement was significantly dependent on the pretraining acuity. Stereoacuity was significantly improved by 41.6% (P = 0.002) in the NPT group and 64.2% (P < 0.001) in the PT group. The stereoacuity gain was correlated to the pretraining interocular acuity difference (r = -0.49, P = 0.010), but not to the interocular acuity difference change (r = -0.28, P = 0.15). Training improved AE contrast sensitivity in the NPT group (P = 0.009) but not the PT group (P = 0.76). Moreover, the learning effects in 12 retested observers were retained for 10 to 24 months. Conclusions: Dichoptic training can improve, and sometimes even restore, the stereoacuity of amblyopic children, especially those with mild amblyopia (amblyopic VA ≦0.28 logMAR). The dissociation of stereoacuity gain and the interocular acuity difference change suggests that the stereoacuity gain may not result from a reduced interocular suppression in most amblyopes. Rather, the amblyopes may have learned to attend to, or readout, the stimulus information to improve stereopsis.

Diaqua-bis(5-carb-oxy-2-propyl-1H-imidazole-4-carboxyl-ato-κN,O)magnesium(II) 3.5-hydrate.

In the title complex, [Mg(C(8)H(9)N(2)O(4))(2)(H(2)O)(2)]·3.5H(2)O, the Mg(II) atom is six-coordinated by two N,O-bidentate 5-carb-oxy-2-propyl-1H-imidazole-4-carboxyl-ate ligands and two water mol-ecules, forming a distorted octa-hedral environment. The complex mol-ecules are linked into a three-dimensional network by N-H⋯O and O-H⋯O hydrogen-bonding inter-actions. The propyl groups are disordered over two sites, with site occupancies of 0.755 (7):0.245 (7) and 0.556 (13):0.444 (13).

Bis(nitrato-κO)(5,7,12,14-tetra-methyl-1,4,8,11-tetra-aza-cyclo-tetra-decane-6,13-diaminium-κN,N,N,N)copper(II) dinitrate tetra-hydrate.

In the title compound, [Cu(NO(3))(2)(C(14)H(36)N(6))](NO(3))(2)·4H(2)O, the Cu(II) atom, lying on an inversion center, is six-coordinated in a distorted octa-hedral environment by four N atoms from a centrosymmetric 14-membered tetra-aza-cyclo-tetra-decane macrocyclic ligand and two O atoms from two nitrate anions. The supra-molecular network is consolidated by extensive O-H⋯O and N-H⋯O hydrogen-bonding inter-actions.

Repair mechanism of astrocytes and non-astrocytes in spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a destructive disease that incurs huge personal and social costs, and there is no effective treatment. Although the pathogenesis and treatment mechanism of SCI has always been a strong scientific focus, the pathogenesis of SCI is still under investigation. AIM: To determine the key genes based on the modularization of in-depth analysis, in order to identify the repair mechanism of astrocytes and non-astrocytes in SCI. METHODS: Firstly, the differences between injured and non-injured spinal cord of astrocyte (HA), injured and non-injured spinal cord of non-astrocyte (FLOW), injured spinal cord of non-injured astrocyte (HA) and non-injured spinal cord of non-astrocyte (FLOW), and non-injured spinal cord of astrocyte (HA) and non-astrocyte (FLOW) were analyzed. The total number of differentially expressed genes was obtained by merging the four groups of differential results. Secondly, the genes were co-expressed and clustered. Then, the enrichment of GO function and KEGG pathway of module genes was analyzed. Finally, non-coding RNA, transcription factors and drugs that regulate module genes were predicted using hypergeometric tests. RESULTS: In summary, we obtained 19 expression modules involving 5216 differentially expressed genes. Among them, miR-494, XIST and other genes were differentially expressed in SCI patients, and played an active regulatory role in dysfunction module, and these genes were recognized as the driving genes of SCI. Enrichment results showed that module genes were significantly involved in the biological processes of inflammation, oxidation and apoptosis. Signal pathways such as NF-kappa B/A20, AMPK and MAPK were significantly regulated. In addition, non-coding RNA pivot (including miR-136-5p and let-7d-5p, etc.) and transcription factor pivot (including NFKB1, MYC, etc.) were identified as significant regulatory dysfunction modules. CONCLUSION: Overall, this study uncovered a co-expression network of key genes involved in astrocyte and non-astrocyte regulation in SCI. These findings helped to reveal the core dysfunction modules, potential regulatory factors and driving genes of the disease, and to improve our understanding of its pathogenesis.

Dichoptic De-Masking Learning in Adults With Amblyopia and Its Mechanisms.

Purpose: Recently, we reported that dichoptic de-masking training can further boost stereoacuity, but not visual acuity, in adults with amblyopia after extensive monocular perceptual training. Here, we investigated whether this dichoptic training targets on interocular suppression directly, or improves vision through high-level brain mechanisms. Methods: Eleven adults with amblyopia first used amblyopic eyes (AEs) to perform contrast (n = 6) or orientation (n = 5) discrimination training, while resisting dichoptic noise masking from fellow eyes (FEs). Learning was indicated by increased maximal tolerable noise contrast (TNC) for AE contrast/orientation discrimination. After dichoptic training, six observers continued to use AEs to perform monocular training for nine sessions. Results: (1) Training of dichoptic de-masking doubled maximal TNC, but learning did not transfer much to the same task at an orthogonal orientation or a different task, showing orientation/task specificities. (2) Following a training-plus-exposure (TPE) protocol, AEs then received exposure of the orthogonal orientation by performing the other orientation/contrast discrimination task at the orthogonal orientation. After this TPE training, dichoptic learning with the original discrimination task transferred to the orthogonal orientation. (3) Dichoptic training improved AE's acuity (1.2 lines), stereoacuity (60.2%), and contrast sensitivity (mainly at higher spatial frequencies). (4) Additional monocular training did not produce further acuity and stereoacuity gains. Conclusions: The initial orientation/task specificities exclude the possibility that dichoptic training reduces physiological interocular suppression. The later transfer of learning to an orthogonal orientation with TPE training suggests improvement in high-level brain processing. Dichoptic training may strengthen top-down attention to AEs to counter the impacts of attentional bias to FEs and/or physiological interocular suppression and improve stereoacuity.

Dichoptic training in adults with amblyopia: Additional stereoacuity gains over monocular training.

Dichoptic training is a recent focus of research on perceptual learning in adults with amblyopia, but whether and how dichoptic training is superior to traditional monocular training is unclear. Here we investigated whether dichoptic training could further boost visual acuity and stereoacuity in monocularly well-trained adult amblyopic participants. During dichoptic training the participants used the amblyopic eye to practice a contrast discrimination task, while a band-filtered noise masker was simultaneously presented in the non-amblyopic fellow eye. Dichoptic learning was indexed by the increase of maximal tolerable noise contrast for successful contrast discrimination in the amblyopic eye. The results showed that practice tripled maximal tolerable noise contrast in 13 monocularly well-trained amblyopic participants. Moreover, the training further improved stereoacuity by 27% beyond the 55% gain from previous monocular training, but unchanged visual acuity of the amblyopic eyes. Therefore our dichoptic training method may produce extra gains of stereoacuity, but not visual acuity, in adults with amblyopia after monocular training.

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.

Correlation between exposure to magnetic fields and embryonic development in the first trimester.

OBJECTIVE: To explore the correlation between maternal magnetic field (MF) exposure in daily life and embryonic development. METHODS: A cross-sectional study was conducted among 149 pregnant women who were seeking induced abortion of unwanted pregnancies. Participating women were asked to wear an EMDEX Lite magnetic field meter for a 24-h period to obtain MF exposure level within 4 weeks following the abortion. Embryonic bud and sac lengths were measured through B-mode ultrasound before the surgical abortion. Embryo sections were prepared and examined for histological changes, and the apoptosis status of the deciduas was examined using the TUNEL apoptosis assay. RESULTS: Embryonic bud length was inversely associated with maternal daily MF exposure level; the association was statistically significant at the time-weighted-average and 75th percentile of MF exposure levels, with coefficients of -3.09 (P = 0.0479) and -3.07 (P = 0.0228), respectively. Logistic regression for examining the risk of higher MF exposure indicated that women with her 75th percentile of daily MF measurements ≥0.82 mG had a 3.95-fold risk of having a fetus with a shorter embryonic bud length than those whose daily MF exposure were <0.82 mG. MF exposure was associated with a higher degree of apoptosis, but the association was not statistically significant. We failed to find a statistical correlation between MF exposure and embryonic sac length and histological changes in the first trimester. CONCLUSION: Prenatal MF exposure may have an adverse effect on embryonic development.

The therapeutic impact of perceptual learning on juvenile amblyopia with or without previous patching treatment.

PURPOSE: To investigate the therapeutic impact of perceptual learning on juvenile amblyopia that is no longer responsive to patching treatment (PT group) or was never patch treated (NPT group). METHODS: Ten PT and 13 NPT subjects aged 8 to 17 years were trained with a grating acuity task for 40 to 60 sessions. Half in each group were further trained with single or crowded tumbling E acuity tasks for 8 to 10 sessions. RESULTS: Training improved grating acuity by -2.1% in the PT eyes and 36.1% in the NPT eyes, along with a boost of single and crowded E acuities by 0.9 or 0.7 lines in the PT eyes and 1.5 and 1.2 lines in the NPT eyes, in contrast to a nearly 5-line improvement in the same PT eyes after previous patching treatment. Stereoacuity was improved in some PT and NPT eyes. The single and crowded E acuity improvements were not significantly dependent on the pretraining acuity. The single and crowded E acuity and stereoacuity improvements were uncorrelated with grating acuity improvement, suggesting some random training impacts on different tasks and individuals. Further direct single and crowded E acuity training generated an additional 0.2- and 0.2-line boost for PT eyes and a 0.4- and 0.5-line boost for NPT eyes, resulting in overall single and crowded E acuity gains of 1.4 and 1.0 lines for PT eyes and 2.2 and 1.8 lines for NPT eyes. CONCLUSIONS: Perceptual learning has a small but significant therapeutic impact on both PT and NPT juvenile eyes, which is most likely to have clinical values for eyes with mild amblyopia. Early diagnosis and treatment are most important and effective.

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.