High-glucose promotes proliferation of human bladder cancer T24 cells by activating Wnt/ß-catenin signaling pathway.

OBJECTIVE: Bladder cancer is the most prevalent genitourinary malignant disorder worldwide. We aimed to observe effects of high-glucose on bladder cancer proliferation and explore the associated mechanisms. MATERIALS AND METHODS: Human bladder cancer cell line, T24, was divided into Blank, Control (Ctrl), 10 mmol/l, 20 mmol/l and 30 mmol/l group. T24 cell proliferation was evaluated by using multiple table tournament (MTT) assay and colony formation analysis, respectively. Quantitative Real-time PCR (qRT-PCR) assay was employed to examine mRNA expression of Wnt-5a and ß-catenin. Meanwhile, Western blot assay was used to evaluate expression of Wnt-5a and ß-catenin protein. The linear regression analysis was utilized to analyze correlation between Wnt-5a/ß-catenin expression and T24 cell proliferation. RESULTS: High-glucose significantly enhanced proliferation of T24 cells compared to that of Blank and Ctrl group (p < 0.05). High-glucose significantly promoted colony formation of T24 cells compared to that of Blank and Ctrl group (p < 0.05). High-glucose significantly up-regulated Wnt-5a mRNA and protein expression compared to that of Blank and Ctrl group (p < 0.01). High-glucose significantly increased ß-catenin mRNA and protein expression compared to that of Blank and Ctrl group (p < 0.01). Effects of high-glucose on T24 cell proliferation were increased following with the enhanced glucose concentration. Wnt/ß-catenin signaling pathway molecules were correlated with colony formation of T24 cells (p < 0.05). CONCLUSIONS: High-glucose promoted the proliferation of T24 cells by activating the Wnt/ß-catenin signaling pathway. This study would provide the novel targets for bladder cancer therapy.

Genome-wide identification, phylogenetic relationships, and expression analysis of the carotenoid cleavage oxygenase gene family in pepper.

Carotenoid cleavage oxygenases (CCOs) are a family of dioxygenases, which specifically catalyze the cleavage of conjugated double bonds in carotenoids and apocarotenoids in plants. In this study, genome-wide analysis of CCO genes in pepper plants was performed using bioinformatic methods. At least 11 members of the CCO gene family were identified in the pepper genome. Phylogenetic analysis showed that pepper and tomato CCO genes could be divided into two groups (CCDs and NCEDs). The CCD group included five sub-groups (CCD1, CCD4, CCD7, CCD8, and CCD-like). These results indicate that there is a close genetic relationship between the two species. Sequence analysis using the online tool, Multiple Expectation Maximization for Motif Elicitation (MEME), showed that the CCO proteins comprise multiple conserved motifs, with 20 to 41 amino acids. In addition, multiple cis-acting elements in the promoter of CCO genes were identified using the online tool PlantCARE, and were found to be involved in light responsiveness, plant hormone regulation, and biotic and abiotic stresses, suggesting potential roles of these proteins under different conditions. RNA-seq analysis revealed that the CCO genes exhibit distinct patterns of expression in the roots, stems, leaves, and fruit. These findings suggest that the CCO genes have important roles in the vegetative and reproductive development of pepper plants.

Relationship between blood glucose fluctuation and macrovascular endothelial dysfunction in type 2 diabetic patients with coronary heart disease.

OBJECTIVE: To evaluate the relationship between blood glucose fluctuation and macrovascular dysfunction. PATIENTS AND METHODS: Eighty-eight type 2 diabetes mellitus (T2DM) patients with or without coronary heart disease (CHD) and 30 healthy control subjects were recruited. Glycosylated hemoglobin A1c (HbA1c), fasting insulin (FIns), and C-reaction protein (CRP) and some other general clinical variables were measured. A 72-hour continuous glucose monitoring (CGM) and brachial artery endothelium-dependent flow-mediated dilation (FMD) assessment were performed. The glucose excursion, MAGE (mean amplitude of glycemic excursions), LAGE (largest amplitude of glycemic excursions), MPPGE (mean postprandial glycemic excursions), MODD (absolute means of daily differences), and IAUC70 (incremental area under the curve below 70 mg/dl) during the CGM were analyzed. Correlations between the various variables were analyzed. RESULTS: Enhanced blood glucose fluctuation was observed in T2DM patients with CHD as compared to other participants. And blood glucose fluctuation was correlated with FMD, CRP and HOMA-IR. CONCLUSIONS: Blood glucose fluctuation is an important factor that affects inflammatory response and possibly induces CHD in T2DM patients.

Effects of osthole on isolated guinea pig heart atria.

AIM: To study the effects of osthole (Ost) on the isolated guinea pig atria and the relationship between Ost effect and Ca2+. METHODS: Contractions of left atria were induced by electric stimulations. The contractile amplitude of left atria pre- and post-treated with Ost was measured according to the cumulative concentration method, the drug being added at 15 min intervals, the pA2 or pD2' were calculated. It were measured that the effects of Ost to the positive staircase and to the post-rest potential enhancement. The contractile responses were recorded via an auto-equiolibration recording instrument. RESULTS: Ost 10-300 mumol.L-1 and Ver 0.1-30 mumol.L-1 decreased the contractile force and inhibited the isoprenaline-induced restoration of contractile response in the left atria rendered inexcitable by KCl 25 mmol.L-1. Ost and Ver antagonized the CaCl2- and isoprenaline-induced positive inotropic response noncompetively, the pD2' values to Ost were 4.41 +/- 0.13 and 4.90 +/- 0.15, to Ver were 6.53 +/- 0.22 and 6.91 +/- 0.17, respectively. Both of them inhibited the contraction of the left atrium and reversed the frequency-contraction response from positive to negative staircase in the higher dosage (500 and 1 mumol.L-1), but they showed only slight inhibitory effect on post-rest potentiation. CONCLUSION: Ost was similar to, but much less potent than Ver in inhibiting the isolated guinea pig atria.

[Effects of osthole on the isolated guinea-pig ileum and taeniae coli].

Effects of osthole (Ost) and verapamil (Ver) were investigated in the isolated guinea-pig ileum and taeniae coli. In the isolated guinea-pig ileum or taeniae coli, Ost and Ver were both found to inhibit the contractions induced by acetylcholine (ACh), histamine (His) and KCl in a dose-dependent manner; and noncompetitively antagonize the CaCl2 cumulative dose-response curves, with pD2 values of 4.41 +/- 0.15 and 7.0 +/- 0.2, respectively. Ost at dose of 100 mumol/L and Ver at 1 mumol/L inhibited CaCl2 0.2 mmol/L induced the contractions of the isolated guinea-pig taeniae coli, and the contractions can be abolished by adding CaCl2 2 mmol/L in Ca(2+)-free medium; both of them showed pronounced inhibitions on intracellular calcium-dependent contractions induced by ACh, but showing no effects on the extracellular calcium-dependent contractions. These results indicate that Ost has calcium antagonistic effect and is similar to Ver in mechanism.

[Main pharmacological roles and clinical curative effect of sanbi rebao].

Sanbi Rebao (contain 32 components, such as Radix Aconiti, Rhizoma Chuanxiong, Semen Strychni, Radix Glycyrrhizae, Radix Angelicae sinensis, Radix Ledebouriellae, Fructus Evodiae, borneolum syntheticum, etc.) had antagonistic action on the ear swollen response induced by croton oil and on the ear inflammation reaction caused by dimethylphenylene in mice. It could decrease significantly the response rate of turning its body induced by acetic acid, increase the pain threshold caused by warm, reduce the surface seepage of injure skin and accelerate the wound recovery. The above results showed Sanbi Rebao possessed the roles of dephlogisticate, analgesia and promoting wound recovery, Besides these, clinic research indicated that effective rate of Sanbi Rebao on pain or numbness caused by cold, damp and wind (rheumatism) was 97%.